阅读说明：本技术 用于液晶应用的生物可获得的手性掺杂剂 (Biologically available chiral dopants for liquid crystal applications ) 是由 A·萨菲尔 S·拉贾 A·佐姆贝尔特 R·J·特威格 P·尼泊尔 A·维迪奇-费尔南多 于 2019-12-06 设计创作，主要内容包括：本公开内容讨论了用于液晶材料的手性掺杂剂。手性掺杂剂可为生物可获得的化合物,即由微生物通过发酵产生的化合物。手性掺杂剂还可包括通过化学合成步骤进一步修饰的生物可获得的材料。本文所讨论的手性掺杂剂可包括生物分子,例如甘草次酸(1)、S-柚皮素(2)、莽草酸(3)、α-水芹烯(4)、桦木醇(5)、苹果酸(6)、瓦伦烯(7)或诺卡酮(8),及其任何立体异构体或化学修饰的衍生物。本公开内容进一步示出了此类化合物在液晶材料中的光学特性。(The present disclosure discusses chiral dopants for liquid crystal materials. The chiral dopant may be a biologically available compound, i.e. a compound produced by a microorganism by fermentation. Chiral dopants may also include biologically available materials that are further modified by chemical synthesis steps. Chiral dopants discussed herein may include biomolecules such as glycyrrhetinic acid (1), S-naringenin (2), shikimic acid (3), alpha-phellandrene (4), betulin (5), malic acid (6), valencene (7), or nootkatone (8), and any stereoisomers or chemically modified derivatives thereof. The present disclosure further illustrates the optical properties of such compounds in liquid crystal materials.)

1. A chiral dopant selected from the following structures:

wherein R is₁、R₂、R₃And R₄Independently for each occurrence selected from the group consisting of hydrogen, aliphatic moieties, aryl moieties, arylalkylene moieties, alkylarylene moieties, alkanoyl moieties, arylalkanoyl moieties, and any halogenated derivatives of the foregoing; wherein Z is selected from C (H) R₅、-CR₅＝CR₅-, O, S or NR₅Wherein R is₅Independently selected for each occurrence from hydrogen, aliphatic moieties, aryl moieties, arylalkylene moieties, alkylarylene moieties, alkanoyl moieties, arylalkanoyl moieties and any halogenated derivatives of the foregoing.

2. The chiral dopant of claim 1, selected from structures (I), (II), (III), (IV), (V), (VI), (VII), or (VIII).

3. The chiral dopant of any one of the preceding claims, wherein R₁、R₂、R₃、R₄And R₅Independently selected for each occurrence from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, phenyl, benzyl, p-tolyl, p-halophenyl, p-diphenyl, p- (4-halophenyl) phenylene, p- (4-cyanophenyl) phenylene, o-diphenyl, 3, 5-dimethoxyphenyl, acetyl, propionyl, butyryl, pentanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, 1-naphthyl, or 2-naphthyl.

4. A liquid crystal material comprising at least one chiral dopant according to claim 1.

5. The liquid crystal material of claim 4, wherein the at least one chiral dopant is present in an amount of at least 0.001 wt%, at least 0.002 wt%, at least 0.005 wt%, at least 0.01 wt%, at least 0.02 wt%, at least 0.05 wt%, at least 0.1 wt%, at least 0.2 wt%, at least 0.5 wt%, at least 1 wt%, at least 1.2 wt%, at least 1.5 wt%, at least 2 wt%, at least 2.5 wt%, at least 3 wt%, at least 3.5 wt%, at least 4 wt%, at least 4.5 wt%, at least 5 wt%, at least 6 wt%, at least 7 wt%, at least 8 wt%, at least 9 wt%, or at least 10 wt%, based on the weight of the liquid crystal material.

6. The liquid crystal material of claim 4, wherein the at least one chiral dopant is present in an amount no greater than 20 wt.%, no greater than 18 wt.%, no greater than 16 wt.%, no greater than 14 wt.%, no greater than 12 wt.%, no greater than 10 wt.%, or no greater than 8 wt.%, based on the weight of the liquid crystal material.

7. The liquid crystal material of claim 4, further comprising at least one polymerizable mesogenic compound having at least one polymerizable functional group.

8. The liquid crystal material of claim 7, wherein the polymerizable functional group comprises epoxy, vinyl, allyl, acrylate, methacrylate, isoprenyl, alpha-aminocarboxylate, or any combination thereof.

9. The liquid crystal material of claim 4, further comprising a nematic or nematic species.

10. A liquid crystal material according to claim 9 wherein the nematic or nematic species is selected from the group consisting of azoxybenzene, benzylideneaniline, biphenyl, terphenyl, phenyl benzoate, cyclohexyl benzoate, phenyl ester of cyclohexanecarboxylic acid, cyclohexyl ester of cyclohexanecarboxylic acid, phenyl ester of cyclohexylbenzoic acid, cyclohexyl ester of cyclohexylbenzoic acid, phenyl ester of cyclohexylcyclohexanecarboxylic acid, cyclohexyl ester of cyclohexylcyclohexanecarboxylic acid, cyclohexylphenyl ester of benzoic acid, cyclohexylphenyl ester of cyclohexanecarboxylic acid, cyclohexylphenyl ester of cyclohexylcyclohexanecarboxylic acid, phenylcyclohexane, cyclohexylbiphenyl, phenylcyclohexylcyclohexane, cyclohexylcyclohexane, cyclohexylcyclohexene, 1, 4-bis-cyclohexylbenzene, 4 '-bis-cyclohexylbiphenyl, phenylpyrimidine, cyclohexylpyrimidine, phenylpyridine, terphenyl, phenyl benzoate, cyclohexylphenyl benzoate, cyclohexyl ester of cyclohexanecarboxylic acid, phenylcyclohexane carboxylic acid, phenylcyclohexane, cyclohexylcyclohexane, cyclohexylcyclohexene, 1, 4' -bis-cyclohexylbenzene, phenylpyrimidine, cyclohexylpyrimidine, phenylpyridine, and the like, Cyclohexylpyridine, phenylpyridazine, cyclohexylpyridazine, phenyldioxane, cyclohexyldioxane, phenyl-1, 3-dithiane, cyclohexyl-1, 3-dithiane, 1, 2-diphenylethane, 1, 2-dicyclohexylethane, 1-phenyl-2-cyclohexylethane, 1-cyclohexyl-2- (4-phenylcyclohexyl) ethane, 1-cyclohexyl-2-biphenylethane, 1-phenyl-2-cyclohexylphenylethane, halogenated 1, 2-diphenylethylene, benzylphenyl ether, tolane, substituted cinnamic acid or any combination thereof.

11. A liquid crystal display, optical element, or color filter comprising the chiral dopant of claim 1.

12. A display comprising a layer of a liquid crystal material according to claim 4, the liquid crystal having a cholesteric pitch (P) and a thickness (d), wherein the ratio d/P is at least 0.01, at least 0.02, at least 0.05, at least 0.1 or at least 0.15.

13. A display comprising a layer of liquid crystal material according to claim 10, wherein the ratio d/P is no greater than 1, no greater than 0.8, no greater than 0.6, no greater than 0.4, no greater than 0.3, or no greater than 0.25.

Technical Field

The present invention relates generally to the field of optically active dopants, and more particularly to chiral dopants derived from biological sources.

Background

Electromagnetic (EM) radiation is ubiquitous and includes X-rays that pass through ultraviolet, visible, infrared, radio frequency, and low frequency waves. Protection of personnel and equipment from harmful radiation is an indispensable task. At optical frequencies, optical filters are used for this purpose. There are two types of optical filters: (i) an absorption filter that absorbs harmful radiation, and (ii) an interference filter that reflects rather than absorbs. Interference filters are preferred in many applications because absorption of radiation can lead to damage and failure. The interference filter is typically a layered structure that reflects light from each interface as follows: so that propagating waves destructively interfere and cancel, while reflected waves constructively interfere and substantially all incident light is reflected without damaging the filter.

Interference filters are expensive, mainly due to the complex processing required to build the precise layered structure. Cholesteric liquid crystals are chiral liquids that self-assemble into such periodic structures.

Furthermore, the interlayer spacing and optical properties of the self-assembled structure can be controlled by the external field. Cholesteric liquid crystals are therefore well suited for optical filter applications. They are used in displays, cosmetics, paints, coatings, chemical sensors, laser cavities and other photonic devices.

Due to the great inherent potential, cholesteric filters for eye and other sensor protection are currently being developed. However, material improvements are needed before effective practical devices can be realized. The filter may be static, having fixed optical properties; or may be agile (agile) in which the filters may be switched on or off, or in which the filters may be tuned to different wavelengths. Static filters require very high contrast, very low insertion loss, and relative insensitivity to temperature changes. In addition, the flexible filters also require switchability and/or tunability. These characteristics are already present in cholesteric liquid crystals, but they require higher performance levels, such as response speed, efficiency of elimination. These performance levels can be achieved by efficiently designing and producing improved materials.

Chiral nematic, also known as cholesteric, liquid crystal materials are useful in a variety of applications, including various liquid crystal (e.g., LC) displays, electronic writers or tablets, electronic skins, reflective films, optical filters, polarizers, coatings, and inks, among others. Methods for preparing such materials are well established. See, for example: g.gottarelli and g.spada, mol.cys.liq.cryst., 123,377 (1985); spada and G.Proni, Enantiomer,3,301 (1998); montbach et al, Proceedings of SPIE,7232,723203, (2009). However, improvements are still needed. While early uses of chiral nematic compositions relied on mixtures consisting primarily of chiral components, more recently such materials consist of nematic Liquid Crystal (LC) mixtures with small amounts of chiral dopants. In such new compositions, the properties of the nematic host material (such as, inter alia, viscosity, birefringence, electrical anisotropy and magnetic anisotropy) can be tailored to the desired application by changing the chemical composition of the nematic mixture, and then a chiral dopant is incorporated to induce helical twisting to provide the desired chiral nematic pitch. It is clear that the properties of such chiral nematic compositions are thus a combination of the properties of the nematic host plus the properties of the dopant.

Chiral nematic liquid crystals can be formulated to reflect incident electromagnetic radiation of various wavelengths, and it is well known that reflected light is circularly polarized, depending on the chiral sagittal (sense) direction of the helical pitch of the liquid crystal. Thus, a chiral nematic phase exhibiting a right-handed helical structure will reflect right-handed incident light. For many applications, right and left hand sagittal directions capable of reflecting circularly polarized light are useful, for example, in vertical layered structures. It is also well known that enantiomers of chiral dopant structures cause helical rotations of opposite polarity, thus providing reflection of light of opposite polarization. For this reason, it may be particularly useful to prepare pairs of dopant enantiomers for use in individual light modulation layers.

For some applications it is desirable to have a liquid crystal mixture that exhibits strong helical twist and thus has a short pitch length. Shorter pitches can be achieved by using higher amounts of dopants or by using dopants with higher helical twisting forces. However, the use of large amounts of chiral dopants has a negative effect on the properties of the liquid-crystalline host mixture: such as, inter alia, dielectric anisotropy, viscosity and drive voltage or switching time. In liquid crystal mixtures for selectively reflecting cholesteric displays, the pitch has to be chosen such that the maximum of the wavelength reflected by the cholesteric helix is in the visible range. Another possible application is a polymer film with a chiral liquid crystal phase for optical elements, such as cholesteric broadband polarizers or chiral liquid crystal retardation films.

Such liquid crystal materials can be used for the preparation of polymer films with a chiral liquid crystal phase, for active and passive optical elements or color filters and for liquid crystal displays, such as STN, TN, AMD-TN, temperature compensation, guest-host or phase change displays, or polymer-free or polymer-stabilized cholesteric texture (PFCT, PSCT) displays. Such a liquid crystal display may comprise a chiral dopant in a liquid crystal medium and a polymer film having a chiral liquid crystal phase, which polymer film is obtainable by (co) polymerizing a liquid crystal material containing the chiral dopant and a polymerizable mesogenic compound.

Biomolecules are suitable as chiral dopants because they are naturally available in high optical purity. However, these compounds are not readily available and designing a microorganism to overexpress a chiral molecule from tens of thousands of possible alternatives requires a good understanding of the desired properties.

The present disclosure describes the novel chiral dopants of the present invention from biologically available sources that provide these characteristics, can be easily prepared, have uniformly high helical twisting power, and do not have the drawbacks of the prior art dopants as described above.

Disclosure of Invention

In a first aspect, the chiral dopant may be selected from the following structures:

in the above structures (I) to (X), R, where applicable₁、R₂、R₃And R₄And for each occurrence is independently selected from the group consisting of hydrogen, aliphatic moieties, aryl moieties, arylalkylene moieties, alkylarylene moieties, alkanoyl moieties, arylalkanoyl moieties, and any halogenated derivatives of the foregoing.

The group Z may be selected from C (H) R₅、-CR₅＝CR₅-, O, S or NR₅Wherein R is₅Independently selected for each occurrence from hydrogen, aliphatic moieties, aryl moieties, arylalkylene moieties, alkylarylene moieties, alkanoyl moieties, arylalkanoyl moieties and any halogenated derivatives of the foregoing.

In a second aspect, the liquid crystal material can comprise at least one chiral dopant as shown in structures (I) to (X).

In a third aspect, a liquid crystal display, optical element, or color filter can comprise a chiral dopant as shown in structures (I) through (X).

In a fourth aspect, a display can include a layer of liquid crystal material containing a chiral dopant as shown in structures (I) through (X). The liquid crystal material may have a cholesteric pitch (P) and a thickness (d). In one embodiment, the ratio of d/P is at least 0.01, at least 0.02, at least 0.05, at least 0.1, or at least 0.15. In one embodiment, the liquid crystal material may comprise two, three, four, five or more chiral dopants.

Drawings

The present disclosure may be better understood, and its numerous features and advantages made apparent to those skilled in the art by referencing the accompanying drawings.

Fig. 1A shows liquid crystal molecules in an ellipsoidal form, which are aligned substantially in parallel in one direction in a nematic liquid.

FIG. 1B shows three independent twist modes in a nematic liquid crystal, each with its unique elastic constant.

FIG. 2A shows the selective reflection spectrum from a planar cholesteric liquid crystal structure, indicating that the efficiency and sharpness of the band edges gradually decrease with increasing applied electric field.

FIG. 2B is a schematic diagram of the planar structure of cholesteric liquid crystal, showing Bragg reflection of only one color.

FIG. 3 depicts the composition of nematic mixture E7.

Detailed Description

In a first aspect, the chiral dopant may be selected from the following structures:

in the above structures (I) to (X), R₁、R₂、R₃And R₄And for each occurrence is independently selected from the group consisting of hydrogen, aliphatic moieties, aryl moieties, arylalkylene moieties, alkylarylene moieties, alkanoyl moieties, arylalkanoyl moieties, and any halogenated derivatives of the foregoing.

The group Z may be selected from C (H) R₅、-CR₅＝CR₅-, O, S or NR₅Wherein R is₅Independently selected for each occurrence from hydrogen, aliphatic moieties, aryl moieties, arylalkylene moieties, alkylarylene moieties, alkanoyl moieties, arylalkanoyl moieties and any halogenated derivatives of the foregoing.

In one embodiment, the chiral dopant may be selected from structures (I), (II), (III), (IV), (V), (VI), (VII), or (VIII).

In another embodiment, the chiral dopant comprises the structures (I) through (X), wherein R is₁、R₂、R₃、R₄And R₅Independently selected from hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, phenylBenzyl, p-tolyl, p-halophenyl, p-diphenyl (p-biphenyl), p- (4-halophenyl) phenylene, p- (4-cyanophenyl) phenylene, o-diphenyl (o-biphenyl), 3, 5-dimethoxyphenyl, acetyl, propionyl, butyryl, pentanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, 1-naphthyl, 2-naphthyl.

In a second aspect, the liquid crystal material can comprise at least one chiral dopant as shown in structures (I) to (X).

In one embodiment, the liquid crystal material comprises at least one chiral dopant present in an amount of at least 0.001 wt%, e.g., at least 0.002 wt%, at least 0.005 wt%, at least 0.01 wt%, at least 0.02 wt%, at least 0.05 wt%, at least 0.1 wt%, at least 0.2 wt%, at least 0.5 wt%, at least 1 wt%, at least 1.2 wt%, at least 1.5 wt%, at least 2 wt%, at least 2.5 wt%, at least 3 wt%, at least 3.5 wt%, at least 4 wt%, at least 4.5 wt%, at least 5 wt%, at least 6 wt%, at least 7 wt%, at least 8 wt%, at least 9 wt%, or at least 10 wt%, based on the weight of the liquid crystal material.

In another embodiment, the liquid crystal material comprises at least one chiral dopant present in an amount of no greater than 20 wt.%, such as no greater than 18 wt.%, no greater than 16 wt.%, no greater than 14 wt.%, no greater than 12 wt.%, no greater than 10 wt.%, or no greater than 8 wt.%, based on the weight of the liquid crystal material. Further, in one embodiment, the chiral dopant may be present in an amount of 0.0015 to 17 weight percent, such as 0.01 to 15 weight percent, 0.05 to 13 weight percent, or 0.1 to 11 weight percent, based on the weight of the liquid crystal material.

In yet another embodiment, the liquid crystal material may further comprise at least one polymerizable mesogenic compound having at least one polymerizable functional group.

In one embodiment, the polymerizable functional group comprises epoxy, vinyl, allyl, acrylate, methacrylate, isoprenyl, alpha-aminocarboxylate, or any combination thereof.

In yet another embodiment, the liquid crystal material may comprise nematic or nematic (nematic) substances. In one embodiment, the nematic or nematic substance is selected from the group consisting of azoxybenzene, benzylideneaniline, biphenyl, terphenyl, phenyl benzoate, cyclohexyl benzoate, phenyl ester of cyclohexanecarboxylic acid, cyclohexyl ester of cyclohexanecarboxylic acid, phenyl ester of cyclohexanebenzoic acid, cyclohexyl ester of cyclohexanebenzoic acid, phenyl ester of cyclohexylcyclohexanecarboxylic acid, cyclohexyl ester of cyclohexylcyclohexanecarboxylic acid, cyclohexylphenyl ester of benzoic acid, cyclohexylphenyl ester of cyclohexanecarboxylic acid, cyclohexylphenyl ester of cyclohexylcyclohexanecarboxylic acid, phenylcyclohexane, cyclohexylbiphenyl, phenylcyclohexylcyclohexane, cyclohexylcyclohexane, cyclohexylcyclohexene, 1, 4-bis-cyclohexylbenzene, 4 '-bis-cyclohexylbiphenyl, phenylpyrimidine, cyclohexylpyrimidine, phenylpyridine, cyclohexylpyridine, phenylpyridazine, cyclohexylpyridine, phenylpyridazine, phenylcyclohexane, cyclohexylbenzene, 1, 4' -bis-cyclohexylbiphenyl, phenylpyrimidine, cyclohexylpyridine, and a mixture of phenylpyridazine and triphenylpyridine, triphenylamine, Cyclohexylpyridazine, phenyldioxane, cyclohexyldioxane, phenyl-1, 3-dithiane, cyclohexyl-1, 3-dithiane, 1, 2-diphenylethane, 1, 2-dicyclohexylethane, 1-phenyl-2-cyclohexylethane, 1-cyclohexyl-2- (4-phenylcyclohexyl) ethane, 1-cyclohexyl-2-diphenylethane, 1-phenyl-2-cyclohexylphenylethane, halogenated 1, 2-stilbenes, benzylphenyl ether, tolane, substituted cinnamic acids, or any combination thereof.

In a third aspect, a liquid crystal display, optical element, or color filter can comprise a chiral dopant as shown in structures (I) through (X).

In a fourth aspect, a display can include a layer of liquid crystal material containing a chiral dopant as shown in structures (I) through (X). The liquid crystal material may have a cholesteric pitch (P) and a thickness (d). In one embodiment, the ratio of d/P is at least 0.01, at least 0.02, at least 0.05, at least 0.1, or at least 0.15.

In one embodiment, the display layer of liquid crystal material comprises a ratio d/P of no greater than 1, no greater than 0.8, no greater than 0.6, no greater than 0.4, no greater than 0.3, or no greater than 0.25. In one embodiment, the ratio of d/P may be from 0.01 to 0.9, such as from 0.02 to 0.7, from 0.03 to 0.5, or from 0.04 to 0.4.

To make a "flexible filter device", a cholesteric (twisted nematic) medium is required. Such media must have a variety of physical properties, including a wide temperature cholesteric range (typically including ambient temperature) and distortion with minimal temperature dependence. The desired cholesteric medium can be produced in a number of ways. In this case, the medium is composed of molecules of mesomorphism and intrinsic chirality. The individual molecules that make up the medium contain one (pure enantiomers) or more (pure diastereomers) sites. It is also possible to mix different chiral nematic mesogens to create a medium with improved properties (care must be taken in the relationship between the chiral centres and the twisted sagittal direction produced by each component). If an enantiomer of a molecule is mixed with its mirror image, the twist will be reduced (a racemic mixture contains equal amounts of the two enantiomers and will appear to be achiral nematic). In this case, the medium is composed of mesogenic (nematic) molecules, but the molecules are not inherently chiral. Again, different achiral nematic seeding units (mesogens) can be mixed to create a medium with improved properties (but which will never be cholesteric). The achiral nematic host can be converted into a cholesteric medium by adding a twisting agent. Alternatively, cholesteric liquid crystals can be used as a twisting agent when mixed into an achiral nematic mesogenic unit.

Chiral twisting agent (dopant)

A twister is a chiral molecule (usually a pure enantiomer or diastereomer). The twist increases in direct proportion to the concentration by adding a twisting agent to the achiral nematic form. In many cases, the proportion of the twisting agent that can be added is limited by the solubility or loss of the mixture or the cholesteric temperature range.

The twisted cholesteric structure formed by the twisting agent is a self-assembled layered structure that functions as an interference filter. Light can be considered to consist of right-handed and left-handed circular polarization modes, where the electric field of the light rotates clockwise and counter-clockwise in space. Cholesteric structures produce destructive interference of forward propagating light and constructive interference of backward propagating light of a single chirality (handedness); resulting in substantially total reflection of one mode; cholesteric behaves like a perfect mirror-photonic bandgap in the selected wavelength range. The position and width of the band gap are determined by the refractive index of the nematic and the pitch of the cholesteric structure. The contrast is determined by the film thickness. Since the liquid crystal structure can be changed by an applied field, the filter can be switched on or off and its position and bandwidth can be adjusted. The polymer network can be used to stabilize the material to reduce scattering and increase speed. The biological acquisition of enantiomerically pure chiral compounds makes biomolecules excellent candidates for twisters for applications in cholesteric liquid crystal technology. Chemical modification of bioavailable materials, such as shown below, would be necessary to achieve new molecules with expected utility in liquid crystal technology. Derivatization is generally required to modify the polar functional groups in the original biological target material to make them physically more compatible (miscible) with the host nematic material (enhancing their interaction with the nematic component rather than with itself). Derivatization also provides some chemical stability enhancement. In the case of macromolecules (e.g. glycyrrhetinic acid), derivatization will also be of particular importance to lower the melting point and thereby increase the solubility of the additive in the host nematic form. The work reported herein describes the development of synthetic pathways that successfully derivatize the bioavailable species.

Scheme 1

As described in scheme 1, the dopant may include a biomolecule, such as glycyrrhetinic acid (1), S-naringenin (2), shikimic acid (3), α -phellandrene (4), betulin (5), malic acid (6), valencene (7), or nootkatone (8). Stereoisomers of the biomolecules are also included. For example, 3 β,18 β glycyrrhetinic acid (1 ') or R-naringenin (2') are also biomolecules within the scope of the invention described herein. The following structures show the general numbering of glycyrrhetinic acid esters and compound 1'.

In addition, other biological or chemical modifications of biomolecules are contemplated herein. Chemical modifications can produce ethers or esters, including small or large portions of saturated aliphatic, unsaturated aliphatic, saturated cycloaliphatic, unsaturated cycloaliphatic, aromatic, or combinations thereof. Likewise, a hydroxyl or keto group may be converted to an amine or imine by a substitution reaction or conjugation reaction, followed by reduction. The acid may be converted to an amide.

Other modifications include oxidation or reduction reactions. For example, primary alcohols may be converted to aldehydes or carboxylic acid groups, or secondary alcohols may be converted to ketone groups. As for reduction, the carboxyl group may be converted to a C-OH group or an ether group, and the carbon-carbon double bond may be reduced to a single bond.

In addition, other chemical modifications include reactions based on the nature of the pi bonds present in biomolecules. For example, α -phellandrene (as opposed to its β structural isomer) is a diene that undergoes a diels-alder reaction with a suitable dienophile (e.g., maleic anhydride) to enhance biomolecules having further modifiable moieties.

In yet another aspect, the biomolecule may be a starter molecule for larger dopants, e.g., malic acid is a diacid with one stereocenter. The diacid can be cyclized with an amine to form an imide that can contain groups suitable for liquid crystal dopant function.

Physical parameters of liquid crystal

The simplest form of liquid crystal is a nematic phase. The rod-shaped organic molecules are oriented on average in one direction, called director n (see fig. 1A). In the most stable state, n is the same anywhere in the volume. For example, by applying a voltage, the uniform distribution of n can be distorted very easily, but there are tiny bulletsAnd (4) a linear resistance. The Twist of n can always be divided into three independent modes, called "Splay", "Twist" and "Bend", as shown in fig. 1B. These modes have their own elastic constants: are each K₁₁、K₂₂And K₃₃. Understanding and designing the electro-optic response of liquid crystals is fundamental to understanding these elastic constants.

Most of the physical properties of liquid crystals depend on the direction relative to the average orientation of the molecules. The dielectric constant of the electric field parallel to the average orientation is ε₁The dielectric constant of the electric field perpendicular to the average orientation is ε₂. Some liquid crystals have epsilon₁>ε₂While other liquid crystals have epsilon₁<ε₂. Previous property ε₁Called positive dielectric anisotropy, the latter property ∈₂Referred to as negative dielectric anisotropy. Under an electric field,. epsilon₁And ε₂The larger the difference between them, the easier the orientation of the liquid crystal is controlled by the electric field. Liquid crystals with positive dielectric anisotropy are aligned parallel to the electric field, while liquid crystals with negative dielectric anisotropy are aligned vertically. Since the magnitude of the dielectric constant determines the responsivity and the mode of response, their control is one of the most important goals for the design of liquid crystal materials.

Selective reflection of light from cholesteric liquid crystals

Cholesteric liquid crystals or chiral nematic liquid crystals have a one-dimensional periodic structure based on the natural helical twisting power of these materials (see fig. 1). The natural twist is related to the molecular chirality of the liquid crystal molecules and/or dopants. The periodic structure produces bragg reflection of light when the pitch of the helical twist falls within the visible wavelength range. Unlike the simple bragg reflection of a multilayer interference filter, the reflection of cholesteric liquid crystals is more complicated by the continuously twisted structure of the optically anisotropic medium. One consequence of this fact is the selective reflection of circularly polarized light, and the other is the appearance of a clear selective reflection band with sharp band edges (see fig. 2A). The sharpness of the reflection band depends on the magnitude of the liquid crystal birefringence and the uniformity of the twist pitch. Furthermore, structural anomalies may make the band edges less sharp.

Since the periodic twisted structure is not perfect for the inherent flexibility of liquid crystals, there are many mechanisms that affect the reflection efficiency. Insertion loss is the reduction of light energy before and after reflection. Static defects scatter light; thermal fluctuations in molecular orientation are responsible for optical haze, wasting optical energy in the propagation process. A smaller spring constant results in larger structural thermal fluctuations and thus in larger insertion losses. Since flexibility is advantageous for higher sensitivity, there is always a trade-off between sensitivity, response speed and optical performance.

In one embodiment of the invention, the liquid crystal material consists of 2 to 25 components, such as 3 to 15 compounds, or 4 to 10 compounds, at least one of which is a chiral dopant derived from the bioavailable species described herein. The other compound may be a low molecular weight liquid crystalline compound selected from nematic or nematic substances. For example, the further compound may be selected from the known classes of azoxybenzenes, benzylideneanilines, biphenyls, terphenyls, phenyl or cyclohexyl benzoates, phenyl or cyclohexyl esters of cyclohexanecarboxylic acid, phenyl or cyclohexyl esters of cyclohexylbenzoic acid, phenyl or cyclohexyl esters of cyclohexylcyclohexanecarboxylic acid, cyclohexylphenyl esters of benzoic acid, cyclohexylphenyl esters of cyclohexanecarboxylic acid and cyclohexylphenyl esters of cyclohexylcyclohexanecarboxylic acid, phenylcyclohexanes, cyclohexylbiphenyls, phenylcyclohexylcyclohexanes, cyclohexylcyclohexanes, cyclohexylcyclohexenes, cyclohexylcyclohexylcyclohexylcyclohexenes, 1, 4-bis-cyclohexylbenzenes, 4' -bis-cyclohexylbiphenyls, phenylpyrimidines or cyclohexylpyrimidines, phenylpyridines or cyclohexylpyridines, phenylpyridazines or cyclohexylpyridazines, phenyldioxanes or cyclohexyldioxanes, phenyl-1, 3-dithiane or cyclohexyl-1, 3-dithiane, 1, 2-diphenylethane, 1, 2-dicyclohexylethane, 1-phenyl-2-cyclohexylethane, 1-cyclohexyl-2- (4-phenylcyclohexyl) ethane, 1-cyclohexyl-2-biphenylethane, 1-phenyl-2-cyclohexylphenylethane, optionally halogenated 1, 2-diphenylethylene, benzylphenyl ether, tolane, substituted cinnamic acids and other classes of nematic or nematic substances. The 1, 4-phenylene groups in these compounds may also be fluorinated.

LC characterization of pitch and helical twisting force

The helical cholesteric structure shown in fig. 2B is periodic in one dimension. Characterized by its pitch P, which is the distance along the helical axis with a rotation of the direction of the average molecular orientation through an angle of 360 °. The chiral dopant induces a helical structure; the pitch is inversely proportional to the concentration c of the chiral dopant. That is to say that the first and second electrodes,

where c is the concentration in weight fraction and P is the cholesteric pitch.

Experiment of

Glycyrrhetinic acid hexyl ester (1a)

In a 100ml recovery flask, 3 β -18 α glycyrrhetinic acid ("18 α β G") (0.470G, 1.0mmol), 1-iodohexane (0.232G, 1.1mmol), and anhydrous dimethylformamide (5ml) were placed. The mixture was stirred until homogeneous, then potassium carbonate (0.276g, 2.0mmol) was added. The mixture was stirred at room temperature overnight (although thin layer chromatography showed that the starting material was consumed within two hours). Ice water (20ml) was added dropwise with stirring, then 10% hydrochloric acid (5ml) was added, and then ice water was added to fill the flask. The solid was isolated by suction filtration, washed well with water and air dried. The compound was then absorbed into 15cc of silica gel with 50ml of ethyl acetate, the solvent was removed by rotary evaporation, and the absorbed material was then eluted on top of a short silica gel column (solvent: hexane/ethyl acetate 1: 1). The fractions containing pure product were concentrated to give a white solid which was recrystallized from isooctane (yield 0.348g, 63%). Melting point 98.2 ℃.1H-NMR (CDCl)₃,400MHz):δ＝0.78(s,6H,H-24,28),0.86(t,3H,CH3CH2-),1.00(s,3H,H-26),1.13(s,3H,H-23),1.14(s,3H,H-25),1.15(s,3H,H-29),1.27(s,3H,H-27),2.34(s,1H,H-9),2.79(ddd,1H,H-9),3.22(dd,H-3),4.10(m,2H,-CH2O-),5.65(s,1H,H-12).13C-NMR(CDCl₃,100MHz):δ＝14.1(C-6'),15.6(C-24),16.4(C-23),17.5(C-6),18.6(C-26),22.5(C-5'),23.4(C-27),25.6(C-3'),26.4(2C-16,15),27.3(C-2),28.1(C-25),28.4(C-28),28.5(C-29),28.7(C-2'),31.1(C-21),31.3(C-4'),31.8(C-17),32.7(C-7),37.0(C-10),37.7(C-22),39.1(2C-1,4),41.0(C-19),43.2(C-8),44.0(C-20),45.4(C-14),48.3(C-18),54.9(C-5),61.8(C-9),64.5(C-1'),78.7(C-3),128.5(C-12),169.3(C13),176.5(C-30),200.2(C-11)。

Glycyrrhetinic acid methyl ester (1b)

In a 100ml recovery flask, 18. alpha. beta.G (0.470G, 1.0mmol), methyl iodide (1.470G, 10.0mmol) and anhydrous dimethylformamide (5ml) were placed. The mixture was stirred until homogeneous, then potassium carbonate (0.276g, 2.0mmol) was added. The mixture was stirred at room temperature for two hours. Ice water (20ml) was added dropwise with stirring, then 10% hydrochloric acid (5ml) was added, and then ice water was added to fill the flask. The solid was isolated by suction filtration, washed well with water and air dried. Next, 50ml of ethyl acetate was added and the product was absorbed onto 15cc of silica gel. The absorbed material was placed on top of a silica gel column supplemented with hexane/ethyl acetate 3: 1. The eluent hexane/ethyl acetate 3:1 was used initially, with increasing polarity gradually to hexane/ethyl acetate 1: 1. The fractions containing the product were concentrated to give a solid which was recrystallized from isooctane/1-propanol (yield 0.468g, 97%). Melting point 242 ℃ and 245 ℃.1H-NMR (CDCl)₃,400MHz):δ＝5.66(s,1H,H-12),3.69(s,3H,-COOCH3),3.22(dd,1H,H-3),2.79(ddd,2H,H-1),2.34(s,1H,H-9),2.07(dd,1H,H-18),2.06-1.99(m,2H),1.98-1.80(m,4H),1.68-1.58(m,4H),1.45-1.39(m,3H),1.36(s,3H,H-27),1.32-1.20(m,4H),1.15(s,3H,H-28),1.13(s,3H,H-26),1.02(m,2H,H-15),0.99(s,3H,H-23),0.81(s,3H,H-24),0.81(s,3H,H29),0.69-0.72(m,2H)。

Oxidation of Glycyrrhetinic acid at the C3-hydroxy position to form 1C

In a 100ml recovery flask, 18 α β G (0.470G, 1.0mmol), tetrahydrofuran (5ml) and jones reagent (2.5M, 1ml) were placed. The mixture was stirred in an ice bath and after 1 hour thin layer chromatography indicated the consumption of all starting material. Ice water was added dropwise to fill the flask, and the solid was separated by suction filtration, washed with cold water and air-dried. The product was then taken up in 15cc of silica gel with 50ml of ethyl acetate. The absorbent was placed on top of a silica gel column and eluted with n-hexane/ethyl acetate 9:1 solvent (solvent: first n-hexane/ethyl acetate 9:1, increasing polarity gradually to 3:1 hexane/ethyl acetate). The fractions containing pure product were concentrated to give crystals which were recrystallized from isooctane (yield 0.441g, 94%). Melting point 293-. 1H-NMR (CDCl)₃,400MHz):δ＝5.75(s,1H,H-12),3.72-3.75(m,1H),2.95-2.98(m,1H),2.45(s,1H,H-9),1.38(s,3H,H-27),1.28(s,3H,H-29),1.23(s,3H,H-25),1.17(s,3H,H-26),1.11(s,3H,H-26),1.07(s,3H,H-24),0.86(s,3H,H-28)。

Methyl ester of 1c (1d)

In a 100ml recovery flask, 3,11-dioxo-olean-12-en-29-oic acid (3,11-dioxo-olean-12-en-29-oic acid) (0.1876g, 0.4mmol), anhydrous methanol (10ml) and 5 drops of concentrated H were placed₂SO₄. The mixture was refluxed for 48 hours, then thin layer chromatography indicated that all starting material had been consumed. 10ml of water are then added dropwise with stirring. The solid product was isolated by suction filtration, washed with water and air dried. It was then absorbed with 50cc of ethyl acetate on 15cc of silica gel and the absorbed material was placed on top of the silica gel column eluting with hexane/ethyl acetate 9:1 (solvent: first hexane/ethyl acetate 9:1, increasing polarity gradually to 3:1 hexane/ethyl acetate). The fractions containing pure product were concentrated to give a white solid which was recrystallized from isooctane/1-propanol (yield 0.066g, 34%). Melting point 245-. 1H-NMR (CDCl)₃,400MHz):δ＝5.71(s,1H,H-12),3.70(s,3H,-COOCH₃),2.98-2.94(m,1H),2.67-2.60(m,1H),2.44(s,1H,H9),1.37(s,3H,H-29),1.17(s,3H,H-25),1.15(s,3H,H-26),1.11(s,3H,H-23),1.07(s,3H,H-24),0.82(s,3H,H-28)。

Hexyl ester of 1c (1e)

In a 100ml recovery flask, 3,11-dioxo-olean-12-en-29-oic acid (0.188g, 0.4mmol), anhydrous dimethylformamide (5ml), potassium carbonate (0.111g, 0.8mmol) and 1-iodohexane (0.094g, 0.4mmol) were placed. The mixture was stirred for two hours, and then thin layer chromatography showed no starting material remaining. Then, 20ml of ice water was added dropwise, 10% hydrochloric acid was added to be slightly acidic, and ice-cold water was added dropwise to fill the flask. The solid compound was then isolated by suction filtration, washed with cold water and air dried. The dried compound was absorbed with 50cc of ethyl acetate on 15cc of silica gel, and the absorbed material was placed on top of the silica gel column and eluted with hexane/ethyl acetate 9:1 (solvent: first hexane/ethyl acetate 9:1, the polarity of the solvent was gradually increased to 3:1 hexane/ethyl acetate). The fractions containing pure product were concentrated to give a white solid which was recrystallized from isooctane (yield 0.153g, 69.8%). Melting point 144 ℃.1H-NMR (CDCl)₃,400MHz):δ＝5.69(s,1H,H-12),4.07-4.11(m,2H,-OCH3),2.99-2.94(m,1H),2.60-2.69(m,1H),2.44(s,1H,H-9),1.37(s,3H,H-27),1.27(s,3H,H-29),1.17(s,3H,H-25),1.15(s,3H,H-26),1.11(s,3H,H-23),1.07(s,3H,H-24),0.82(s,3H,H-28).13C-NMR(CDCl₃,100MHz):δ＝14.0(C-6'),15.7(C-25),18.5(C-26),18.8(C-6),21.4(C-5'),22.5(C-24),23.3(C-28),25.6(C-27),26.4(C-29),26.5(C-3'),28.4(C-16),28.6(C-15),28.7(C-2'),31.1(C21),31.4(C-4'),31.8(C-17),32.1(C-7),34.2(C-2),36.7(C-22),37.7(C-10),39.8(C-1),41.1(C-19),43.3(C-20),44.0(C-14),45.2(C-8),47.8(C-18),48.3(C-4),55.4(C-5),61.1(C-9),64.6(C-1'),128.4(C-12),169.8(C-13),176.5(C-30),199.4(C-11),217.2(C-3).

Methyl ester of 1b (1f)

In a 100ml recovery flask were placed 3-hydroxy-11-oxo-18-olean-12-en-30-oic acid methyl ester (0.155g, 0.32mmol), anhydrous tetrahydrofuran (10ml) and sodium hydride (15.36mg, 0.64 mmol). The mixture was stirred at room temperature for 30 minutes. Then, methyl iodide (0.136g, 0.96mmol, 3 equiv.) was added and stirred at room temperature for 5 hours. After 5 hours, thin layer chromatography indicated that no product was formed. Methyl iodide (0.094g, 0.64mmol)) was again added and the reaction mixture was refluxed for 30 hours. Thin layer chromatography indicated product formation and the mixture was allowed to cool to room temperature. Cold water (10ml) was added dropwise with stirring and the product was extracted with (10X 3) ml of dichloromethane. The organic phase was separated using a separatory funnel, then washed with water and dried over anhydrous magnesium sulfate. 15cc of silica gel was added and the solvent was evaporated. The absorbed material was placed on top of a silica gel column and the product was isolated with hexane/ethyl acetate 4:1 solvent (solvent: hexane/ethyl acetate 3: 1). The fractions containing pure product were concentrated to give a white solid, which was recrystallized from 1-PrOH (yield ═ 0.013g, 8.2%). Melting point 330-. 1H-NMR (CDCl)₃,400MHz):δ＝5.67(s,1H,H-12),3.69(s,3H,-OCH3),3.36(s,3H,CH3O-),2.82(ddd,1H,H-1),2.67(dd,1H,H-3),2.33(s,1H,H-9),1.30(m,1H,H-21),1.13(s,3H,H-25),1.13(s,3H,H-29),1.11(s,3H,H-26),0.97(s,3H,H-23),0.88(m,1H,H-10),0.79(s,3H,H-28),0.77(s,3H,H-24),0.67(m,1H,H-5)。

Acetyl ester of 1b (1g)

In a 100ml recovery flask, 3-hydroxy-11-oxo-18-olean-12-en-30-oic acid methyl ester (0.155g, 0.32mmol), anhydrous dichloromethane (5ml), acetyl chloride (50.24mg, 0.64mmol) and pyridine (1ml) were placed. The mixture was stirred under nitrogen atmosphere for 17 hours, after which it was thinLayer chromatography indicated that all reactants were consumed. Then 50ml of ice-cold water are added dropwise with stirring. The product was then extracted with dichloromethane (3X 20ml), washed with water and dried over magnesium sulphate. The solid obtained after evaporation of the solvent was then taken up with 50ml of ethyl acetate on 15cc of silica gel and the solvent was removed by rotary evaporation. The absorbed material was placed on top of a silica gel column and eluted with hexane/ethyl acetate 4:1 (solvent: first hexane/ethyl acetate 4:1, increasing the polarity of the solvent to hexane/ethyl acetate 3: 1). The fractions containing the pure compound were concentrated to give a white solid which was recrystallized from methanol (yield 0.082g, 49%). Melting point 292-. 1H-NMR (CDCl)₃,400MHz):δ＝5.67(s,1H,H-12),4.51(dd,1H,H-3),3.69(s,3H,-OCH3),2.80(ddd,1H,H-1),2.36(s,1H,H-9),2.08(m,1H,H-18),2.05(s,3H,-COOCH3),1.36(s,3H,H-27),1.16(s,3H,H-25),1.15(s,3H,H-29),1.13(s,3H,H-26),0.88(s,6H,H-23,24),0.81(s,3H,H-28),0.80(m,1H,H-5)。

Heptanoyl ester of 1a (1h)

In a 100ml recovery flask equipped with a stirring bar, 3-hydroxy-11-oxo-18-olean-12-en-30-oic acid hexyl ester (0.277g, 0.5mmol), anhydrous dichloromethane (5ml), heptanoyl chloride (0.082g, 0.55mmol) and pyridine (1ml) were placed. The mixture was stirred at room temperature overnight. Thin layer chromatography indicated that all reactants had been consumed and then 50ml of cold water was added dropwise with stirring. The product was extracted with dichloromethane (3X 20ml), washed with water, dried over magnesium sulfate and taken up on 15cc of silica gel with 50cc of ethyl acetate. The absorbed material was placed on top of silica gel eluting with hexane/ethyl acetate 9:1 (solvent: first hexane/ethyl acetate 9:1, increasing polarity gradually to 3: 1). Concentration of the fractions gave the solid product, which was recrystallized from methanol (yield 0.123g, 37%). Melting point 143.0-144.0 ℃.1H-NMR (CDCl)₃,400MHz):δ＝5.66(s,1H,H-12),4.51(dd,1H,H-3),4.9(t,2H,-OCH2-),2.80(ddd,1H,H-1),2.36(s,1H,H-9),2.30(t,2H,-OCOOCH3-),1.75-2.15(m,5H),1.57-1.75(m,10H),0.80-1.57(m,47H).13C-NMR(CDCl₃,100MHz):δ＝14.0,14.0,16.4,16.8,17.4,18.7,22.5,22.5,23.3,23.6,25.1,25.6,26.4,26.5,28.0 28.4,28.5,28.6,28.8,31.1,31.4,31.5,31.8,32.7,34.9,36.9,37.8,38.1,38.8,41.0,43.2,44.0,45.4,48.4,55.0,61.7,64.6,80.3,128.5,169.3,173.7,176.5,200.1。

Methyl ether (1i) of 3 beta-18 beta-glycyrrhetinic acid methyl ester

In a 100ml recovery flask with stirring bar, 3-hydroxy-11-oxo-18-olean-12-en-30-oic acid methyl ester (0.484g, 1.0mmol), anhydrous tetrahydrofuran (10ml) and potassium hydride (0.400g, 3.0mmol, 3 equiv, 30% dispersed in mineral oil) were placed. The mixture was cooled to 0 ℃ in an ice bath. Then, methyl iodide (0.426g, 3.0mmol, 3 equiv.) was added and the ice bath was removed. The mixture was stirred for one hour under an inert nitrogen atmosphere. Thereafter, the reaction was monitored by thin layer chromatography, indicating complete consumption of the reactants, yielding a less polar product. Concentrated hydrochloric acid (0.2ml) was added and the mixture was diluted with 50ml cold water. The precipitate obtained after addition of water was isolated by suction filtration, air-dried and taken up on 15cc of silica gel with 50ml of ethyl acetate. The absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1:9, solvent polarity gradually increased to 1: 3). The fractions were concentrated to give the solid product, which was recrystallized from 1-PrOH (yield 0.338g, 68%). Melting point 329.5-332.5 ℃.1H-NMR (CDCl)₃,400MHz):δ＝5.67(s,1H,H-12),3.69(s,3H,-OCH3),3.36(s,3H,CH3O-),2.84(ddd,1H,H-1),2.67(dd,1H,H-3),2.33(s,1H,H-9),1.36(s,3H),1.15(s,3H,H-25),1.14(s,3H,H-29),1.12(s,3H,H-26),0.99(s,3H,H-23),0.80(s,3H,H-28),0.79(s,3H,H24),0.67-0.79(m,1H,H-5)。

Benzyl ether (1i) of 3 beta-18 beta-glycyrrhetinic acid hexyl ester

With a stirring rodInto a 100ml recovery flask was placed the hydroxy ester (0.554g, 1.0mmol), anhydrous tetrahydrofuran (10ml), potassium hydride (0.226g, 2.0mmol, 30% dispersed in mineral oil, 2 equiv.) and benzyl bromide (0.342g, 2.0 mmol). The mixture was stirred at room temperature under an inert nitrogen atmosphere overnight. Thin layer chromatography indicated the formation of a new product and some unreacted starting material. Benzyl bromide (0.171g, 1.0mmol) and potassium hydride (0.113g, 1.0mmol, 30% dispersed in mineral oil) were then added again and stirred overnight. The reaction was again monitored by thin layer chromatography, but the same results were observed, i.e. two spots of starting material and product. The reaction was then made acidic by the addition of 10% hydrochloric acid (5.0ml) and quenched by the addition of 50ml cold water. The resulting precipitate was then isolated by suction filtration and taken up on 15cc of silica gel with 50ml of ethyl acetate. The absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:3 (solvent: ethyl acetate/hexane 1:3, solvent polarity gradually increased and reached 1: 1). The fractions were concentrated to give two solids (one product and one starting material). The product was recrystallized from isooctane to give 0.106g and 0.095g in two portions, for a total of 0.201g (yield: 31.2%). The amount of the raw material recovered was 0.233 g. Melting point 193 and 194 ℃.1H-NMR (CDCl)₃,400MHz):δ＝7.24-7.31(m,5H),5.65(s,1H),4.55(dd,1H),4.10(m,2H),2.94(dd,1H),2.85(ddd,1H),2.33(s,3H),1.16(s,3H),1.15(s,3H),1.13(s,3H),1.12(s,3H),0.86(s,3H),0.80(s,6H).13C-NMR(CDCl₃,100MHz):δ＝14.0,16.4,16.6,17.5,18.7,22.5,22.7,23.4,25.7,26.4,26.5,28.3,28.5,28.6,28.7,31.2,31.4,31.8,32.7,37.1,37.8,39.0,39.2,41.1,43.2,44.0,45.4,48.3,55.5,61.9,64.6,71.1,86.1,127.2,127.5(x2C),128.2(x2C),128.6,139.5,169.2,176.5,200。

Benzyl ether (1k) of 3 beta-18 beta-glycyrrhetinic acid methyl ester

Into a 100ml recovery flask equipped with a stirring bar were placed hydroxymethyl ester (0.484g, 1.0mmol), anhydrous tetrahydrofuran (10ml), potassium hydride (0.400g, 3.0mmol, 30% dispersed in mineral oil) and benzyl groupBromine (0.342g, 2.0 mmol). The mixture was stirred at room temperature under a nitrogen atmosphere overnight. Thin layer chromatography showed that all starting material had been consumed, resulting in a less polar product. Then 5ml of 10% hydrochloric acid were added and the mixture was diluted with 50ml of ice-cold water. The resulting precipitate was isolated by suction filtration and taken up on 15cc of silica gel with 50ml of ethyl acetate. The solvent was evaporated to dryness and the absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:3 (solvent: ethyl acetate/hexane 1: 3). The product containing fractions were concentrated to give a white solid which was recrystallized from toluene (yield 0.367g, 64%). Melting point 300-. 1H-NMR (CDCl)₃400MHz ═ 7.20-7.35(m,5H),5.67(s,1H, olefinic), 4.69(d,1H, benzyl), 4.41(d,1H, benzyl), 3.69(s,3H, -OCH3),2.93(dd,1H),2.83(dt,1H),1.85-2.09(m,6H),1.36(s,3H),1.15(s,3H),1.14(s,3H),1.12(s,3H),1.00(s,3H),0.87(s,3H),0.80(s, 3H).

Allylation of 1c '(18-beta isomer of 1 c) to prepare allyl ester (1 m')

Into a 100ml recovery flask with stirring bar was placed 3,11-dioxo-olean-12-en-29-oic acid (0.469gm, 1.0mmol), anhydrous dimethylformamide (10ml), potassium carbonate (0.276gm, 2.0mmol) and allyl bromide (0.334gm, 2.8 mmol). The mixture was stirred at room temperature under a nitrogen atmosphere for 30 minutes. Thin layer chromatography showed that all starting material had been consumed, resulting in a single less polar product. Then 50ml of ice-cold water are added dropwise with stirring and the mixture is made acidic by addition of 10% hydrochloric acid. The resulting precipitate was isolated by suction filtration, washed with water and air dried. The product was taken up in 50ml of ethyl acetate on 15cc of silica gel. The solvent was removed, and the absorbed material was placed on top of the column and eluted with ethyl acetate/hexane 1:3 (solvent: ethyl acetate/hexane 1: 3). The fractions were concentrated to give the solid product, which was recrystallized from isooctane (yield 0.365gm, 74%). Melting point: 150 ℃ and 152 ℃.1H-NMR (CDCl)₃,400MHz):δ＝0.82(s,3H),1.07(s,3H),1.11(s,3H),1.19(s,6H),1.27(s,3H),1.37(s,3H),2.33-2.39(m,1H),2.44(s,1H),2.60-2.67(m,1H),2.94-2.98(m,1H),4.58-4.66(m,2H,-OCH₂-),5.25(dd,1H, alkene H),5.34(dd,1H, alkene H),5.69(s,1H),5.87-5.97(m,1H, H)_2').13C-NMR(CDCl₃,100MHz):δ＝15.7,18.5,18.8,21.4,23.3,26.4(2xC),26.5,28.4,28.6,31.1,31.9,32.1,34.2,36.7,37.7,39.8,41.1,43.3,44.0,45.2,47.8,48.3,55.4,61.1,65.1,118.5,128.5,132.2,169.7,176.0,199.5,217.2

Trifluoroethyl ester of 1c (1n)

In a 100ml recovery flask with stirring bar, 3,11-dioxo-olean-12-en-29-oic acid (0.469gm, 1.0mmol), anhydrous dichloromethane (10ml), 2,2, 2-trifluoroethanol (0.110gm, 1.1mmol), N, N' -dicyclohexylcarbodiimide (0.226gm, 1.1mmol), 4-dimethylaminopyridine (1.2mg, 0.1mmol) were placed. The mixture was stirred at room temperature under a nitrogen atmosphere overnight. Thin layer chromatography showed two spots (one with less polar product and one with polar starting material). Additional 2,2, 2-trifluoropropanol (0.110gm, 1.1mmol), N' -dicyclohexylcarbodiimide (0.226gm, 1.1mmol), 4-dimethylaminopyridine (1.2mg, 0.1mmol) were added to ensure completion of the reaction. The mixture was stirred at room temperature overnight and 50ml of ice-cold water were added dropwise with stirring. No precipitate was observed even after the mixture was made acidic by addition of 10% HCl, so the product was extracted with ethyl acetate (25X 3ml), washed and MgSO₄And (5) drying. The product was then taken up on 15cc of silica gel with 50ml of ethyl acetate. The absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:3 (solvent: ethyl acetate/hexane 1: 3). The fractions were concentrated to give 0.180gm of starting material and solid product. The solid product was recrystallized from isooctane (yield 0.116gm, 21.1%). Melting point: 151 ℃ and 153 ℃.1H-NMR (CDCl)₃,400MHz):δ＝0.86(s,3H),1.07(s,3H,H-24),1.10(s,3H,H-23),1.16(s,3H,H-23),1.23(s,3H,H-25),1.28(s,3H,H-29),1.39(s,3H,H-27),2.45(s,1H,H-9),2.95-2.98(m,1H),4.41-4.51(m,2H,-CH₂CF₃),4.53-4.63(m,2H,-OCH₂-),5.69(s,1H,H-12).13C-NMR(CDCl₃,100MHz):δ＝15.7,18.5,18.8,21.4,23.4,26.4,26.5,28.1,28.5,29.7,31.0,31.8,32.1,34.2,36.7,37.5,39.8,40.9,43.3,44.3,45.2,47.8,48.2,55.4,59.9,60.2,61.1,128.6,169.0,174.8,199.4,217.2。

Isobutyl ester of 1c (1o)

In a 100ml recovery flask with stirring bar, 3,11-dioxo-olean-12-en-29-oic acid (0.430gm, 0.92mmol), anhydrous dimethylformamide (5ml), potassium carbonate (0.248gm, 1.8mmol) and 1-iodo-2-methylpropane (0.184gm, 1.0mmol) were placed. The mixture was stirred under nitrogen overnight. The reaction was monitored by thin layer chromatography, indicating that a new less polar product was formed and the starting material was completely consumed. Then, 20ml of ice water was added dropwise, the solution was made slightly acidic by adding 10% hydrochloric acid, and ice-cold water was added dropwise to fill the flask. The solid precipitate obtained is separated by suction filtration, washed with cold water and air-dried. The dried compound was absorbed onto 15cc of silica gel with 50cc of ethyl acetate, and the absorbed material was placed on top of the silica gel column, eluting with ethyl acetate/hexane 1:3 (solvent: ethyl acetate/hexane 1: 3). The fractions were concentrated to give the solid product, which was recrystallized from isooctane (yield 0.146gm, 30.3%). Melting point: 182 ℃ and 183 ℃.1H-NMR (CDCl)₃,400MHz):δ＝5.69(s,3H),3.89(dd,2H,-COOCH₂-),2.93-3.00(m,1H),2.59-2.68(m,1H),2.44(s,1H),1.38(s,3H),1.27(s,3H),1.17(s,3H),1.16(s,3H),1.11(s,3H),0.96(d,6H, two isobutyl CH' s₃),0.82(s,3H).13C-NMR(CDCl₃,100MHz):δ＝217.2,199.5,176.4,169.8,128.5,70.7,61.1,55.4,48.4,47.8,45.2,44.1,43.3,41.1,39.8,37.7,36.7,34.2,32.1,31.9,31.1,28.6,28.5,27.9,26.5,26.4(2xC),23.4,21.4,19.2,18.8,18.5,15.7。

1 isobutyl ester (1p)

In a 100ml recovery flask, 18. alpha. beta.G (0.400gm, 0.850mmol), 1-iodo-2-methylpropane (0.184gm, 1.0mmol) and anhydrous dimethylformamide (5ml) were placed. The mixture was stirred until homogeneous and potassium carbonate (0.138gm, 1.0mmol) was then added. The mixture was stirred at room temperature for 16 hours. After this time, thin layer chromatography indicated complete consumption of the starting material and the appearance of a single less polar product. Ice water (. about.20 ml) was added dropwise with stirring, then 10% hydrochloric acid (5ml) was added, and then ice-cold water was added to fill the flask. The solid was isolated by suction filtration, washed with water and air dried. The product was then taken up on 15cc of silica gel with 50ml of ethyl acetate. The solvent was removed by rotary evaporation and the absorbed material was placed on top of a short silica gel column and eluted with ethyl acetate/hexane 1:1 (solvent: ethyl acetate/hexane 1: 1). The fractions containing pure product were concentrated to give a white solid which was recrystallized from isooctane (yield 0.260gm, 49.4%). Melting point: 185 ℃ and 186 ℃.1H-NMR (CDCl)₃,400MHz):δ5.56(s,1H),3.89(ddd,2H,-COOCH₂-),3.21-3.27(m,1H),2.79(ddd,2H),2.34(s,1H),2.12(dd,1H),1.80-2.08(m,6H),1.58-1.68(m,6H),1.37(s,3H),1.16(s,3H),1.14(s,3H),1.13(s,3H),1.01(s,3H),0.96(d,6H, two CH' s₃),0.81(s,6H).13C-NMR(CDCl₃,100MHz):δ＝200.2,176.5,169.3,128.6,78.8,70.6,61.8,54.9,48.3,45.4,44.1,43.2,41.1,39.1,37.8,37.1,32.8,31.9,31.1,28.6,28.1,27.9,27.3,26.5,26.4(2xC),23.4,19.2(2xC),18.7,17.5,16.4,15.6。

Trifluoroethyl ester of 1(1 q)

A100 ml recovery flask equipped with a stirring bar was charged with glycyrrhetinic acid (0.940gm, 2.0mmol), anhydrous dichloromethane (10ml), 2,2, 2-trifluoroethanol (0.220gm, 2.2mmol), N' -dicyclohexylcarbodiimide (0.226gm, 1.1mmol), 4-dimethylaminopyridine (0.600mg, 2.9 mmol). The mixture was stirred at room temperature under a nitrogen atmosphere overnight. Thin layer chromatography showed complete consumption of starting material, resulting in a single less polar product. Adding dropwise ice-cold water under stirring. No precipitate was observed even after the mixture was made acidic by addition of 10% hydrochloric acid, so the product was extracted with ethyl acetate (25X 3ml), washed with brine and over MgSO₄And (5) drying. The product was then taken up on 15cc of silica gel with 50ml of ethyl acetate. The absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 (solvent: first ethyl acetate/hexane 1:9, solvent polarity gradually increasing to 1: 3). The fractions were concentrated to give two solids (one desired and one undesired). The desired product was removed from MeOH/H₂Recrystallization from O (yield 0.678gm, 61.4%). Melting point 160-. 1H-NMR (400MHz, CDCl)₃):δ＝0.69-0.71(m,1H),0.81(s,3H),1.01(s,3H),1.13(s,3H),1.14(s,3H),1.21(s,3H),1.33(s,3H),2.34(s,3H),2.75-2.84(m,1H),3.21-3.25(m,1H),4.44-4.57(m,2H),5.65(s,1H).13C-NMR(100MHz,CDCl₃):δ＝15.6,16.4,17.5,18.7,23.4,26.4(2xC),27.3,28.1(2xC),28.4,31.0,31.8,32.8,37.1,37.6,39.1,40.8,43.2,44.3,45.4,48.1,54.9,59.9,60.2,61.8,76.2,78.8,128.7,168.5,174.9,200.1.19F-NMR(376MHz,CDCl₃):δ＝-76.58(t,-CH₂CF₃)。

S-naringenin (2) derivatives

Trimethyl ester of S-naringenin (2a)

In a 100ml recovery flask, naringenin (0.272g, 1.0mmol), anhydrous dimethylformamide (5ml), potassium carbonate (0.690g, 5.0mmol) and methyl iodide (0.710g, 5.0mmol) were placed. The mixture was stirred at room temperature under a nitrogen atmosphere overnight. After this time, thin layer chromatography indicated that a small amount of product was formed, so additional amounts of methyl iodide (0.710g, 5.0mmol) and potassium carbonate (0.690g, 5.0mmol) were added. The reaction was again stirred overnight. After this time, thin layer chromatography showed that all reactants were consumed to obtain the product, since four new spots were observed on thin layer chromatography. Then 25ml of ice-cold water are added dropwise with stirring, and the mixture is rendered slightly acidic by the dropwise addition of 10% hydrochloric acid. The flask was filled by adding ice cold water. Will produceThe material was extracted with ethyl acetate (3X 50ml), washed with water and dried over anhydrous magnesium sulfate. The solid obtained after evaporation of the solvent was taken up with 50ml of ethyl acetate on 15cc of silica gel and the solvent was removed by rotary evaporation. The absorbed material was placed on top of a silica gel column and the product was isolated with hexane/ethyl acetate 4:1 (solvent: hexane/ethyl acetate 4:1, solvent polarity gradually increasing to 1: 1). Fractions were concentrated to give three different solids. The solid product obtained after concentration of fractions 13-17 gave a single spot on thin layer chromatography. The solids from fractions 18-23 also gave a single spot, while the solid product from fractions 24-28 gave two spots on thin layer chromatography. None of the fractions shared a common compound. Yield, product-1 (fractions 13-17) ═ 0.073g (dark brown waxy solid, melting at 70 ℃), product-2 (fractions 18-23) ═ 0.153g (brown solid, melting at 78 ℃), product-3 (fractions 24-28) ═ 0.010g (black solid, melting at 145 ℃). Data for suspect compound (product-2): 1H-NMR (CDCl)₃,400MHz):δ＝7.29-7.46(m,2H),6.82-6.90(m,2H),6.16(s,1H),3.86(s,3H),3.83(s,3H),3.76(s,3H),1.26-1.30(m,1H),0.80-0.90(m,1H)。

In a 100ml recovery flask, naringenin (0.544gm, 2.0mmol), anhydrous dimethylformamide (5ml), potassium carbonate (0.552gm, 4.0mmol) and methyl iodide (0.710gm, 5.0mmol) were added. The mixture was stirred at room temperature under a nitrogen atmosphere overnight. After this time, thin layer chromatography indicated that a small amount of product was formed, so additional amounts of methyl iodide (2.0mmol, 0.284gm) and potassium carbonate (0.138gm, 1.0mmol) were added. The reaction was stirred for six hours after which time thin layer chromatography showed four spots so methyl iodide (0.248gm, 2.0mmol) was added to complete the reaction. The reaction was allowed to proceed overnight. Thin layer chromatography was performed which showed complete consumption of starting material and formation of three new less polar products. Then, ice-cold water was added dropwise with stirring to fill the flask, and the mixture was made slightly acidic by adding 10% hydrochloric acid dropwise. No solid precipitate was seen, so the product was extracted with ethyl acetate (3X 50ml), washed with water and over anhydrous MgSO₄And (5) drying. The solid obtained after evaporation of the solvent was taken up with 50ml of ethyl acetate on 15cc of silica gel and the solvent was removed by rotary evaporation. Placing the absorbed substance in siliconAt the top of the gel column, the product was separated with hexane/ethyl acetate 3:1 (solvent: hexane/ethyl acetate 3:1, solvent polarity gradually increased to 1: 1). Fractions were concentrated to give three different pure solids.

Product-1 (trimethoxy naringenin)

Yield 0.144gm (yellow solid, recrystallized from isooctane). Melting point: 112 ℃ is carried out. 1H-NMR (CDCl)₃,400MHz):δ＝7.79(d,2H),7.56(d,2H),6.92(dd,2H),6.02(dd,2H),3.91(s,3H,-OCH₃),3.85(s,3H,-OCH₃),3.83(s,3H,-OCH₃).13C-NMR(CDCl₃,100MHz):δ＝192.6,168.4,166.0,162.5,161.4,142.5,130.1,128.3,125.1,114.4,106.4,93.8,91.2,55.8,55.6,55.4。

Product-2 (Dimethoxynaringenin)

Yield 0.090gm (white solid, recrystallized from isooctane). Melting point: 113 ℃ and 114 ℃.1H-NMR (CDCl)₃,400MHz):δ＝12.02(s,1H),7.38(d,2H),6.95(d,2H),6.05(dd,2H),5.37(dd,1H),3.83(s,3H,-OCH₃),3.81(s,3H,-OCH₃),3.06-3.14(m,1H),2.78(dd,1H).13C-NMR(CDCl₃100MHz) delta 196.0,167.9,163.7,164.1,162.9,160.1,130.4,127.7,114.2,95.1,94.2,79.0,55.7,55.3, 43.2. In agreement with literature NMR data for 7,4' -dimethoxynaringenin. (reference: Molecules,22,1485,2017)

Product-3 (Mono-methoxy naringenin)

Yield 0.055gm (pale yellow solid, recrystallized from isooctane). Melting point: 143 ℃ and 145 ℃.1H-NMR (CDCl)₃,400MHz):δ＝12.04(s,1H),7.37-7.29(m,2H),6.90-6.92(m,2H),6.07-6.10(m,2H),6.08(dd,2H),5.37(dd,1H),5.32(s,1H),3.83(s,3H,-OCH₃),3.08-3.15(m,1H),2.82-2.84(m,1H).13C-NMR(CDCl₃100MHz) delta 196.1,168.0,164.1,162.9,156.1,142.1,130.1,128.0,115.7,103.1,95.1,94.3,86.3,79.0,55.7, 43.2. In agreement with literature NMR data for 7-methoxynaringenin. Reference is made to the Molecules,22,1485,2017

In a 100ml recovery flask, naringenin (0.544gm, 2.0mmol), anhydrous dimethylformamide (5ml), potassium carbonate (0.552gm, 4.0mmol) and methyl iodide (0.710gm, 5.0mmol) were added. The mixture was stirred at room temperature under a nitrogen atmosphere overnight. After this time, thin layer chromatography indicated that a small amount of product was formed, so additional amounts of methyl iodide (2.0mmol, 0.284gm) and potassium carbonate (0.138gm, 1.0mmol) were added. The reaction was stirred for six hours after which time thin layer chromatography showed four spots, so methyl iodide (0.248gm, 2.0mmol) was added and the reaction allowed to proceed overnight. Then, ice-cold water was added dropwise with stirring to fill the flask, and the mixture was made slightly acidic by adding 10% hydrochloric acid dropwise. No solid precipitate was seen, so the product was extracted with ethyl acetate (3X 50ml), washed with water and over anhydrous MgSO₄And (5) drying. The solid obtained after evaporation of the solvent was taken up with 50ml of ethyl acetate on 15cc of silica gel and the solvent was removed by rotary evaporation. The absorbed material was placed on top of a silica gel column and the product was isolated with hexane/ethyl acetate 3:1 (solvent: hexane/ethyl acetate 3:1, solvent polarity gradually increased to 1: 1). The fractions were concentrated to give dimethoxynaringenin and monomethoxynaringenin as solid products, which were recrystallized from isooctane.

Dimethoxy naringenin

Yield 0.090gm (white solid, recrystallized from isooctane). Melting point: 113 ℃ and 114 ℃.1H-NMR (CDCl)₃,400MHz):δ＝12.02(s,1H),7.38(d,2H),6.95(d,2H),6.05(dd,2H),5.37(dd,1H),3.83(s,3H,-OCH₃),3.81(s,3H,-OCH₃),3.06-3.14(m,1H),2.78(dd,1H).13C-NMR(CDCl₃100MHz) delta 196.0,167.9,163.7,164.1,162.9,160.1,130.4,127.7,114.2,95.1,94.2,79.0,55.7,55.3, 43.2. In agreement with the literature NMR data for 7,4' -dimethoxynaringenin (ref: Molecules,22,1485,2017)

Monomethoxynaringenin:

yield 0.055gm (pale yellow solid, recrystallized from isooctane). Melting point: 143 ℃ and 145 ℃.1H-NMR (CDCl)₃,400MHz):δ＝12.04(s,1H),7.37-7.29(m,2H),6.90-6.92(m,2H),6.07-6.10(m,2H),6.08(dd,2H),5.37(dd,1H),5.32(s,1H),3.83(s,3H,-OCH₃),3.08-3.15(m,1H),2.82-2.84(m,1H).13C-NMR(CDCl₃100MHz) delta 196.1,168.0,164.1,162.9,156.1,142.1,130.1,128.0,115.7,103.1,95.1,94.3,86.3,79.0,55.7, 43.2. In agreement with literature NMR data for 7-methoxynaringenin. Reference is made to the Molecules,22,1485,2017

Triacetyl ester (2d) and 4', 7-diacetyl ester (2c) of S-naringenin

In a 100ml recovery flask equipped with a stirring bar, naringenin (0.272g, 1.0mmol), pyridine (5ml), acetic anhydride (5ml) and 4-dimethylaminopyridine (12.2mg, 0.1mmol) were placed. The mixture was stirred at room temperature overnight. Thin layer chromatography indicated that all starting material was consumed and two new products were observed on thin layer chromatography. Then 50ml of cold water are added dropwise with stirring, the product is extracted with diethyl ether (50X 3ml), washed with water, dried over magnesium sulfate and the solvent is evaporated. The solid product was taken up on 15cc of silica gel with 50ml of ethyl acetate. The absorbed material was placed on top of silica gel and the product was isolated with ethyl acetate/hexane 1:3 (solvent: ethyl acetate/hexane 1:3, solvent polarity gradually increasing to 1: 1). The fractions were concentrated to give two solids (triester and diester) which were recrystallized from methanol/water. Product-1 (triester): yield 0.010g, 2.5%. Data for product-1 (triester): melting point 151.5-156.5 ℃.1H-NMR (CDCl)₃400MHz) δ ═ 7.45(d,2H),7.15(d,2H),6.78(d,1H),6.54(d,1H),5.41(dd,1H),3.01-3.09(m,1H),2.82(dd,1H),2.39(s,3H),2.33(s,3H),2.30(s, 3H). Product-2 (diester): the yield was 0.148 g. Melting point 150-. Data for product-2 (diester): 1H-NMR (CDCl)₃,400MHz):δ＝12.01(s,1H),7.11-7.47(m,4H),6.19(d,2H),5.38(dd,1H),2.95(dd,1H),2.68(dd,1H),2.67(s,3H,-OAc),2.66(s,3H,-OAc).13C-NMR(CDCl3,100MHz):δ＝21.1,21.2,29.7,44.9,78.8,95.5,96.9.102.0,105.6,107.6,122.4,127.5,136.0,150.8,151.9,162.8,164.0,169.7,170.4,188.9。

Dibutyl ester of R-naringenin (2 ') (2' h)

In a 100ml recovery flask with a stirring bar and nitrogen inlet, naringenin (0.554g, 2.0mmol) and anhydrous tetrahydrofuran (10ml) were placed. The mixture was stirred in a cold water bath and butyric anhydride (0.95g, 6.0mmol) was added and the mixture was stirred for 15 minutes. Three portions of diisopropylethylamine (0.260 g each, 2.0mmol) were then added stepwise at 15 minute intervals to better assess the progress of the reaction. After 1 hour excess reagent was added: butyric anhydride (0.950g, 6.0mmol) and diisopropylethylamine (0.78g, 6.0 mmol). The resulting mixture was stirred at room temperature overnight, then water (. about.70 ml) was added dropwise with stirring. No solid product appeared even upon cooling, so the mixture was made acidic by adding hydrochloric acid dropwise, but this did not give any solid product. The mixture was transferred to a separatory funnel using ethyl acetate and water. The phases were separated and the organic phase was washed with water and transferred to a 500ml recovery flask. Add 25cc of silica gel and concentrate to dryness. The absorbed material was then placed on top of a silica gel column and eluted with dichloromethane/hexane 9:1 (solvent: dichloromethane/hexane 9: 1). The fractions were concentrated to give the solid product, which was identified as the bis-adduct (yield 0.390g, 41%). Data for the di-adduct: melting point 72.0-73.0 ℃.1H-NMR (DMSO-d6,400MHz): δ ═ 11.94(s,1H),7.57-7.60(m,2H),7.18-7.21(m,2H),6.36(dd,2H),5.74(dd,1H),3.42-3.50(m,1H),2.92(dd,1H),2.53-2.60(m,4H),1.59-1.71(m,4H),0.93-1.00(m, 6H): 13C-NMR (DMSO-d6,100MHz): δ ═ 198.2,172.1,171.2,162.7,162.5,158.5,151.1,136.2,128.5,122.5,106.3,103.3,102.2,78.7,42.7,35.7,18.3,18.2,13.8, 13.7.

Triacetyl ester (3a) of shikimic acid (3)

In a 250ml round bottom flask with a stir bar, shikimic acid (3.48g, 20.0mmol) and anhydrous pyridine (25ml) were placed. The mixture was stirred in a cold water bath and acetic anhydride (12.0g, 120.0mmol) was added portionwise over two minutes. The mixture was stirred overnight and thin layer chromatography indicated that no starting material was present and a new spot was present. The mixture was cooled in an ice-water bath and 10% hydrochloric acid (75ml) was added dropwise with stirring. The product fraction was clearly separated, so concentrated hydrochloric acid (15ml) was then added dropwise and the clear separation was significant. The mixture was transferred to a separatory funnel with the aid of ethyl acetate (150ml), and the phases were separated. The organic phase was washed with 5% hydrochloric acid and then with brine. The aqueous layer was extracted with ethyl acetate (50ml) and the combined organic extracts were dried over magnesium sulphate, filtered through a short pad of silica gel and concentrated to a viscous oil, which was kept under low vacuum (house vacuum). Yield 4.36g (72.6%). 1H-NMR (400MHz, CDCl3): δ ═ 2.08(3H, s)2.11(6H, d)2.49(H, dd)2.90(H, dd)5.31(H, dd)5.77(H, dd)5.79(H, dd)6.8(H, d).13CNMR (400MHz), CDCl3) δ 14.1,20.7,28.0,65.9,66.7,67.4,76.7,77.0,77.3,130.5,135.0,169.8,169.9.

Biphenyl ester of 3a (3b)

In a 250ml round bottom flask with stirring bar were placed (3R,4S,5R) -3,4, 5-tris (acetoxy) -1-cyclohexene-1-carboxylic acid (0.52g,2.0mmol), 4-phenylphenol (0.34g, 2.0mmol), 4-dimethylaminopyridine (4.0mg, 0.04mmol) and 10ml anhydrous tetrahydrofuran. The mixture was stirred until all compounds were dissolved, then N, N' -dicyclohexylcarbodiimide (0.45g, 2.0mmol) was added. Shortly after the addition of N, N' -dicyclohexylcarbodiimide, a precipitate appeared and after two hours the mixture was checked by thin layer chromatography for the presence of new product with a small amount of starting material. Additional anhydrous tetrahydrofuran and some silica gel were added to the mixture. The solvent was evaporated and the adsorbed material was kept under vacuum overnight. Separation was performed by silica gel column using 90% hexane and 10% ethyl acetate and elution was performed with a gradient up to 20% ethyl acetate. The product containing fractions were combined and concentrated to give a white (semi) solid as product. NMR was performed on the main product. Yield 0.6g (65%).1H-NMR(400MHz,CDCl₃):δ＝2.12(3H,s)2.14(6H,d)2.63(H,dd)3.04(H,dd)5.39(H,dd)5.85(H,dd)5.88(H,dd)7.04(H,d)7.23(2H,dd)7.46(2H,ddd)7.58(H,dd)7.62(4H,ddd).13C-NMR(400MHz,CDCl₃):δ＝20.7,21.0,28.4,66.1,66.7,67.4,76.6,77.0,77.3,121.6,127.1,127.4,128.2,128.8,130.7,134.6,139.2,140.2,149.9,164.0,169.8.IR:469.66,524.07,1196.08,1732.47.GC-Ms:451.24,429.12,327.15,281.17,207.25,170.11,152.14,121.15,111.15,73.19。

4' -Cyanobiphenyl ester of 3a (3c)

In a 250ml round bottom flask with stirring bar were placed (3R,4S,5R) -3,4, 5-tris (acetoxy) -1-cyclohexene-1-carboxylic acid (0.59g, 2.0mmol), 4-cyanobiphenyl (0.44g, 2.0mmol), DMAP (0.004g, 0.04mmol) and anhydrous THF (10 ml). The mixture was stirred until all material was dissolved, then DCC (0.515g, 2.5mmol) was added. A precipitate appeared shortly after the addition of DCC and after three hours the mixture was checked by TLC for the presence of new product and some starting material. The reaction was stopped by adding some silica gel and more THF to the mixture, despite the presence of starting material. The solvent was evaporated and the adsorbed material was kept under vacuum overnight. The fractions were separated through a silica gel column with 90% hexane and 10% ethyl acetate and eluted with a gradient up to 50% ethyl acetate. After evaporation of the solvent a white semi-solid product was obtained. Recrystallization from acetonitrile gave white crystals. Yield-0.39 g (39.8%). The product is: 4-Cyanobiphenyl (3R,4S,5R) -3,4, 5-tris (acetoxy) -1-cyclohexenoate. Melting point 59-61 ℃.¹HNMR(400MHz,CDCl₃)δ2.08(3H,s),2.12(6H,d,J＝3.9Hz),2.51(H,dd,J＝14.1,10Hz),3.10(H,dd,J＝10.1,3.9Hz),5.37(H,ddd,J＝10.1,10,3.9Hz),5.85(H,dd,J＝4.1,3.9Hz),5.95(H,dd,J＝4.1,3.9Hz),7.03(H,ddd,J＝8.9,1.5,0.5Hz),7.63(2H,ddd,J＝8.9,1.5,0.5Hz),7.69(2H,ddd,J＝8.7,1.5,0.5Hz),7.76(4H,ddd,J＝8.7,1.5,0.5Hz).¹³CNMR(400MHz),CDCl₃δ20.7,20.8,21.0,24.8,25.5,28.4,33.7,49.4,66.0,66.7,67.4,111.1,118.8,122.1,126.9,127.7,128.4,130.5,132.6,135.0,137.1,141.2,145.2,150.9,169.8,169.9 IR-1733.6,2226.5,2849.6,2927.7,3322.8 (expected Peak-ester-1735-1750, olefin-1600-1680, aromatic-1650-2000, nitrile-2200-2250, alkane-2850-2975). The expected mass of the desired product for GC-MS-478.9 is 477.

3a of 4-nitrophenyl ester (3d)

In a 250ml round bottom flask with stirring bar were placed (3R,4S,5R) -3,4, 5-tris (acetoxy) -1-cyclohexene-1-carboxylic acid (0.59g, 2.0mmol), 4-nitrophenol (0.27g, 2.0mmol), 4-dimethylaminopyridine (4.0mg, 0.04mmol) and 10ml anhydrous tetrahydrofuran. The mixture was stirred until all compounds were dissolved, then N, N' -dicyclohexylcarbodiimide (0.45g, 2.0mmol) was added. Precipitation occurred shortly after the addition of N, N' -dicyclohexylcarbodiimide and after two hours the mixture was checked by thin layer chromatography for the presence of new product and some starting material. More N, N' -dicyclohexylcarbodiimide (10%) was added to the mixture and stirred for two hours and checked by thin layer chromatography. When some starting material remained, the reaction was terminated. Additional anhydrous tetrahydrofuran and some silica gel were added to the mixture. The solvent was evaporated and the adsorbed material was kept under vacuum overnight. Separation was performed through a silica gel column using 90% hexane, 10% ethyl acetate and elution was performed with a gradient up to 50% ethyl acetate. The product was obtained as a white solid after evaporation of the product containing fractions. The yield was 0.94 g. 1H-NMR (400MHz, CDCl)₃):δ＝2.07(3H,s)2.14(6H,d)2.58(H,dd)3.04(H,dd)5.37(H,dd)5.85(H,dd)7.07(H,d)7.36(2H,dd)8.32(2H,dd).13C-NMR(400MHz),CDCl₃):δ＝20.76,66.02,66.61,76.7,77.01,77.33,122.38,125.34.IR:640.43,1038.57,1188.84,1736.27,2850.34,2928.13,3324.16.GC-Ms:421.0,355.17,327.23,281.17,267.1,207.18,191.24,73.11,56.08。

Acetonide of shikimic acid methyl ester (3e)

In a round-bottom flask, methyl shikimate (0.86g, 4.6mmol) was added to a solution of 2, 2-dimethoxypropane (12ml) and p-TsOH (24mg, 0.13 mmol). The reaction mixture was stirred at room temperature for 15 minutes. After 15 minutes, the mixture was checked on TLC plates. There are new products and some raw materials. Thus, the mixture was stirred for a further 15 minutes and checked by TLC. Starting material still appeared, so an additional 5% p-TsOH (1.2mg, 0.0065mmol) was added and stirring was continued for an additional 30 minutes. Some by-products are present thereafter, while some starting material is still present. By using saturated NaHCO₃The reaction was terminated by neutralization and extracted with ether. The organic phase is passed over MgSO₄Dried and concentrated to give the product as an oil. Separation was performed by silica gel column using 75% hexane and 25% ethyl acetate. The product was obtained as a colorless oil. Yield-0.53 g (53%). The product is: 3, 4-isopropylidene- (-) -shikimic acid methyl ester.¹HNMR(400MHz,CDCl₃)δ1.36(6H,s),2.56(1H,dd),2.65(1H,dd),3.83(3H,s),3.92(1H,dd),4.21(1H,ddd),5.1(1H,dd),6.71(1H,d)。¹³CNMR(400MHz,CDCl₃)δ25.7,27.1,29.3,52.1,68.6,72.2,77.8,109.7,130.5,134.0,166.62。

Diels-Alder product of S-alpha-phellandrene (4) (4a)

In a 500ml recovery flask with a stirring bar, maleic anhydride (4.90g, 50.0mmol) and ethyl acetate (20ml) were placed. The mixture was stirred until all dissolved, then α -phellandrene (7.92g, 86% purity, 50.0mmol) was added to give a yellow solution (charge transfer color). The mixture was stirred at room temperature overnight and the color disappeared. The mixture was boiled for two hours to ensure completion of the reaction. The mixture was cooled under stirring to give a white precipitate of crystalline product to which heptane (20ml) was added. The solid product was isolated by suction filtration, washed with some heptane and air dried. The product was isolated in two batches totaling 9.198g (79%).¹H-NMR(CDCl₃,400MHz):δ＝0.89(dd,6H, isopropyl), 1.045-1.131(m,2H),1.147-1.323(m,1H),1.766-1.829(m,4H),2.978-3.235(m,4H),5.787(d,1H, alkene H).

4a 4-iodoanilide (4b)

In a 100ml recovery flask, 4-iodoaniline (2.19g, 10.0mmol) and anhydrous tetrahydrofuran (10ml) were placed. The mixture was stirred and the anhydride (0.585g, 2.5mmol) was added stepwise every 15 minutes and a thin layer chromatography sample was taken 15 minutes after each addition. After the first addition, new more polar product was seen, but by the time the addition was complete, little reaction appeared to have occurred. The flask was fitted with a KR bulb as a condenser and the solution was boiled for 15 minutes. Thin layer chromatography showed little reaction progress. Acetic acid (20ml) was now added and the flask was equipped with a solvent stripper. The solution was heated and 15ml of volatile solvent was distilled off. Thin layer chromatography now shows the presence of a new product that is slightly less polar than 4-iodoaniline, and the absence of 4-iodoaniline and the originally formed intermediates. The reaction mixture was cooled and water was added dropwise with stirring to give a large amount of precipitate. The solid was collected by suction filtration, washed well with water and air dried. The material was recrystallized from 1-propanol and collected in two batches to a total of 4.096g (94%). Melting point 162.5-164.5 ℃.1H-NMR (CDCl)₃400MHz,. delta.0.89 (dd,6H, isopropyl), 1.07-1.16(m,2H),1.30-1.40(m,1H),1.58-1.61(m,1H),1.80-1.85(m,3H),2.90-3.01(m,2H),3.23-3.26(m,1H),3.60(t,1H),5.73(d,1H, alkene H),6.91-6.93(m,2H),7.75-7.75(m,2H), 13C-NMR (CDCl)₃,100MHz):δ＝20.5,20.6,21.1,25.9,30.7,33.2,35.7,38.2,43.6,45.1,45.9,93.7,122.0,128.2(2C),131.7,138.3(2C),141.7,177.6,177.9。

4a of 4-Ethylanilide (4c)

In a 100ml recovery flask, 4-ethylaniline (0.62g, 5.0mmol) and acetic acid (1)0 ml). Anhydride (1.17g, 5.0mmol) was added and the mixture was gradually heated to boiling in an oil bath. The mixture was boiled for 30 minutes and thin layer chromatography indicated the absence of 4-ethylaniline. The mixture was cooled to room temperature and water was added dropwise to fill the flask with stirring. The solid was isolated by suction filtration, washed well with water and then recrystallized from a mixture of methanol and water to give the product as white crystals (1.59g, 96%). Melting point 125.5 ℃.1H-NMR (CDCl)₃400MHz,. delta.0.88 (dd,2H, isopropyl), 1.07-1.11(m,2H),1.23(t,3H),1.32-1.39(m,1H),1.79-1.84(m,4H),2.65(q,2H),2.90-3.01(m,1H),3.23-3.26(m,1H),3.75(d,1H, alkene H),7.03-7.05(m,2H),7.25-7.27(m,2H), 13C-NMR (CDCl)₃,100MHz):δ＝15.4,20.5,20.7,21.1,28.6,30.8,33.3,35.7,38.2,43.6,45.1,45.9,122.0,126.3(2C),128.7(2C),129.5,141.6,144.8,178.2,178.5。

4a 2-biphenylimide (4d)

In a 100ml recovery flask, 2-aminobiphenyl (0.85g, 5.0mmol) and acetic acid (10ml) were placed. Anhydride (1.17g, 5.0mmol) was added and the mixture was gradually heated to boiling in an oil bath. The mixture was boiled for 90 minutes and thin layer chromatography indicated the absence of 2-aminobiphenyl. The mixture was cooled to room temperature and water was added dropwise to fill the flask with stirring. The solid was isolated by suction filtration, washed well with water and air dried (1.91g, 99%). At this point, the crude material obtained, which appeared to be a mixture of isomers by NMR before recrystallization (vinyl protons are the best indicator, appearing at δ 5.1 and δ 5.7, in a 1:4 ratio). Of this material, 1.8g was taken for recrystallization from methanol (1.034g, this material showed the same vinyl protons at δ 5.1 and δ 5.7, in a ratio of-2: 3. melting point 139.5-140.5 ℃.1H-NMR (CDCl)₃400 MHz. delta. 0.77-1.30(m),1.55-1.80(m),2.64-3.25(m),5.08(d, olefin H, isomer I),5.75(d, olefin H, isomer II),6.95-7.80(m),7.20-7.47(m), 13C-NMR (CDCl3, 100MHz. delta. 20.5,20.6,20.7,21.1,30.4,30.6,33.2,35.2,35.5,37.2,38.0,43.4,44.9,45.1,45.8,46.0,46.03,121.7,122.0,127.4,127.6,128.1,128.2,128.3,128.4,128.5,128.6,1287,128.9,129.2,129.6,130.1,130.7,131.8,138.6,140.9,141.2,141.7,141.9,178.1,178.5. Remarking: the signals from the 1H-NMR and 13C-NMR spectra were more abundant than expected, probably due to the presence of rotamers.

4a of 3, 5-dimethoxyanilide (4e)

In a 100ml recovery flask, 3, 5-dimethoxyaniline (0.77g, 5.0mmol) and acetic acid (10ml) were placed. The mixture was heated to 60 ℃ in an oil bath and the anhydride (1.17g, 5.0mmol) was added. The resulting mixture was refluxed for two hours, after which thin layer chromatography indicated that the reaction was complete. The mixture was cooled and water was added dropwise to give a viscous solid which could not be filtered. The mixture was then transferred to a separatory funnel with ethyl acetate and the phases were separated. The organic phase was washed with water and then transferred to a 1 liter round bottom flask, silica gel (25g) was added and the mixture was concentrated to dryness. The material was placed on top of a silica gel column, eluted with 5% ethyl acetate/95% hexane and a rapid gradient up to 20% ethyl acetate. The fractions containing pure product were combined and concentrated to a viscous oil, which solidified under vacuum overnight. This material was crystallized from methanol into large transparent diamonds. Yield 1.62g (88%). Melting point N/a. 1H-NMR (CDCl)₃400MHz,. delta.0.88 (dd,6H, isopropyl H),1.06-1.18(m,2H),1.33-1.39(m,1H),1.79-1.86(m,4H),2.89-3.00(m,3H),3.24-3.25(m,1H),3.77(s,6H, -OCH3 x 2),5.75(d,1H, alkene H),5.26-5.27(m,2H),6.46-6.47(m, 1H).

4' -pentyl-4-biphenylanilide (4f) synthesized from 4b

In a 500ml round bottom flask containing iodide precursor (1.09g, 2.5mmol) was placed 4-pentylphenylboronic acid (0.72g, 3.75mmol), dioxane (25ml) and water (10 ml). The flask was fitted with a condenser and nitrogen inlet, the mixture was stirred, potassium carbonate (1.03g, 7.5mmol) was added and the mixture was heated to 70 ℃ in an oil bath while degassing with nitrogen. Adding catalyst PdCl₂(PPh₃)₂(35mg, 2%) and the reaction was held at 95 ℃ for three hours. From the thin layer chromatography, it is not clear whether the reaction is completed (the starting material and the product cannot be clearly distinguished), but all palladium has precipitated as a metal, thus terminating the reaction. The mixture was cooled and water (125ml) was added with stirring. The crystalline compound was precipitated and collected by suction filtration, washed well with water and air dried (crude yield ═ 1.330 g). The crude product was checked by 1H-NMR and looked like the correct product, so it was taken up on 15cc silica gel and placed on top of a silica gel column, eluting with 20% ethyl acetate/80% hexane (solvent: ethyl acetate/hexane 1:4, solvent polarity gradually increasing to 1: 3). The fractions were concentrated to give two solid products, which were recrystallized from methanol (yield ═ 0.949g, 83.5%). Melting point 195.0-196.0 ℃.1H-NMR (CDCl)₃400 MHz. delta. 0.88(dd,6H, isopropyl), 0.90-0.94(m,3H),1.17-1.20(m,2H),1.33-1.37(m,5H),1.55-1.67(m,2H),1.81-1.88(m,4H),2.64(q,2H),2.90-3.02(m,3H),3.26-3.28(m,1H),5.75(d,1H),7.19-7.26(m,4H),7.55(m,4H), 13C-NMR (CDCl)₃,100MHz):δ＝14.1,20.5,20.7,21.1,22.6,30.8,31.2,31.6,33.3,35.6,35.7,38.2,43.7,45.2,46.0,122.0,126.7(2C),126.1(2C),127.8(2C),128.9(2C),130.8,137.6,141.6,141.7,142.6,178.1,178.4。

4a 1-naphthalimide (4g)

In a 100ml recovery flask with a stirring bar, 1-naphthylamine (0.712g, 5.0mmol) and acetic acid (10ml) were placed. The mixture was homogenized by stirring at room temperature, then the anhydride (1.170g, 5.0mmol) was added. After two hours, thin layer chromatography showed no product formationThus, the mixture was refluxed overnight. The reaction was monitored by thin layer chromatography, which indicated that all reactants were consumed to give the product. The work-up consists in adding 50ml of cold water dropwise with stirring and separating the solid product by suction filtration. The product was then absorbed on 20cc of silica gel with 50ml of ethyl acetate. The absorbed material was placed on top of silica gel and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1:9, solvent polarity gradually increased to 1: 1). The fractions were concentrated to give the solid product. Thin layer chromatography of the product showed two spots indicating the presence of rotamers. Separately, 0.224g of crude product was retained and the remainder recrystallized from methanol/water. Finally, the product was divided into two batches (crude 0.224g and recrystallisation 1.336g) for a total of 1.560g (yield 87%). Melting point 144.8-145.8 ℃.1H-NMR (recrystallized product, isomer mixture) (CDCl)₃400 MHz. delta. 0.89(dd),1.13-1.22(m),1.42-1.56(m),1.86-1.93(m),3.09-3.11(m),3.36(dd),5.85(d),6.03(d),7.05-7.26(m),7.56-7.46(m),7.87-7.92(m), 13C-NMR (recrystallized product, isomer mixture) (CDCl)₃100MHz): δ ═ 20.8,21.1,21.2,30.7,30.8,33.2,33.3,35.5,35.8,38.0,38.3,43.8,44.6,45.2,45.5,46.2,46.4,122.1,122.2,122.3,123.1,125.4,125.9,126.2,126.4,126.5,126.8,127.0,128.5,128.6,129.0,129.2,129.4,129.6,129.8,129.9,134.4,141.8,142.5,178.4,178.6,178.7. Remarking: the signals of the 1H-NMR and 13C-NMR spectra are more abundant than expected, probably due to the presence of two rotamers.

Diacetyl ester (5a) of betulin (5)

In a 100ml recovery flask with a stirring bar, betulin (0.443g, 1.0mmol), anhydrous pyridine (10ml), acetic anhydride (0.306g, 3.0mmol) and 4-dimethylaminopyridine (12.2mg) were placed. The mixture was stirred at room temperature under a nitrogen atmosphere overnight. Thin layer chromatography indicated that all reactants were consumed, resulting in a less polar product. Then 25ml of water and 25ml of dichloromethane are added dropwise with stirring. The mixture was made acidic by addition of 10% hydrochloric acid and the organic phase was acidified with dichloromethaneAlkane (3X 25ml) was extracted, washed and dried over magnesium sulfate. The product was then absorbed on 15cc of silica gel, and the absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 solvent (solvent: ethyl acetate/hexane 1:9, the polarity of the solvent gradually increased to 1: 3). The product containing fractions were concentrated to give a white solid which was recrystallized from methanol (yield 0.349g, 61%). Melting point 220 ℃ and 221 ℃.1H-NMR (400MHz, CDCl)₃):δ＝0.83(s,3H),0.84(s,3H),0.97(s,3H),1.03(s,3H),1.39(s,3H),1.68(s,3H),2.04(s,3H),2.07(s,3H),2.40-2.49(m,1H),3.84(d,1H),4.24(d,1H),4.46(dd,1H),4.59(s,1H),4.69(s,1H)。

Diheptyl ester of betulin (5) (5b) and betulin-28-heptanoate (5c)

In a 100ml recovery flask with a stirring bar, betulin (0.443g, 1.0mmol), anhydrous dichloromethane (10ml), heptanoyl chloride (0.327g, 2.2mmol) and pyridine (1ml) were placed. The mixture was kept under nitrogen and stirred at room temperature overnight. After 3 hours, additional heptanoyl chloride (0.149g, 1.0mmol) was added to ensure complete reaction and the mixture was stirred overnight. Thin layer chromatography showed the formation of two compounds, one with weak polarity and one with lower polarity. Then 50ml of cold water was added dropwise with stirring, but no solid precipitate was observed, so the product was extracted with dichloromethane (3 × 25ml), washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated and the resulting liquid was taken up in 50cc of ethyl acetate on 15cc of silica gel. The absorbed material was placed on top of silica gel and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1:9, solvent polarity gradually increased to 1: 3). The fractions containing each pure product were concentrated to give two different colorless viscous liquids. They are identified as monoesters and diesters. Data for monoesters: yield 0.300g, 45%. 1H-NMR (CDCl)₃,400MHz):δ＝4.68(d,1H),4.58-4.61(m,1H),4.44-4.49(m,1H),4.25(d,1H),3.83(d,1H),2.40-2.50(m,1H),2.27-2.34(m,3H),1.90-2.00(m,1H),1.41-2.34(m,15H),1.10-1.41(m,17H),1.06-1.15(m,2H)1.01(s,3H),0.90(s,),0.83-0.89(m,12H),0.77-0.79(m,1H).13C-NMR(CDCl₃100MHz): δ ═ 14.0,14.7,16.0,16.2,16.6,18.2,19.1,20.8,22.5,23.7,25.0,25.1,27.0,27.9,28.9,29.6,29.7,31.4,34.1,34.5,34.6,34.9,37.1,37.5,37.8,38.4,40.8,42.7,46.4,47.7,48.8,50.3,55.4,62.5,109.9,150.2,173.7,174.4. data for diesters: yield 0.343g, 51%. 1H-NMR (CDCl)₃,400MHz):δ＝4.68(d,1H),4.58-4.59(m,1H),4.25(d,1H),3.83(d,1H),3.16-3.21(m,1H),2.40-2.50(m,1H),2.30-2.37(m,4H),1.45-2.01(m,17H),1.15-1.43(m,23H),1.04-1.14(m,2H),1.02(s,3H),0.90-1.00(m,5H),0.84-0.93(m,8H),0.82(s,3H),0.67-0.69(m,1H).13C-NMR(CDCl₃,100MHz):δ＝14.0(2xC),14.8,15.4,16.0,16.1,18.3,19.1,20.8,22.5,22.5,24.7,25.0,25.2,27.0,27.3,28.0,28.7,28.8,29.6,29.8,31.4,31.5,33.9,34.2,34.5,34.6,37.1,37.6,38.7,38.8,40.9,42.7,46.4,47.7,48.8,50.4,55.3,62.5,79.0,109.8,150.2,174.4,179.2。

Dibutylenyl ester of betulin (5) (5d) and betulin-28-butanoate (5e)

Into a 100ml recovery flask equipped with a stirring bar were placed betulin (0.443g, 1.0mmol), pyridine (10ml), butyric anhydride (0.475g, 3.0mmol) and 4-dimethylaminopyridine (12.2 mg). The mixture was stirred at room temperature under nitrogen overnight (although the reaction was completely consumed after 1 hour). Thin layer chromatography showed the formation of two new compounds (one with slight polarity and the other with lower polarity). Then 50ml of ice-cold water are added dropwise with stirring. No precipitate was observed even after the solution was made acidic by addition of 10% hydrochloric acid, so the product was extracted with dichloromethane (25 × 3ml), washed with water and dried over anhydrous magnesium sulfate. The product was then absorbed on 15cc of silica gel and the solvent was evaporated to dryness. The absorbed material was then placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1:9, solvent polarity gradually increasing to 1: 3). The fractions containing each pure product were concentrated to give two colorless solids, which were identified as single additionsA compound and a di-adduct. Data for mono-adduct (recrystallized from isooctane): yield 0.029g, 5%. Melting point 149.5-150.5 ℃.1H-NMR (CDCl)₃,400MHz):δ＝4.68(d,1H),4.58-4.60(m,1H),4.45-4.50(m,1H),4.26(dd,1H),3.84(d,1H),2.41-2.49(m,1H),2.27-2.33(m,3H),1.90-2.00(m,1H),1.71-1.86(m,2H),1.59-1.70(m,9H),1.56(s,3H),1.48-1.53(m,1H),1.35-1.44(m,4H),1.15-1.32(m,5H),1.04-1.13(m,2H),1.03(s,3H),0.93-0.97(m,7H),0.83-0.89(m,9H),0.77-0.81(m,1H).13C-NMR(CDCl₃100MHz): δ — 13.7,14.7,15.4,16.0,16.1,18.2,18.5,19.1,20.8,25.2,27.0,27.4,27.9,29.6,29.8,34.1,34.6,36.4,37.2,37.6,38.7,38.9,40.9,42.7,46.4,47.7,48.8,55.3,62.5,79.0,109.8,150.2,174.2. Data for the di-adduct (recrystallization from methanol): yield 0.362g, 62%. Melting point 102-. 1H-NMR (CDCl)₃,400MHz):δ＝4.68(d,1H),4.58-4.59(m,1H),4.26(dd,1H),3.85(d,1H),3.16-3.20(m,1H),2.41-2.49(m,1H),2.31(t,2H),1.91-2.05(m,1H),1.50-1.87(m,16H),1.34-1.45(m,5H),1.15-1.33(m,8H),1.05-1.15(m,1H),1.03(s,3H),0.93-0.99(m,8H),0.85-0.89(m,5H),0.82(s,3H),0.76(s,3H),0.76(s,3H),0.67-0.69(m,1H).13C-NMR(CDCl₃,100MHz):δ＝13.7,14.7,16.0,16.1,16.6,18.1,18.5,18.6,19.1,20.8,23.7,25.2,27.0,28.0,29.6,29.8,34.1,34.6,36.4,36.7,37.1,37.6,37.8,38.4,40.9,42.7,46.4,47.7,48.8,50.3,55.4,62.5,80.6,109.8,150.2,173.4,174.2。

Di-p-toluoyl ester (5f) of betulin (5)

In a 100ml recovery flask with a stirring bar, betulin (0.443g, 1.0mmol), p-toluic acid (0.286g, 2.1mmol), N' -dicyclohexylcarbodiimide (0.433g, 2.1mmol), 4-dimethylaminopyridine (0.122g, 1.0mmol) and anhydrous dichloromethane (20ml) were placed. The mixture was stirred at room temperature under a nitrogen atmosphere for 5 hours. Thin layer chromatography indicated that all reactants were consumed, yielding a single product. Then, 50ml of ice-cold water was added dropwise with stirring. Even after the mixture was made acidic by addition of 10% hydrochloric acid, it was not observedTo product, the product was extracted with dichloromethane (25 × 3ml), washed and dried over magnesium sulfate. The product was then taken up on 15cc of silica gel with 50ml of ethyl acetate. The absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:3 (solvent: ethyl acetate/hexane 1: 3). The fractions were concentrated to give the solid product, which was recrystallized from 1-PrOH (yield ═ 0.089g, 13%). Melting point 207-. 1H-NMR (CDCl)₃,400MHz):δ＝7.91-7.95(m,4H),7.22-7.25(m,4H),4.68-4.73(m,2H),4.61-4.62(m,1H),4.51(d,1H),4.07(d,1H),2.49-2.57(m,1H),2.39-2.43(m,6H),1.72(s,3H),1.57(s,6H),1.06(s,3H),1.02(s,3H),0.99(s,3H),0.91(s,3H).13C-NMR(CDCl₃,100MHz):δ＝14.1,14.8,16.1,16.2,16.8(x2C),18.2,19.2,20.9,21.6,21.7,22.7,23.8,25.2,27.2,28.1,29.7,30.0,34.1,34.7,37.1,37.7,38.2,38.4,40.9,42.8,46.7,47.8,48.9,50.3,55.5,63.1,81.3,109.9,127.8,128.3,129.0,129.1,129.5,129.6(x2C),143.3,143.5,150.2,166.4,167.1。

Dimethyl ether of betulin (5g)

Into a 100ml recovery flask with a stir bar were placed betulin (0.442g, 1.0mmol), 10ml anhydrous tetrahydrofuran, potassium hydride (0.553g, 4.0mmol, 30% dispersed in mineral oil), and methyl iodide (0.568g, 4.0 mmol). The mixture was stirred at room temperature overnight under a nitrogen atmosphere (although thin layer chromatography showed that all starting material was consumed in 1 hour to give a single product). The mixture was then made acidic by the addition of 5.5ml of 10% hydrochloric acid and diluted by the addition of 50ml of ice cold water. The solid precipitate obtained is isolated by suction filtration and taken up on 15cc of silica gel with 50ml of ethyl acetate. The solvent was evaporated to dryness and the absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1: 9). The product containing fractions were concentrated to give a white solid which was recrystallized from acetonitrile (yield 0.429g, 91%). Melting point 177-. 1H-NMR (CDCl)₃,400MHz):δ＝1.68(s,3H),2.63(mt,1H)；3.04(d,1H),3.48(d,1H),3.35(s,6H,2x OCH3),4.58(m,1H),4.68(m,1H)。

Benzyl ether of betulin (5h)

In a 100ml recovery flask with stirring bar, betulin (0.442g, 1.0mmol), anhydrous tetrahydrofuran (10ml), potassium hydride (0.553g, 4.0mmol, 30% dispersed in mineral oil) and benzyl bromide (0.513g, 3.0mmol) were placed. The mixture was stirred at room temperature overnight (although all starting material was consumed as shown by thin layer chromatography to give a single product). Then 2ml of 10% hydrochloric acid was added dropwise and ice-cold water was added to fill the flask. The resulting precipitate was isolated by suction filtration, air dried and taken up on 15cc of silica gel with 50cc of ethyl acetate. The solvent was evaporated, and the absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1: 9). The fractions were concentrated to give the solid product, which was recrystallized from acetonitrile (yield ═ 0.596g, 96%). Melting point 141-. 1H-NMR (CDCl)₃,400MHz):δ＝7.25(m,10H),4.40-4.46(m,6H),3.50(d,1H),3.09(d,1H),2.88(dd,1H),2.32-2.39(m,1H),1.67(s,3H),1.55(s,3H),1.26(s,3H),0.97(s,3H),0.93(s,3H),0.83(s,3H),0.81(s,3H).13C-NMR(CDCl₃,100MHz):δ＝14.1,14.8,15.8,16.1,16.4,18.3,19.1,20.8,22.7,22.9,25.2,27.1,28.2,29.4,29.9,30.0,30.1,31.9,34.2,34.9,37.1,37.4,38.6,39.0,40.9,42.6,47.3,47.9,48.8,50.4,55.8,68.0,71.3,73.4,86.5,109.5,127.2,127.5,127.6,128.2,128.3,139.0,139.5,150.8。

5 diallyl ether (5i)

Into a 100ml recovery flask with a stirring bar were placed betulin (0.442g, 1.0mmol), anhydrous THF (15ml), potassium hydride (0.400g, 3.0mmol, 30% dispersed in mineral oil). The mixture was stirred at room temperature under a nitrogen atmosphere overnight. After this time, thin layer chromatography indicated that all starting material was consumed, yieldingA single less polar product. For the post-treatment, 2ml of 10% hydrochloric acid and ice-cold water were added dropwise to fill the flask. The resulting precipitate was isolated by suction filtration, air dried and taken up on 15cc of silica gel with 50cc of ethyl acetate. The solvent was removed and the absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1: 9). The fractions were concentrated to give the solid product, which was recrystallized from acetonitrile (yield 0.510g, 98%). Melting point: 125 ℃ and 127 ℃.1H-NMR (CDCl)₃,400MHz):δ＝5.88-5.97(m,2H),5.11-5.30(m,4H),4.62(dd,2H,H29),3.85-4.15(m,4H,2x–OCH₂-),3.53(d,1H,H28),3.08(d,1H,H28),2.79(dd,1H,H3),2.40(ddd,1H,H19),1.68(s,3H),1.01(s,3H),0.96(s,3H),0.95(s,3H),0.83(s,3H),0.78(s,3H).13C-NMR(CDCl₃,100MHz):δ＝14.8,16.0,16.1,16.3,18.3,19.11,20.9,23.1,25.2,27.2,28.1,29.7,30.0,34.2,34.8,37.1,37.5,38.6,38.9,41.0,42.6,47.2,48.0,48.9,50.4,55.8,68.1,70.7,72.5,86.3,109.5,115.9,116.7,135.4,135.9,150.8。

Bistrifluoroacetyl esters (5j) of betulin (5)

In a 100ml recovery flask with a stirring bar, betulin (0.443g, 1.0mmol), anhydrous pyridine (10ml), trifluoroacetic anhydride (0.105g, 5.0mmol) and 4-dimethylaminopyridine (0.366g, 3.0mmol) were placed. The mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. Thin layer chromatography showed that all reactants were consumed, resulting in a less polar product. The mixture is diluted with 20ml of ethyl acetate and 15ml of 10% hydrochloric acid are added dropwise with stirring. Then ice-cold water was added dropwise with stirring to fill the flask. No precipitate was observed, so the organic phase was extracted with ethyl acetate (50X 2ml), washed with brine and anhydrous MgSO₄And (5) drying. The product was then taken up on 15cc of silica gel with 50ml of ethyl acetate. The solvent was removed, and the absorbed material was placed on top of a silica gel column and eluted with an ethyl acetate/hexane 1:9 solvent (solvent: ethyl acetate/hexane 1: 9). Concentrating the fractions to obtain a solid product, which is separated from isooctaneCrystal (yield 0.162gm, 26%). Melting point 208-.¹H NMR(400MHz,CDCl₃):δ＝4.60-2.72(m,3H),4.57(d,1H),4.13(d,1H),2.40-2.47(m,1H),1.69(s,3H),1.05(s,3H),0.99(s,3H),0.90(s,3H),0.89(s,3H),0.88(s,3H).¹⁹F NMR(376MHz,CDCl₃) Delta-75.28 and-74.86 (s, 2xCF respectively)₃)。

5 Dipentanoyl ester (5k)

Into a 100ml recovery flask with a stir bar were placed betulin (0.443g, 1.0mmol), anhydrous pyridine (10ml), valeric anhydride (0.306g, 5.0mmol), and 4-dimethylaminopyridine (0.366gm, 3.0 mmol). The mixture was stirred at room temperature under a nitrogen atmosphere overnight. Thin layer chromatography indicated complete consumption of starting material and formation of a less mono-polar product. The mixture was diluted with 25ml of ethyl acetate and made acidic by addition of 10ml of 10% hydrochloric acid. The flask was then filled with ice cold water. No precipitate was observed, so the organic phase was extracted with ethyl acetate (2X 50ml), washed with brine and over MgSO₄And (5) drying. The product was then taken up on 15cc of silica gel with 50ml of ethyl acetate. The solvent was removed by rotary evaporation and the absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1: 9). The fractions were concentrated to give a semi-solid product which did not crystallize upon standing for a long time (yield 0.583gm, 96%). 1H-NMR (400MHz, CDCl)₃):δ＝0.67-0.69(m,1H),0.84(s,6H),0.85(s,3H),0.97(s,3H),0.85-0.95(m,7H),1.03(s,3H),1.91-2.05(m,1H),2.28-2.35(m,4H),2.41-2.49(m,1H),3.85(d,1H),4.26(dd,1H),4.41-4.49(m,1H),4.48-4.59(m,1H),4.68(d,1H).13C-NMR(100MHz,CDCl₃):δ＝13.8,14.7,16.0,16.2,16.6,18.2,19.1,20.8,22.3(2xC),23.7,25.1,27.0,27.1,27.3,28.0,29.6,29.8,34.1,34.3,34.6(2xC),37.1,37.6,37.8,38.4,40.9,42.7,46.4,47.7,48.8,50.3,55.4,62.5,75.0,80.6,109.9,150.2,173.7,174.4。

Dihydrobetulin (5m)

Into a 200ml recovery flask with a stirring bar were placed betulin (4.420g, 10.0mmol), ethanol (40ml), anhydrous dichloromethane (40ml) and 10% palladium on carbon (0.442 g). The flask was evacuated and refilled with hydrogen from a hydrogen balloon attached to the flask via an adapter. The evacuation and refilling process was repeated 3 times, and then the mixture was stirred at room temperature under a hydrogen atmosphere overnight. The mixture was then diluted with 50ml ethyl acetate and filtered through a pad of celite. The filter cake was washed with ethyl acetate, the solvent was removed and the resulting solid was triturated with water. The product was isolated by suction filtration and air dried. 1H-NMR showed the product formed in pure form (yield 2.490gm, 56%). Melting point 269-271 ℃.1H-NMR (400MHz, CDCl)₃):δ＝0.76(s,3H),0.77(s,3H),0.77(s,3H),0.83(s,3H),0.85(s,3H),0.96(s,3H),0.97(s,3H),1.03(s,3H),3.20(dd,1H),3.30(d,1H),3.77(d,1H)。

5m diacetyl ester (5n)

Into a 100ml recovery flask with a stir bar, dihydrobetulin (0.444gm, 1.0mmol), pyridine (10ml), 4-dimethylaminopyridine (0.061g, 0.5mmol) and acetic anhydride (0.306g, 3.0mmol) were placed. The mixture was stirred at room temperature under a nitrogen atmosphere overnight. Thereafter, thin layer chromatography indicated complete consumption of the starting material and formation of a less mono-polar product. Then, 50ml of ice-cold water was added dropwise with stirring. The resulting precipitate was isolated by suction filtration, washed with water and air dried. The crude product obtained is then taken up on 15cc of silica with 50ml of ethyl acetate and evaporated to dryness. The absorbed material was placed on top of a silica gel column and eluted with hexane/ethyl acetate 4:1 (solvent: hexane/ethyl acetate 4: 1). The fractions containing the product were concentrated to give a solid which was recrystallized from isooctane (yield 0.404g, 77%). Melting point 251-. 1H-NMR (400MHz, CDCl)₃):δ＝4.46(dd,1H),4.24(d,1H),3.82(d,1H),2.08(s,3H,CH₃CO-),2.04(s,3H,CH₃CO-),1.03(s,3H),0.95(s,3H),0.85(s,3H),0.84(s,3H),0.83(s,3H),0.77(d,6H)。

Preparation of racemic 1 '-phenethyl-malimide (1' -phenylethyl-malimide) (6a) from D (+) -malic acid (6)

In a 100ml recovery flask with a stir bar, D- (+) -malic acid (1.056g, 8.0mmol), xylene (20ml) and (. + -.) -1-phenylethylamine (1.089g, 9.0mmol) were placed. A Kugelrohr bulb was attached to the flask as a condenser, and the mixture was refluxed for 7 hours under a nitrogen atmosphere. Upon backflow, a few drops of water are deposited on the inner wall of the bulb. Thin layer chromatography showed that all starting material was consumed, yielding a single less polar product. The mixture was cooled in an ice bath to give a viscous insoluble material. The solvent was removed under vacuum and the product was taken up on 15cc of silica gel with 50cc of ethyl acetate. The solvent was removed under reduced pressure, and the absorbed substance was placed on the top of the column and eluted with ethyl acetate/hexane 1:1 (solvent: ethyl acetate/hexane 1: 1). The fractions containing pure material were concentrated to give the solid product, which was recrystallized from isooctane (yield 0.501g, 29%). Melting point: 85-87 ℃.1H-NMR (CDCl)₃,400MHz):δ＝1.82(dd,3H),2.59-2.67(m,1H),2.94-3.05(m,1H),4.49-4.57(m,1H),5.40(q,1H),7.27-7.44(m,5H).13C-NMR(CDCl₃,100MHz):δ＝16.5,16.6,37.0,37.1,50.5,50.7,66.7,127.5,127.5,128.0,128.5,128.6。

(R) - (+) -alpha-methylbenzylimide (6 a') of D- (+) -malic acid (6)

In a 100ml recovery flask with a stirring bar, D- (+) -malic acid (1.056g, 8.0mmol), xylene (20ml) and R- (+) - α -methylbenzylamine (1.089g, 9.0mmol) were placed. The flask was equipped with a Dean Stark apparatus, reflux condenser and nitrogen inlet. The mixture was refluxed for 8 hours. After this time, TLC indicated that all starting material was consumed, yielding a single less polar material, so the mixture was cooled in an ice bath. Upon cooling, a viscous mass appeared which was insoluble in xylene. The solvent was removed under vacuum and the product was taken up in 50cc EtOAc on 20cc silica gel. The solvent was removed and the absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:1 (solvent: ethyl acetate/hexane 1: 1). The fractions were concentrated to give the solid product, which was recrystallized from isooctane (yield 0.595g, 34%). Melting point: 102-103 ℃.1H-NMR (400MHz): δ ═ 1.81(d,3H),2.62(dd,1H),3.00(dd,1H),3.26(s,1H, -OH)4.47-4.51(m,1H),5.40(q,1H),7.27-2.34(m,5H).13C-NMR (100MHz): δ ═ 16.6,37.1,50.5,66.7,127.5(2xC),128.0,128.5(2xC),139.0,173.7,178.2.

Benzoyl ester of 6a (6b) prepared from racemic α -methylbenzylamine

In a 100ml recovery flask with a stir bar, the imide (0.250g, 1.14mmol, anhydrous pyridine (10ml) is placed, the mixture is stirred in an ice bath under nitrogen until all imide is dissolved, the ice bath is removed and benzoyl chloride (0.280g,2.0mmol) is added dropwise, the mixture is stirred at room temperature overnight thin layer chromatography shows all starting materials are consumed, a single less polar product is obtained, the reaction is quenched by addition of ice cold water, the resulting precipitate is isolated by suction filtration, washed with water and air dried, the product is absorbed on 15cc of silica gel with 50ml of ethyl acetate, the solvent is evaporated to dryness, the absorbed material is placed on top of a silica gel column, eluted with ethyl acetate/hexane 1:3 (solvent: ethyl acetate/hexane 1:3), the fractions are concentrated to give a solid product, the base is recrystallized from isooctane (yield 0.243g, 66%). Melting point: 109 ℃ and 111 ℃.1H-NMR (CDCl)₃,400MHz):δ＝1.87(dd,3H),2.74-2.84(m,1H),3.17-3.26(m,1H),5.47-5.65(m,2H),7.32-7.68(m,7H),8.03-8.06(m,2H).13C-NMR(CDCl₃,100MHz):δ＝16.6,16.7,35.8(2xC),50.8,50.1,67.7,67.8,127.6,127.7,128.0,128.5,130.0,133.8,139.0,139.2,165.5,172.8,173.1。

S- (-) - α -methylbenzylimide of malic acid (6) (6 a')

Into a 200ml recovery flask with a stirring bar were placed D- (+) -malic acid (2.680g, 20.0mmol), xylene (100ml) and S- (-) - α -methylbenzylamine (2.662g, 22.0 mmol). The flask was fitted with a Dean Stark trap, reflux condenser and nitrogen inlet. The mixture was refluxed for 8 hours and the water formed during the reaction was removed with a Dean Stark trap. Thin layer chromatography showed that all starting material was consumed, yielding a single less polar product. The flask was cooled in an ice bath and the resulting precipitate was isolated, washed with ether, air dried and recrystallized from 1-PrOH (yield 3.302g, 75%). Melting point: 179 ℃ and 182 ℃.1H-NMR (DMSO-d6, 400MHz). delta. ═ 1.48(d,3H),2.32(dd,1H),2.51(dd,1H),3.87(dd,1H),4.39(q,1H),7.35-7.46(m, 5H).13C-NMR (DMSO-d6, 100MHz). delta. ═ 21.4,42.34,50.4,66.48,127.1,128.7,128.8,128.9,129.1,140.2,172.8,177.3.

6a "para-butylbenzoyl ester (6c)

In a 100ml recovery flask with a stirring bar were placed (S) -3-hydroxy-1- (1-phenylethyl) -pyrrolidine-2, 5-dione (0.329g, 1.5mmol), 2-methylpyridine (10ml) and p-butylbenzoyl chloride (0.393g, 2.0 mmol). The mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. After this time, TLC indicated the appearance of a new less polar product. N-butylbenzoyl chloride (0.196gm, 1.0mmol) was again added and the mixture was stirred at room temperature overnight to ensure completion of the reaction. Then, ice-cold water was added dropwise with stirring. The resulting precipitate was isolated by suction filtration, washed with water and air dried. The product was taken up with 50ml of ethyl acetate on 15cc of silica gel and the solvent was removed under reduced pressure. Placing the absorbed material on top of a silica gel columnEthyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1:9 first, then the polarity of the solvent was gradually increased to 1: 3). The fractions were concentrated to give a solid product which was recrystallized from isooctane (yield 0.080g, 14%). Melting point: 123 ℃ and 124 ℃.1H-NMR (CDCl)₃,100MHz):δ＝0.92(t,3H),1.29-1.38(m,5H),1.55-1.65(m,5H),2.64(dd,2H),5.30-5.37(m,1H),6.32(d,1H),7.21-7.70(m,9H).13C-NMR(CDCl₃,400MHz):δ＝13.9,14.1,21.7,22.3,22.7,29.4,29.7(2xC),31.9,33.4,35.5,49.1,126.3,126.9,127.4,128.6(2xC),128.7,131.9(2xC),143.2,146.9,166.5。

Benzylimides (6D) of D- (+) -malic acid (6)

In a 200ml recovery flask with a stirring bar, D- (+) -malic acid (3.350g, 25.0mmol), xylene (100ml) and benzylamine (2.889g, 27.0mmol) were placed. The flask was fitted with a Dean Stark trap, reflux condenser and nitrogen inlet. The mixture was refluxed for 8 hours and the water formed during the reaction was removed with a Dean Stark trap. Thin layer chromatography showed that all starting material was consumed, yielding a single less polar product. The flask was cooled to room temperature and then placed under low vacuum. The resulting residue was then absorbed on 15cc of silica gel, and the absorbed material was placed on top of the silica gel column, eluting with ethyl acetate/hexane 1:1 (solvent: ethyl acetate/hexane 1: 1). The fractions were concentrated to give the solid product, which was recrystallized from isooctane/MeOH (yield 1.948g, 38%). Melting point: 102-103 ℃.1H-NMR (CDCl)₃,400MHz):δ＝7.29-7.41(m,5H),4.63-4.72(m,3H),3.05(dd,1H),2.71(dd,1H).13C-NMR(CDCl₃,100MHz):δ＝178.0,173.8,135.2,128.9(2xC),128.8(2xC),128.2,67.0,42.5,37.1。

p-Butylbenzoyl ester prepared from 6 a' (6e)

In a 100ml recovery flask with a stirring bar, 3-hydroxy-1- (1-phenylethyl) -pyrrolidine-2, 5-dione (0.329g, 1.5mmol), pyridine (10ml) and p-butylbenzoyl chloride (0.393g, 2.0mmol) were placed. The mixture was stirred at room temperature under a nitrogen atmosphere overnight. After this time, thin layer chromatography indicated the appearance of a new less polar product. Then, ice-cold water was added dropwise with stirring. The resulting precipitate was isolated by suction filtration, washed with water and air dried. Thin layer chromatography of the crude product showed two spots (one was butylbenzoyl chloride and the other was the new product). The crude product is then taken up in 50ml of ethyl acetate on 15cc of silica gel and the solvent is removed under reduced pressure. The absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1:9 first, then the polarity of the solvent was gradually increased to 1: 4). The fractions were concentrated to give the pure solid product. It was recrystallized from isooctane (yield 0.282g, 50%). Melting point: 67-69 ℃.1H-NMR (CDCl)₃,400MHz):δ＝7.94-7.96(m,2H),7.24-7.50(m,7H),5.20-5.56(m,2H),3.21(dd,1H),2.76(dd,1H),2.67(t,2H),1.87(d,3H),1.57-1.65(m,2H),1.32-1.39(m,2H),0.93(t,3H).13C-NMR(CDCl₃,100MHz):δ＝13.9,16.6,22.3,33.2,35.8(2xC),50.8,67.7,125.9,127.7(2xC),128.0,128.5(2xC),128.6(2xC),130.1(2xC),139.0,149.7,165.6,172.9,173.3。

6d para-butylbenzoyl ester (6f)

In a 100ml recovery flask with stirring bar, 1-benzyl-3-hydroxy-pyrrolidine-2, 5-dione (0.308g, 1.5mmol), pyridine (10ml) and p-butylbenzoyl chloride (0.589g, 2.0mmol) were placed. The mixture was stirred at room temperature under a nitrogen atmosphere overnight. Thin layer chromatography indicated complete consumption of starting material and then cold water was added dropwise with stirring to fill the flask. No precipitate was observed even after acidification, so the product was extracted with ethyl acetate (25X 3 ml). The solvent was removed by rotary evaporator and the solid product was taken up on 15cc of silica gel with 50ml of ethyl acetate. The ethyl acetate was removed under reduced pressure and,and the absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1:9, solvent polarity was gradually increased to 1: 3). The fractions were concentrated to give the solid product, which was recrystallized from isooctane (yield 0.440g, 80%). Melting point: 76-78 ℃.1H-NMR (CDCl)₃,400MHz):δ＝7.94-7.96(m,2H),7.25-7.44(m,7H),5.64-5.67(m,1H),4.71-4.79(m,2H),3.27(dd,1H),2.81(dd,1H),2.67(t,2H),1.56-1.63(m,2H),1.32-1.37(m,2H),0.93(t,3H).13C-NMR(CDCl₃,100MHz):δ＝173.2,173.0,165.6,149.8,135.2,130.1(2xC),129.0(2xC),128.8(2xC),128.7(2xC),128.2,125.8,67.8,42.8,36.0,35.8,33.2,22.3,13.9。

Phenethylimide of D- (+) -malic acid (6) (6g)

Into a 200ml recovery flask with a stir bar were placed D- (+) -malic acid (3.35g, 25.0mmol), m-xylene (75ml) and phenethylamine (3.03g, 25.0 mmol). The flask was equipped with a solvent stripper, condenser and nitrogen inlet, the stripper was filled with xylene (-25 ml). The mixture was gradually heated to reflux, kept at this temperature overnight, and then xylene (-50 ml) was removed. The mixture was cooled with stirring and toluene (20ml) was added. The mixture was stirred in an ice bath; the solid was isolated by suction filtration, washed with cold toluene and air dried. Yield 4.26gm (78%). Melting point: 131 ℃ and 133 ℃.1H-NMR (CDCl)₃,400MHz):δ＝2.62(dd,1H),2.89(t,2H),3.01(dd,1H),3.75(t,2H),4.54(dd,1H),7.18-7.35(m,5H).13C-NMR(CDCl₃,100MHz):δ＝178.1,173.8,137.4,128.8,128.6,126.8,66.8,40.0,37.1,33.4。

6g of benzoyl ester (6h)

In a 100ml recovery flask, imide (1.08g, 5.0mmol) and anhydrous pyridine were placed. The mixture was stirred under nitrogen until all dissolved, thenIt was then cooled in an ice bath. Benzoyl chloride (0.84g, 6.0mmol) was added dropwise, the mixture was stirred and allowed to warm to room temperature overnight. The next day, the mixture was cooled in an ice bath and water was added dropwise to fill the flask with stirring. The resulting solid was collected by suction filtration, washed with water and air dried. The product was dissolved in boiling 1-propanol, filtered through a corrugated filter paper and the filtrate was allowed to cool. The product was in the form of very small needles, which were collected by suction filtration, washed with cold 1-propanol and air-dried. Yield 1.28g, 79%. Melting point: 145-146 ℃.1H-NMR (CDCl)₃,400MHz):δ＝2.74(dd,1H),2.96(ddd,2H),3.21(dd,1H),3.84(ddd,2H),5.58(dd,1H),7.22-7.65(m,8H),8.05(d,2H).13C-NMR(CDCl₃,100MHz):δ＝33.3,35.8,40.2,67.9,126.8,128.5,128.6,128.8,130.0,133.9,137.5,165.5,173.0,173.2。

6g of p-trifluoromethylbenzoyl ester (6i)

In a 100ml recovery flask, imide (1.08g, 5.0mmol) and anhydrous pyridine were placed. The mixture was stirred under nitrogen until all dissolved and then cooled in an ice bath. Subsequently, 4-trifluoromethylbenzoyl chloride (1.250g, 6.0mmol) was added dropwise, and the mixture was stirred briefly in an ice bath and at room temperature for 5 hours. Water (8 drops) was added and the mixture was stirred at room temperature for 1 hour, then water was added dropwise to fill the flask. The resulting solid was collected by suction filtration, washed with water and air dried. It was recrystallized from 1-propanol to give the product as a white solid. Yield 1.51g, 77%. Melting point: 128-129 ℃.1H-NMR (CDCl)₃,400MHz):δ＝2.75(dd,1H),2.97(ddd,2H),3.23(dd,1H),3.85(ddd,2H),5.60(dd,1H),7.22-7.33(m,5H),7.73(d,2H),8.15(d,2H).13C-NMR(CDCl₃,100MHz):δ＝33.3,35.7,68.2,125.6,125.7,126.9,128.6(2xC),128.9(2xC),130.5(2xC),131.7,135.5,137.3,164.3,172.7,172.8。

P-methoxyanilide of malic acid (6) (6j)

In a 200ml recovery flask with a stirring bar, D- (+) -malic acid (3.350g, 25.0mmol), m-xylene (75ml) and p-anisidine (3.210g, 26.1mmol) were placed. The flask was equipped with a solvent stripper, condenser and nitrogen inlet. The mixture was gradually heated to reflux in an oil bath and maintained at reflux for 4 hours. During this time, the xylene and water were gradually removed, leaving only xylene (-30 ml). The mixture was cooled and the remaining xylene was removed under low vacuum overnight. To the solid residue was added isopropanol (100ml) and the mixture was boiled and stirred, then gradually cooled to room temperature and finally stirred in an ice bath. The grey precipitate was isolated by suction filtration, washed with some cold isopropanol and air dried. Yield: 4.40g, 80%. Melting point: 175 ℃ and 178 ℃.1H-NMR (DMSO-d6,400MHz): δ ═ 2.60(dd,1H),3.11(dd,1H),3.79(s,3H),6.18(dd,1H),7.10(dd,4H), 13C-NMR (DMSO-d6,100MHz): δ ═ 38.4,55.8,66.9,114.6,121.0,121.6,125.3,128.6,159.3,174.7,178.1.

N-butyl-apple imide (6k)

Into a 200ml recovery flask with a stir bar were placed D- (+) -malic acid (5.360g, 40.0mmol), m-xylene (50ml) and 1-aminobutane (2.940g, 25.0 mmol). The flask was equipped with a solvent stripper, condenser and nitrogen inlet, and the stripper was filled with xylene (-25 ml). The mixture was gradually heated to reflux (the reaction was not immediately set to full boiling due to the relatively volatile amine). After the 1 st hour of reflux, water and xylene (50ml) were removed stepwise over the next 4 hours. The resulting mixture was cooled to room temperature and left overnight under low vacuum to remove residual solvent. 1H-NMR (CDCl)₃,400MHz):δ＝0.943(t,3H),1.34(m,2H).1.57(m,2H),2.69(dd,1H),3.07(dd,1H),3.53(t,2H),4.65(dd,1H).13C-NMR(CDCl₃,100MHz):δ＝13.6,20.0,29.6,37.1,38.8,66.9,174.2,178.1。

Preparation of Nootkatone (8) from Valencene (7)

A250 ml round bottom flask containing anhydrous pyridine (50ml) was cooled to (-15 ℃) in an ice salt bath under a nitrogen atmosphere. Next, CrO was added over 5 minutes through a cellophane cone inserted into the neck of the flask₃(4.74g, 30.0 mmol). Stirring was continued for 6 hours during which time no more ice was added to the bath. The initially formed bright yellow viscous mixture gradually turned into a bright red crystalline slurry. Then, valencene (4.0g, 20.0mmol) was added to the mixture at room temperature. After stirring for 25 hours, the mixture became a dark red oil. The reaction was checked by GC-MS and the product peaked at 218.0 was obtained. The reaction was terminated and the solvent was evaporated under vacuum. Separation was performed through a silica gel column with 90% hexane and 10% ethyl acetate and eluted with a gradient up to 25% ethyl acetate. The fractions containing the product were evaporated to give a yellow oil. Upon checking by TLC, some impurities were present in the final product. The product was isolated by passing through a silica gel column with 90% hexane and 5% ethyl acetate to give a yellow oil. Yield-1.41 g (44%). The product is: 4-alpha, 5-dimethyl-1, 2,3,4,4 alpha, 5,6, 7-octahydro-7-one-3-isopropenylnaphthalene.¹HNMR(400MHz,CDCl₃)δ0.990(3H,d),1.134(3H,s),1.356(2H,ddt),1.753(3H,s),2.000(2H,dddd),2.268(1H,dddd),2.351(2H,dd),2.406(1H,dt),2.561(2H,ddt),4.760(2H,d),5.785(1H,s)。¹³CNMR(400MHz,CDCl₃)δ16.3,20.6,30.1,31.5,35.8,38.3,40.7,41.9,110.0,123.9,147.9,168.6,197.5。GC-Ms-218.2

Preparation of 2- (4-butylbenzoyloxy) valencene from 7 (7a)

In a 100ml round bottom flask, Cu-Al-Ox (30mg) was dissolved in acetonitrile (2ml) under an open atmosphere. Next, p-n-butylbenzoic acid (0.83g, 5.0mmol) was added to the system, and the mixture was stirred for 10 minTo dissolve the acid. Then valencene (1.02g, 5.0mmol) and TBHP (0.13g, 1.5 equiv.) were added. The reaction mixture was stirred at 82 ℃ for 24 hours. After 24 hours, the mixture was checked by TLC, and there were two new products and some starting material. More valencene (0.51g, 2.5mmol) and TBHP (0.064g, 0.75 eq) were then added and the reaction was allowed to proceed for an additional 12 hours. After this time, the reaction mixture was checked by TLC and some starting material was present in the mixture and stirred for an additional 6 hours. After 12 hours the mixture was checked by TLC and the same amount of starting material was present in the mixture. The reaction was terminated. Adding saturated Na₂SO₃Aqueous solution (5ml), the solution mixture was extracted with ethyl acetate, washed with saturated EDTA solution (5ml), and dried over anhydrous Na₂SO₄And (5) drying. The mixture was then filtered through silica and the solvent was removed using rotary evaporation. Separation was performed by silica gel column with 95% hexane and 5% ethyl acetate. Some impurities are present due to hexane. And then separated by passing through a silica gel column with 100% pure hexane. The product was obtained as a colorless oil. For further discussion see garcia-Cabeza, a.l.; mari i n-Barrios, R.; Moreno-Dorado, f.j.; ortega, m.j.; massanet, g.m.; guerra, F.M. Allyllic Oxidation of Alkenes Catalyzed by a hopper-Aluminum Mixed oxide. org.Lett.2014,16(6), 1598-1601.

Yield-0.264 g (14.0%).¹HNMR(400MHz,CDCl₃)δ0.89(3H,t),0.96(3H,d),1.13(3H,s),1.76(3H,s),2.70(H,t),4.76(2H,d),5.33(1H,d),5.61(H,ddd),7.28(2H,ddd),8.01(2H,ddd)。¹³CNMR(400MHz,CDCl₃)δ13.8,15.6,18.4,20.8,22.3,25.9,27.1,32.7,33.1,33.2,35.6,35.7,40.9,41.0,44.9,68.2,108.2,109.2,120.1,128.5,129.6,130.2,149.3,171.6。

Preparation of 2- (4-Butoxybenzoyloxy) valencene from 7 (7b)

In a 100ml round bottom flask, Cu-Al-Ox (300mg) was dissolved in acetonitrile (20ml) under an open atmosphere. Next, p-butoxybenzoic acid (0.97g, 5.0mmol) was added to the system, andthe mixture was stirred for 10 minutes to dissolve the acid. Then valencene (1.02g, 5.0mmol) and TBHP (0.675g, 1.5 equiv.) were added. The reaction mixture was stirred at 82 ℃ for 24 hours. After 24 hours, the mixture was checked by TLC, and there were two new products and some starting material. Then valencene (0.102g, 0.1mmol) and TBHP (0.067g, 0.1 equiv.) were added and continued for an additional 24 hours. After 24 h, the reaction mixture was checked by TLC for the presence of some starting material in the mixture, and valencene (0.102g, 0.1mmol), TBHP (0.067g, 0.1 equiv.) and Cu-Al-Ox (30mg) were added with acetonitrile (2 ml). After 24 hours the mixture was checked by TLC and the same amount of starting material was present in the mixture. By adding Na₂SO₃The reaction was terminated with an aqueous solution (10ml), and the mixture was extracted with ethyl acetate, washed with a saturated EDTA solution (5ml), and dried over anhydrous Na₂SO₄And (5) drying. The mixture was filtered through silica and the solvent was removed by rotary evaporation. The separation was carried out by silica gel column using 95% hexane and 5% ethyl acetate, but NMR showed that the impurities were mainly in the region of delta 1.0-2.5. The separation was carried out again by means of a silica gel column using 98% pure hexane and 2% ethyl acetate. A colorless oily product was observed. Yield-0.09 g (4.5%).¹HNMR(400MHz,CDCl₃)δ0.90(3H,t),0.97(3H,d),1.14(3H,s),1.76(3H,s),4.02(2H,t),4.73(2H,d),5.36(1H,d),5.63(H,ddd),6.92(2H,ddd),8.01(2H,ddd)。¹³CNMR(400MHz,CDCl₃)δ13.8,16.3,19.3,20.6,20.8,30.2,31.1,31.7,35.2,36.0,38.4,38.6,40.8,67.8,68.9,110.0,114.4,114.4,120.0,122.1,132.0,132.0,148.1,152.3,160.5,165.6。

Preparation of 2- (4-methoxybenzoyloxy) valencene from 7 (7c)

In a 100ml round bottom flask, Cu-Al-Ox (300mg) was dissolved in acetonitrile (20ml) under an open atmosphere. Anisic acid (0.83g, 5.0mmol) was added to the system and the mixture was stirred for 10 minutes to dissolve the anisic acid. Then valencene (1.53g, 5.0mmol) and TBHP (0.739g, 1.5 equiv.) were added. The reaction mixture was stirred at 82 ℃ for 24 hThen (c) is performed. After 36 hours, the mixture was checked by TLC, and there were two new products and some starting material. The reaction was terminated according to previous experience. Adding saturated Na₂SO₃Aqueous solution (5ml), the mixture was extracted with ethyl acetate, washed with saturated EDTA solution (5ml), and dried over anhydrous Na₂SO₄And (5) drying. The mixture was then filtered through silica and the solvent was removed by rotary evaporation. Separation was performed by silica gel column using 95% hexane and 5% ethyl acetate. After evaporation of the solvent, a colorless oil was obtained. The column separation was carried out again by passing through a silica gel column using 95% pure hexane and 5% ethyl acetate. Yield-0.433 g (24.4%).¹HNMR(400MHz,CDCl₃)δ0.91(3H,d),0.97(3H,s),1.58(10H,dddd),1.73(2H,ddd),1.95(1H,ddd),3.88(3H,s),4.73(2H,s),5.36(1H,d),5.59(1H,ddd),6.93(2H,ddd)8.03(2H,dd)。¹³CNMR(400MHz,CDCl₃)δ16.8,18.1,20.8,32.7,33.1,35.8,40.5,44.4,55.4,68.0,108.6,113.4,117.9,120.3,123.5,131.6,150.1,150.7,163.1,166.0。

Preparation of Malononitrile adduct (8a) from Nocardiane (8)

In a 100ml round bottom flask, nocardone (0.5g, 2.2mmol), malononitrile (1.5g, 22.7mmol), anhydrous potassium fluoride (0.4g, 6.8mmol) and ethylene glycol (8ml) were dissolved in DMF and stirred for 3 hours. The reaction mixture was then checked by TLC, and there were two new products with some starting material. The reaction mixture was stirred for an additional two hours. After two hours, no starting material remained and the reaction was terminated. The mixture was extracted with water and ethyl acetate to give a bright red crude product. Separation through a silica gel column using 95% hexane and 5% ethyl acetate gave a yellow oil as the product. Yield-0.34 g (50.6%).¹HNMR(400MHz,CDCl₃)δ1.02,1.04(3H,d),1.09(3H,s),1.28(3H,s),1.586(H,dd),1.73(1H,dddd),1.76(1H,dddd),2.01(H,dd),2.356(1H,dddd),2.41(1H,qdd),2.57(H,dd)2.82(H,dd),4.74(1H,d),4.78(1H,d),6.527(1H,s).¹³CNMR(400MHz,CDCl₃)δ16.8,18.1,20.8,32.7,33.1,35.8,40.5,44.4,55.4,68.0,108.6,113.4,117.9,120.3,123.5,131.6,150.1,150.7,163.1,166.0。

The optical and physical properties of the synthetic materials associated with flexible filter applications were evaluated in LC formulations. Important material properties of this approach are described herein. Among those listed, the pitch was used as a screening parameter to determine if the liquid crystal formulation is suitable for further characterization tests. If the pitch passes (i.e., the measurement is in the visible wavelength region) the preliminary screening, then other relevant characteristics will be selected for further evaluation.

Host material

Two nematic host materials for evaluation of biological target derivatives were used: pure nematic 5CB and commercial nematic mixture E7, as shown below. The first was 5CB, a pure substance 4-cyano-4' -pentylbiphenyl. 5CB is a common nematic phase of formula C18H 19N. The nematic temperature ranges from 18 ℃ to 35 ℃. The second is E7, a commercial mixture containing cyanobiphenyl and cyanobiphenyl components. The composition is shown in fig. 3. The nematic temperature ranges from-10 ℃ to 60 ℃. The above synthesized biologically available derivatives were mixed as chiral dopants (twisters) with these nematic host materials in different concentrations. The pitch and helical twisting power of these cholesteric liquid crystal formulations are screened to obtain a system with a pitch in the visible wavelength region.

Betulin 4-Butylbenzoic acid diester (5o)

In a 100ml recovery flask with a stir bar, betulin (0.443g, 1.0mmol), anhydrous dichloromethane (10ml), n-butylbenzoyl chloride (0.558g, 3.0mmol), pyridine (10ml) and 4-dimethylaminopyridine (0.366g, 3.0mmol) were placed. The mixture was protected under nitrogen atmosphere andheated at 55 ℃ for 5 hours. After this time, thin layer chromatography indicated that two new products were formed. Additional pyridine (3.0ml), 4-dimethylaminopyridine (0.122g, 1.0mmol) and p-butylbenzoyl chloride (0.392g, 2.0mmol) were added and the mixture was stirred at 55 ℃ overnight. After this time, thin layer chromatography indicated complete consumption of the starting material, resulting in a single less polar product. Then cold water (50ml) and 10% HCl (5ml) were added dropwise with stirring. The product was extracted with ethyl acetate (3X 25ml), washed with water and over anhydrous MgSO₄And (5) drying. The solvent was evaporated and the resulting liquid was absorbed on 20cc of silica gel with 50ml of ethyl acetate. After concentration to dryness, the absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1: 9). Concentrating the fractions to obtain a solid product, which is separated from 1-PrOH/H₂Recrystallisation from O (yield 0.410g, 54%). Melting point: 69-71 ℃.1H-NMR (CDCl)₃,400MHz):δ＝7.93-7.97(m,4H),7.23-7.26(m,4H),2.68-4.72(m,2H),4.61-4.62(m,1H),4.51(d,J＝10.8Hz,1H),4.07(d,J＝11.0Hz,1H),2.63-2.68(m,4H),2.50-2.57(m,1H),1.72(s,3H),1.08(s,3H),1.02(s,3H),0.99(s,3H).13C-NMR(CDCl₃,100MHz):δ＝167.1,166.4,150.2,148.5,148.3,129.6,129.6,128.5,128.4,128.4,127.9,109.9,81.3,63.1,55.5,50.3,48.9,47.8,46.7,42.8,40.9,38.4,38.2,37.7,37.1,35.7,34.8,34.1,33.3,30.0,29.7,29.7,29.6,28.1,27.1,25.2,23.8,22.3,20.8,19.2,18.2,16.8,16.2,16.1,14.8,,13.9.IR(cm^-1):2926,2868,1714,1610,1455,1269,1176,1105,971。

Betulin 4-heptylbenzoic acid diester (5p)

Into a 200ml recovery flask with a stir bar were placed betulin (2.215g, 5.0mmol), anhydrous dichloromethane (25ml), p-heptylbenzoyl chloride (4.780g, 20.0mmol), pyridine (25ml) and 4-dimethylaminopyridine (1.830g, 15.0 mmol). The mixture was protected under nitrogen and heated at 55 ℃ overnight. Thereafter, thin layer chromatography indicated complete consumption of betulin, resulting in a single less polar product and some unreversedThe corresponding acid chloride. Then cold water (50ml) and hydrazine solution (10% v/v, 10ml) were added dropwise and the mixture was stirred at room temperature for an additional 25 minutes to remove excess acid chloride from the mixture. The product was extracted with ethyl acetate (3X 25ml), washed with water and over anhydrous MgSO₄And (5) drying. The solvent was evaporated and the resulting liquid was taken up in 50ml of ethyl acetate on 30cc of silica gel. After concentration to dryness, the absorbed material was placed on top of a silica gel column and eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1: 9). The product containing fractions were concentrated to give a viscous liquid which was pure by 1H-NMR. The yield was 3.758g, 89%. 1H-NMR (CDCl)₃,400MHz):δ＝7.93-7.97(m,4H),7.22-7.26(m,4H),4.61-4.70(m,2H),4.51(d,J＝10.8Hz,1H),4.31(t,J＝6.6Hz,1H),4.07(d,J＝11.2Hz,1H),2.63-2.68(m,4H),2.49-2.56(m,1H),1.56(s,3H),1.08(s,3H),1.02(s,3H),0.99(s,3H).13C-NMR(CDCl₃,100MHz):δ＝167.1,166.4,150.2,148.5,148.3,129.6,129.6,128.4,128.3,127.9,109.9,81.3,64.6,63.1,55.5,50.3,48.9,47.8,46.7,42.8,41.0,38.4,37.7,37.1,36.0,34.8,34.2,31.8,31.2,30.8,30.3,30.0,29.7,29.2,29.1,28.1,27.1,25.2,23.8,22.6,20.9,19.3,19.2,18.2,16.8,16.2,16.1,14.8,14.1,13.8.IR(cm^-1):2924,2854,1713,1456,1269,1175,1105,1018,970。

Betulol 2-ethylhexanoic acid diester (5q)

In a 100ml recovery flask with stirring bar, betulin (0.886g, 2.0mmol), anhydrous dichloromethane (10ml), 2-ethylhexanoyl chloride (1.134g, 7.0mmol), pyridine (10ml) and 4-dimethylaminopyridine (0.366g, 3.0mmol) were placed. The mixture was protected under nitrogen and heated at 55 ℃ overnight. After this time, TLC indicated complete consumption of starting material to give a single less polar product. Then cold water (50nl) and 10% HCl (10ml) were added dropwise with stirring. The product was extracted with EtOAc (3X 25ml), washed with water and over anhydrous MgSO₄And (5) drying. The solvent was evaporated and the resulting liquid was absorbed on 20cc of silica gel with 50ml of ethyl acetate. Concentrating to dryness, and placing the absorbed material inAt the top of the silica gel column, it was eluted with ethyl acetate/hexane 1:9 (solvent: ethyl acetate/hexane 1: 9). The product containing fractions were concentrated to give a viscous liquid which was pure by 1H-NMR. Yield 1.197g, 86%.¹HNMR(CDCl₃,400MHz):δ＝4.68(d,J＝1.9Hz,1H),4.58-4.59(m,1H),4.45-4.49(m,1H),4.28(d,J＝11.1Hz),3.81(d,J＝11.1Hz),2.41-2.48(m,1H),2.17-2.39(m,3H),1.04(s,3H).13C-NMR(CDCl₃,100MHz):δ＝176.8,176.1,109.8,80.4,62.4,55.4,50.3,48.8,47.7,47.9,47.7,47.6,46.4,42.7,40.9,38.3,37.8,37.6,37.0,34.7,34.1,32.0,31.8,31.6,29.9,29.7,29.7,29.6,28.0,27.0,25.7,25.5,25.5,25.2,23.8,22.6,20.8,19.1,18.2,16.6,16.1,16.0,14.8,14.1,13.9,11.9.IR(cm^-1):2930,2870,1728,1457,1377,1173,1142,978,882。

For HTP measurements, the flat glass plate and cylindrical lens were cleaned and coated with polyimide. The polyimide alignment layers on both surfaces were rubbed unidirectionally with velvet fabric. A lens is then placed on the flat glass substrate and a small amount of sample mixture is placed on the substrate, as close as possible to the center of the lens. Capillary action then ensures that the sample liquid covers the cylindrical Cano wedge box (wedge), the lens and the substrate. The director field relaxes over time and the disclination lines form concentric circles around the axis of symmetry of the lens. The resulting pattern was observed and photographed in a polarization microscope. The images were then analyzed by MatLab and the ring spacing was determined by analysis. The pitch of the rings together with the radius of the lens gives the pitch P of the sample. The HTP can be determined by repeated measurements of samples having different dopant concentrations. The helical twisting force was measured and the results are summarized in table 1 below.

TABLE 1