阅读说明：本技术 黄酮、异黄酮类化合物的制备方法及其应用 (Preparation method and application of flavone and isoflavone compounds ) 是由 周强辉 马园园 于 2021-09-18 设计创作，主要内容包括：本发明提供一种黄酮类、异黄酮类化合物的制备方法,反应式如下所示：所述制备方法具体包括如下步骤：在惰性气体氛围下,以式A所示化合物、B和C为起始原料,在钯催化剂D、膦配体E、降冰片烯F和碱G的作用下,在溶剂H中搅拌反应,分离,即可得到所述黄酮类、异黄酮类化合物M、J、K或L。该方法涉及的主要原料均为商品化试剂,价格低廉,催化剂为降冰片烯衍生物,相比于现有技术中的类似反应使用的催化剂降冰片烯,其用量大大减少,降低了制备成本,适于工业化生产。本发明还提供制备得到的黄酮类、异黄酮类化合物在制备umbralisib核心骨架中的应用。(The invention provides a preparation method of flavonoid and isoflavone compounds, which has the following reaction formula:)

1. A method for preparing flavonoid and isoflavone compounds is characterized in that the reaction formula is as follows:

wherein the structural formula of the flavonoid and isoflavonoid compounds is selected from one of a compound shown in a formula M, a compound shown in a formula J, a compound shown in a formula K and a compound shown in a formula L; b is an aryl halide; c is an alkene or alkyne; r¹One selected from aryl, alkyl, alkoxy and halogen, m is selected from 0,1 and 2, and X is selected from O or S; r²Is one of alkyl, ester group, nitro, amido, sulfonyl, alkoxy and halogen; n is selected from 1 and 2; p is selected from 0,1, 2 and 3; r³And R⁴Each independently selected from one of aryl, heterocyclic aryl, alkyl, ester group, silicon group, amide group, sulfonyl, phosphino group, alkoxy and hydrogen; r⁵Is silicon base; r⁶Is one of alkyl, sulfydryl, alkoxy, p-methyl benzene sulfonyloxy and halogen; r is taken from 0,1, 2; r⁷Selected from hydrogen, heterocyclesOne of aryl, alkyl, ester group, hydroxyl, cyano, alkoxy and halogen;

the preparation method specifically comprises the following steps: under the inert gas atmosphere, taking a compound shown as a formula A, B and C as initial raw materials, stirring and reacting in a solvent H under the action of a palladium catalyst D, a phosphine ligand E, norbornene F and an alkali G, and separating to obtain the flavonoid and isoflavone compounds.

2. The method for preparing flavonoids and isoflavones according to claim 1, wherein the structural formula B is

Wherein Y is iodine, bromine or p-toluenesulfonyloxy.

3. The method for preparing flavonoids and isoflavones according to claim 1, wherein the structural formula C is as follows:

4. a process for preparing flavonoids and isoflavones according to claim 1, wherein the phosphine ligand E is selected from one or more of triarylphosphine, dicyclohexyl (2',4',6' -triisopropyl- [1,1' -diphenyl ] -2-yl) phosphine, dicyclohexyl (2',6' -dimethoxy- [1,1' -diphenyl ] -2-yl) phosphine, 2' - (dicyclohexylphosphino) -N, N-dimethyl- [1,1' -diphenyl ] -2-amine, tris (2-furyl) phosphine, and 2- (di-t-butylphosphino) biphenyl.

5. The method for preparing flavonoids and isoflavonoids compounds according to claim 1, wherein the structural formula of the norbornene derivative F is as follows:

wherein R is⁸、R⁹Each independently is an ester group, a carbonyl group, a cyano group, an amide group or an alkyl group; q is an integer, and q is more than or equal to 0 and less than or equal to 8; s is taken from 0,1, 2.

6. The method for preparing flavonoids and isoflavones according to claim 1, wherein the base G is selected from one or more of sodium carbonate, potassium carbonate, cesium carbonate, potassium acetate, cesium acetate, tripotassium phosphate, potassium bicarbonate and potassium hydroxide.

7. The method for preparing flavonoids and isoflavones according to claim 1, wherein the solvent H is selected from one or more of 1, 4-epoxyhexaalkane, tetrahydrofuran, ethylene glycol dimethyl ether, toluene, acetonitrile, N-dimethylformamide and N-methylpyrrolidone.

8. The method for preparing flavonoids and isoflavones according to claim 1, wherein the reaction temperature is controlled to be 80-140 ℃.

9. The method for preparing flavonoids and isoflavones according to claim 1, wherein the reaction time is controlled to be 18-60 h.

10. The application of flavonoids and isoflavonoids compounds in preparing the umbralisib core skeleton is characterized in that the flavonoids and isoflavonoids compounds are reacted with halogen to obtain the umbralisib core skeleton; the chemical formula of the umbralisib core skeleton is shown as the following formula N:

the flavonoid and isoflavone compound is selected from one of a compound shown as a formula M, a compound shown as a formula J, a compound shown as a formula K and a compound shown as a formula L,

preferably, the flavonoid and isoflavone compound is a compound shown in a formula L;

wherein R is¹One selected from aryl, alkyl, alkoxy and halogen, m is selected from 0,1 and 2, and X is selected from O or S; r²Is one of alkyl, ester group, nitro, amido, sulfonyl, alkoxy and halogen; n is selected from 1 and 2; p is selected from 0,1, 2 and 3; r³And R⁴Each independently selected from one of aryl, heterocyclic aryl, alkyl, ester group, silicon group, amide group, sulfonyl, phosphino group, alkoxy and hydrogen; r⁵Is silicon base; r⁶Is one of alkyl, sulfydryl, alkoxy, p-methyl benzene sulfonyloxy and halogen; r is taken from 0,1, 2; r⁷One selected from the group consisting of a hydrogen atom, a heterocyclic aryl group, an alkyl group, an ester group, a hydroxyl group, a cyano group, an alkoxy group and a halogen; y is iodine, bromine or p-toluenesulfonyloxy;

preferably, the chemical formula of the flavonoid and isoflavone compound in the claim 1 in preparing the umbralisib core skeleton is as follows:

Technical Field

The invention relates to the field of organic synthesis, in particular to a preparation method and application of flavone and isoflavone compounds.

Background

Flavones and isoflavones are a very important class of building blocks, widely found in natural products and drug molecules with biological activity (Eur J Med Chem,2014,84, 206-. At present, methods for synthesizing flavonoids and isoflavonoids are roughly divided into two categories (Chem Rev,2014,114, 4960-4992; Chin Chem Lett,2020,31, 3073-3082; Mini-Rev Org Chem,2016,13, 31-48; Tetrahedron,2012,68, 8523-8538). One is obtained by the Claisen condensation reaction (Med Chem Lett,2012,22, 5455-) -5459), Baker-Venkataraman rearrangement reaction (J Chem Soc,1934,10, 1767-) -1969) and Vilsmeier-Haack ([8] Org Prep Proced Int,2009,41,69-75) of aromatic compounds, but most of the strategies can only construct C2 or C3 monosubstituted chromone compounds. The other is obtained by further derivatization of the chromone structure. However, these methods are generally single tasks and the structural diversity of the obtained flavonoids and isoflavonoids is limited, limiting their range of use.

Therefore, it is important to develop a new and efficient and simple synthesis method for synthesizing flavonoids and isoflavonoids from simple and easily available raw materials.

Disclosure of Invention

Aiming at the problems in the prior art, the invention takes the simple and easily obtained iodo chromone compound as the initial raw material, and the iodo chromone compound is stirred and reacted in the organic solvent at the temperature of 80-140 ℃ under the action of the palladium catalyst, the norbornene derivative, the phosphine ligand and the alkali, so that the flavonoid and the isoflavone compound can be obtained. The method has the advantages of easily available raw materials, simple operation, good chemical selectivity and wide substrate application range, and provides a very efficient and convergent method for synthesizing important drug molecules and natural products containing chromone structural units.

The present invention aims to solve at least one of the technical problems of the prior art to a certain extent, and therefore, in a first aspect of the present invention, the present invention provides a method for preparing flavonoids and isoflavonoids, wherein the reaction formula is as follows:

wherein the structural formula of the flavonoid and isoflavonoid compounds is selected from one of compounds shown in a formula M, compounds shown in a formula J, compounds shown in a formula K and compounds shown in a formula L; b is an aryl halide; c is an alkene or alkyne; r¹One selected from aryl, alkyl, alkoxy and halogen, m is selected from 0,1 and 2, and X is selected from O or S; r²Is one of alkyl, ester group, nitro, amido, sulfonyl, alkoxy and halogen; n is selected from 1 and 2; p is selected from 0,1, 2 and 3; r³And R⁴Each independently selected from one of aryl, heterocyclic aryl, alkyl, ester group, silicon group, amide group, sulfonyl, phosphino group, alkoxy and hydrogen; r⁵Is silicon base; r⁶Is one of alkyl, sulfydryl, alkoxy, p-methyl benzene sulfonyloxy and halogen; r is taken from 0,1, 2; r⁷One selected from the group consisting of hydrogen, heterocyclic aryl, alkyl, ester, hydroxyl, cyano, alkoxy, and halogen;

preferably, R²Is one of methyl, methoxy, ester group, nitro, amido, sulfonyl and halogen; r³And R⁴Each independently selected from one of naphthyl, heterocyclic aryl, alkyl, ester group, silicon group, amide group, sulfonyl, phosphino group, alkoxy and hydrogen; r⁶Is one of alkyl, sulfydryl, alkoxy, p-methyl benzene sulfonyloxy and halogen; r⁷One selected from hydrogen, alkyl, ester group, hydroxyl, cyano, alkoxy, 2-methoxypyridine, thiophene, dibenzothiophene and halogen;

the preparation method specifically comprises the following steps: under the inert gas atmosphere, taking a compound shown as a formula A, B and C as initial raw materials, stirring and reacting in a solvent H under the action of a palladium catalyst D, a phosphine ligand E, norbornene F and an alkali G, and separating to obtain the flavonoid and isoflavone compound M, J, K or L.

In one or more embodiments of the present invention, B is of the formula

Wherein Y is iodine, bromine or p-toluenesulfonyloxy.

In one or more embodiments of the present invention, C has the structural formula:

in one or more embodiments of the present invention, the reaction formula of the preparation method of the flavonoid and isoflavone compound is as follows:

the preparation method of the flavonoid and isoflavone compounds comprises the following steps: under the atmosphere of protective gas, taking a compound shown in formula A, B1 (structural formula shown as above) and C1 (structural formula shown as above) as starting raw materials, stirring in a solvent H under the action of a palladium catalyst D, a phosphine ligand E, a norbornene derivative F and an alkali G, reacting, and separating to obtain the flavonoid compound M or J.

In one or more embodiments of the present invention, the reaction formula of the preparation method of the flavonoid and isoflavone compound is as follows:

the preparation method of the flavonoid and isoflavone compounds comprises the following steps: under the atmosphere of protective gas, taking a compound shown as a formula A, B1 (with a structural formula shown as the above) and C2 (with a structural formula shown as the above) as initial raw materials, stirring the raw materials in a solvent H under the action of a palladium catalyst D, a phosphine ligand E, a norbornene derivative F and alkali G, reacting, and separating to obtain a 2, 3-diaryl substituted chromone compound K, namely the flavonoid and isoflavonoid compound.

In one or more embodiments of the present invention, the reaction formula of the preparation method of the flavonoid and isoflavone compound is as follows:

the preparation method of the flavonoid and isoflavone compounds comprises the following steps: under the atmosphere of protective gas, taking a compound shown as a formula A, B2 (shown as a structural formula) and C2 (shown as a structural formula) as starting raw materials, stirring the starting raw materials in a solvent H for reaction under the action of a palladium catalyst D, a phosphine ligand E, a norbornene derivative F and an alkali G, and separating to obtain the isoflavone compound L.

In one or more embodiments of the present invention, the phosphine ligand E is selected from any one or more of triarylphosphine, dicyclohexyl (2',4',6' -triisopropyl- [1,1' -diphenyl ] -2-yl) phosphine, dicyclohexyl (2',6' -dimethoxy- [1,1' -diphenyl ] -2-yl) phosphine, 2' - (dicyclohexylphosphino) -N, N-dimethyl- [1,1' -diphenyl ] -2-amine, tris (2-furyl) phosphine, 2- (di-t-butylphosphino) biphenyl.

In one or more embodiments of the present invention, the norbornene derivative F has the following structural formula:

wherein R is⁸、R⁹Each independently is an ester group, a carbonyl group, a cyano group, an amide group or an alkyl group; q is an integer, and q is more than or equal to 0 and less than or equal to 8; s is taken from 0,1, 2.

In one or more embodiments of the present invention, the alkali G is selected from any one or more of sodium carbonate, potassium carbonate, cesium carbonate, potassium acetate, cesium acetate, tripotassium phosphate, potassium bicarbonate, and potassium hydroxide.

In one or more embodiments of the present invention, the solvent H is selected from any one or more of 1, 4-epoxyhexaalkane, tetrahydrofuran, ethylene glycol dimethyl ether, toluene, acetonitrile, N-dimethylformamide and N-methylpyrrolidone.

In one or more embodiments of the present invention, the reaction temperature is controlled to be 80 to 140 ℃.

In one or more embodiments of the present invention, the reaction time is controlled to be 18 to 60 hours.

In a second aspect of the present invention, the present invention provides an application of flavonoids and isoflavones in preparing a umbralisib core skeleton, wherein the umbralisib core skeleton is obtained by reacting the flavonoids and isoflavones with halogen; the chemical formula of the umbralisib core skeleton is shown as the following formula N:

the flavonoid and isoflavone compound is selected from one of a compound shown as a formula M, a compound shown as a formula J, a compound shown as a formula K and a compound shown as a formula L,

preferably, the flavonoid and isoflavone compound is a compound shown in a formula L;

wherein R is¹One selected from aryl, alkyl, alkoxy and halogen, m is selected from 0,1 and 2, and X is selected from O or S; r²Is one of alkyl, ester group, nitro, amido, sulfonyl, alkoxy and halogen; n is selected from 1 and 2; p is selected from 0,1, 2 and 3; r³And R⁴Each independently selected from one of aryl, heterocyclic aryl, alkyl, ester group, silicon group, amide group, sulfonyl, phosphino group, alkoxy and hydrogen; r⁵Is silicon base; r⁶Is one of alkyl, sulfydryl, alkoxy, p-methyl benzene sulfonyloxy and halogen; r is taken from 0,1, 2; r⁷One selected from the group consisting of hydrogen, heterocyclic aryl, alkyl, ester, hydroxyl, cyano, alkoxy, and halogen; y is iodine, bromine or p-toluenesulfonyloxy;

preferably, R²Is one of methyl, methoxy, ester group, nitro, amido, sulfonyl and halogen; r³And R⁴Each independently selected from one of naphthyl, heterocyclic aryl, alkyl, ester group, silicon group, amide group, sulfonyl, phosphino group, alkoxy and hydrogen; r⁶Is one of alkyl, sulfydryl, alkoxy, p-methyl benzene sulfonyloxy and halogen; r⁷One selected from hydrogen, alkyl, ester group, hydroxyl, cyano, alkoxy, 2-methoxypyridine, thiophene, dibenzothiophene and halogen;

preferably, the chemical formula of the flavonoid and isoflavonoid compound in the preparation of the umbralisib core skeleton is as follows:

compared with the prior art, the invention has the following advantages and beneficial effects:

1. the invention provides a method for preparing flavonoid and isoflavone compounds, which mainly comprises the raw materials of iodo chromone compounds, aryl or alkyl halides, olefin compounds and aryl potassium trifluoroborate, wherein the raw materials are all commercial reagents, do not need special treatment, have low price or are prepared in large quantities by a simple method.

2. Compared with the catalyst norbornene used in the similar reaction in the prior art, the catalyst norbornene derivative used in the reaction related to the preparation method has the advantages that the using amount is greatly reduced, and the preparation cost is reduced.

3. The catalyst used in the reaction related to the preparation method of the invention is cheap metal palladium and phosphorus ligand, and is an important supplement compared with other catalysts or complexes

4. The preparation method has good substrate application range and functional group compatibility;

5. the invention provides a preparation method of flavonoid and isoflavone compounds, which can be used for preparing a large amount of flavonoid compounds, is suitable for industrial production and has great application potential.

6. The invention also provides application of the prepared flavonoid and isoflavone compound in preparation of the umbralisib core skeleton.

Detailed Description

The scheme of the invention will be explained with reference to the examples. It will be appreciated by those skilled in the art that the following examples are illustrative of the invention only and should not be taken as limiting the scope of the invention. The examples, where specific techniques or conditions are not indicated, are to be construed according to the techniques or conditions described in the literature in the art or according to the product specifications. The methods used are conventional methods known in the art unless otherwise specified, and the consumables and reagents used are commercially available unless otherwise specified. Unless otherwise defined, technical and scientific terms used herein have the same meaning as is familiar to those skilled in the art. In addition, any methods or materials similar or equivalent to those described herein can also be used in the present invention.

Example 1:

to a reaction tube dried and equipped with a magnetic stirrer, under argon, was added palladium acetate (1.2mg,0.005mmol), triphenylphosphine (1.4mg,0.005mmol), potassium carbonate (13.8mg,0.1mmol) and 3-iodochromone (27.2mg,0.1mmol), followed by dried 1, 4-epoxyhexaalkane (1mL) dissolved with 1-ethyl formate-2-norbornene (8.3mg,0.05 mmol). To the solution were added methyl o-bromobenzoate (21.5mg,0.1mmol) and styrene (12.5mg,0.12mmol) again. The mixture was reacted at 100 ℃ under an argon atmosphere for 18 hours. After the reaction, the reaction mixture was cooled to room temperature, filtered through celite, washed with ethyl acetate, and then the solvent was removed by distillation under reduced pressure, and the compound 1 was isolated and purified by column chromatography (yellow oily liquid, 90% yield).

Examples 2 to 40 are as follows:

example 41:

to a dry reaction tube equipped with a magnetic stirrer, under argon, was added palladium acetate (1.2mg,0.005mmol), triphenylphosphine (1.4mg,0.005mmol), potassium carbonate (13.8mg,0.1mmol), 3-iodochromone (27.2mg,0.1mmol) and potassium phenyltrifluoroborate (27.6mg,0.15mmol) followed by dry tetrahydrofuran (1mL) dissolved with 1-ethyl formate-2-norbornene (8.3mg,0.05 mmol). To the above solution was then added o-bromobenzoate methyl ester (21.5mg,0.1 mmol). The mixture was reacted at 120 ℃ under an argon atmosphere for 36 hours. After completion of the reaction, it was cooled to room temperature, and the mixture was filtered through celite, washed with ethyl acetate, and the solvent was removed by distillation under the reduced pressure, followed by column chromatography to isolate and purify compound 41 (colorless oily liquid, 64% yield).

Examples 42 to 54 are as follows:

example 55:

to a dry reaction tube equipped with a magnetic stirrer, under argon, was added palladium acetate (1.2mg,0.005mmol), triphenylphosphine (1.4mg,0.005mmol), potassium carbonate (13.8mg,0.1mmol), 3-iodochromone (27.2mg,0.1mmol) and potassium phenyltrifluoroborate (27.6mg,0.15mmol), followed by dry tetrahydrofuran (1mL) dissolved with 1-ethyl formate-2-norbornene (8.3mg,0.05mmol) and iodomethane (14.2mg,0.1 mmol). The mixture was reacted at 100 ℃ under an argon atmosphere for 36 hours. After completion of the reaction, it was cooled to room temperature, and the mixture was filtered through celite, washed with ethyl acetate, and the solvent was removed by distillation under the reduced pressure, followed by column chromatography to isolate and purify compound 55 (colorless oily liquid, 41% yield).

Examples 56 to 66 are as follows:

example 67:

to a dry reaction tube equipped with a magnetic stirrer, under argon, was added compound 66(11.0mg,0.044mmol) and 1mL of CCl₄And the temperature is increased to 80 ℃, and Br dissolved in the solution is gradually dropped₂(6.8. mu.L, 0.132mmol) of CCl₄(0.5mL) and reacted under exclusion of light. The reaction was monitored by GC, after completion of the reaction, cooled to room temperature, quenched with sodium thiosulfate solution, the organic was extracted with dichloromethane (3 × 5mL), the organic phase was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the crude product was directly purified by column chromatography to give compound 67 (colorless oily liquid, 99% yield).

The product obtained in example 1 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.34(dd,J＝7.9,1.7Hz,1H),8.16(dd,J＝7.4,1.8Hz,1H),7.91(d,J＝16.2Hz,1H),7.71–7.62(m,3H),7.57(dd,J＝7.1,1.8Hz,1H),7.45–7.41(m,1H),7.39(d,J＝8.4Hz,1H),7.29–7.22(m,4H),7.19–7.15(m,1H),6.59(d,J＝16.3Hz,1H),3.69(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.53,166.37,163.84,155.57,138.21,134.16,133.90,133.61,132.42,131.35,131.08,130.64,130.58,128.57,127.62,126.54,126.40,125.22,123.88,119.83,118.10,117.81,52.70；HRMS(ESI-TOF):calc’d for C₂₅H₁₉O₄ ⁺[M+H⁺]383.1278,found383.1269.

the product obtained in example 2 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.64–8.62(m,1H),8.09(dd,J＝7.8,1.3Hz,1H),7.66(td,J＝7.5,1.5Hz,1H),7.61–7.54(m,4H),7.48(d,J＝16.3Hz,1H),7.46(dd,J＝7.6,1.3Hz,1H),7.25–7.14(m,5H),6.71(d,J＝16.4Hz,1H),3.71(s,3H)；¹³C NMR(100MHz,CDCl₃):δ179.75,166.34,150.13,138.18,137.27,136.69,134.29,132.59,131.72,131.34,131.09,131.04,130.56,129.94,129.86,129.63,128.55,127.67,126.70,125.65,122.23,52.58；HRMS(ESI-TOF):calc’d for C₂₅H₁₈NaO₃S⁺[M+Na⁺]421.0869,found421.0879.

the product obtained in example 3 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.14(dd,J＝7.4,1.8Hz,1H),7.94(d,J＝16.2Hz,1H),7.69–7.61(m,2H),7.57(d,J＝7.1Hz,1H),7.53(t,J＝8.3Hz,1H),7.26–7.21(m,4H),7.18–7.14(m,1H),6.94(d,J＝8.4Hz,1H),6.84(d,J＝8.3Hz,1H),6.57(d,J＝16.2Hz,1H),4.04(s,3H),3.69(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.40,166.56,161.71,160.31,157.58,138.49,133.86,133.65,133.60,132.30,131.45,131.04,130.85,130.48,128.54,127.45,126.50,119.77,118.95,114.47,109.83,106.40,56.57,52.70；HRMS(ESI-TOF):calc’d for C₂₆H₂₀NaO₅ ⁺[M+Na⁺]435.1203,found435.1201.

the product obtained in example 4 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.15(dd,J＝7.7,1.5Hz,1H),8.12(d,J＝1.0Hz,1H),7.88(d,J＝16.3Hz,1H),7.70–7.62(m,2H),7.56(dd,J＝7.4,1.6Hz,1H),7.46(dd,J＝8.5,2.2Hz,1H),7.30–7.22(m,5H),7.19–7.15(m,1H),6.60(d,J＝16.2Hz,1H),3.68(s,3H),2.49(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.59,166.46,163.68,153.90,138.28,135.14,134.89,134.01,132.37,131.36,131.07,130.72,130.51,128.56,127.57,126.55,125.68,123.55,120.01,117.95,117.58,52.70,21.19；HRMS(ESI-TOF):calc’d for C₂₆H₂₀NaO₄ ⁺[M+Na⁺]419.1254,found419.1244.

the product obtained in example 5 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.18(dd,J＝7.4,1.8Hz,1H),7.97(dd,J＝8.3,2.7Hz,1H),7.90(d,J＝16.2Hz,1H),7.72–7.64(m,2H),7.56(dd,J＝7.1,1.8Hz,1H),7.42–7.35(m,2H),7.28–7.22(m,4H),7.20–7.16(m,1H),6.55(d,J＝16.2Hz,1H),3.71(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.74(d,J＝2.4Hz),165.18(d,J＝209.7Hz),159.73(d,J＝246.0Hz),151.83,138.08,134.44,133.76,132.52,131.31,131.15,130.72,130.54,128.60,127.74,126.58,125.01(d,J＝7.3Hz),121.88(d,J＝25.9Hz),119.97(d,J＝8.0Hz),119.51,117.56,111.16(d,J＝23.9Hz),52.73；¹⁹F NMR(376MHz,CDCl₃):δ-115.40；HRMS(ESI-TOF):calc’d for C₂₅H₁₇FNaO₄ ⁺[M+Na⁺]423.1003,found423.0997.

the product obtained in example 6 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.29(d,J＝2.6Hz,1H),8.19–8.17(m,1H),7.88(d,J＝16.3Hz,1H),7.70–7.66(m,2H),7.60–7.55(m,2H),7.35(d,J＝8.9Hz,1H),7.28–7.22(m,4H),7.20–7.16(m,1H),6.55(d,J＝16.3Hz,1H),3.71(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.31,166.15,164.04,153.88,138.00,134.55,133.80,133.65,132.53,131.28,131.15,131.10,130.74,130.50,128.58,127.76,126.58,125.77,124.79,119.60,119.42,118.19,52.72；HRMS(ESI-TOF):calc’d for C₂₅H₁₇ClNaO₄ ⁺[M+Na⁺]439.0708,found439.0706.

the product obtained in example 7 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.45(d,J＝2.4Hz,1H),8.17(dd,J＝7.6,1.6Hz,1H),7.87(d,J＝16.2Hz,1H),7.72(dd,J＝8.8,2.5Hz,1H),7.66(qd,J＝7.4,1.7Hz,2H),7.56(dd,J＝7.3,1.6Hz,1H),7.29(d,J＝8.9Hz,1H),7.25–7.21(m,4H),7.20–7.16(m,1H),6.54(d,J＝16.3Hz,1H),3.71(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.16,166.15,164.02,154.31,137.99,136.53,134.58,133.64,132.53,131.28,131.16,130.75,130.49,128.99,128.59,127.77,126.59,125.17,119.83,119.41,118.58,118.30,52.73；HRMS(ESI-TOF):calc’d for C₂₅H₁₇BrNaO₄ ⁺[M+Na⁺]483.0202,found483.0198.

the product obtained in example 8 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.15(dd,J＝7.7,1.5Hz,1H),7.92(d,J＝16.3Hz,1H),7.71(d,J＝3.1Hz,1H),7.69–7.62(m,2H),7.56(dd,J＝7.3,1.6Hz,1H),7.34(d,J＝9.1Hz,1H),7.29–7.22(m,5H),7.19–7.15(m,1H),6.59(d,J＝16.2Hz,1H),3.93(s,3H),3.69(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.34,166.42,163.70,157.11,150.51,138.30,134.03,133.98,132.39,131.37,131.09,130.72,130.55,128.60,127.60,126.55,124.46,123.79,120.00,119.29,117.37,105.41,56.07,52.72；HRMS(ESI-TOF):calc’d for C₂₆H₂₀NaO₅ ⁺[M+Na⁺]435.1203,found435.1196.

the product obtained in example 9 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.22(d,J＝8.1Hz,1H),8.16(dd,J＝7.4,1.7Hz,1H),7.91(d,J＝16.3Hz,1H),7.70–7.62(m,2H),7.56(dd,J＝7.2,1.8Hz,1H),7.29–7.22(m,5H),7.19–7.15(m,2H),6.59(d,J＝16.3Hz,1H),3.70(s,3H),2.48(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.44,166.40,163.54,155.69,144.91,138.27,133.99,132.37,131.36,131.04,130.65,130.48,128.54,127.54,126.78,126.51,126.14,121.64,119.97,117.94,117.48,52.68,21.92；HRMS(ESI-TOF):calc’d for C₂₆H₂₀NaO₄ ⁺[M+Na⁺]419.1254,found419.1249.

the product obtained in example 10 was characterized as follows:

¹HNMR(400MHz,CDCl₃):δ8.36(dd,J＝8.9,6.3Hz,1H),8.18(dd,J＝7.7,1.4Hz,1H),7.88(dd,J＝16.2,1.0Hz,1H),7.72–7.64(m,2H),7.56(dd,J＝7.4,1.5Hz,1H),7.28–7.22(m,4H),7.20–7.14(m,2H),7.07(dd,J＝8.9,2.4Hz,1H),6.56(dd,J＝16.3,0.9Hz,1H),3.73(s,3H)；¹³CNMR(100MHz,CDCl₃):δ176.64,166.15,165.65(d,J＝254.7Hz),163.99,156.45(d,J＝13.2Hz),138.05,134.51,133.63,132.53,131.32,131.14,130.70,130.47,128.99(d,J＝10.5Hz),128.57,127.72,126.55,120.75(d,J＝2.2Hz),119.46,118.20,114.05(d,J＝22.6Hz),104.37(d,J＝25.3Hz),52.71；¹⁹F NMR(376MHz,CDCl₃):δ-103.29；HRMS(ESI-TOF):calc’d for C₂₅H₁₇FNaO₄ ⁺[M+Na⁺]423.1003,found423.1001.

the product obtained in example 11 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.28(d,J＝8.4Hz,1H),8.18(dd,J＝7.6,1.6Hz,1H),7.88(d,J＝16.3Hz,1H),7.72–7.66(m,2H),7.56(dd,J＝7.4,1.6Hz,1H),7.42(d,J＝1.7Hz,1H),7.40(dd,J＝8.4,1.9Hz,1H),7.28–7.22(m,4H),7.20–7.16(m,1H),6.55(d,J＝16.3Hz,1H),3.74(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.74,166.12,163.92,155.62,139.59,138.03,134.57,133.63,132.55,131.32,131.17,130.74,130.45,128.59,127.85,127.76,126.58,126.08,122.41,119.44,118.41,117.86,52.75；HRMS(ESI-TOF):calc’d for C₂₅H₁₇ClNaO₄ ⁺[M+Na⁺]439.0708,found439.0707.

the product obtained in example 12 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.19(d,J＝8.4Hz,1H),8.21–8.14(m,1H),7.88(d,J＝16.2Hz,1H),7.71–7.63(m,2H),7.59(d,J＝1.8Hz,1H),7.56(t,J＝2.0Hz,1H),7.54–7.53(m,1H),7.27–7.22(m,4H),7.20–7.15(m,1H),6.54(d,J＝16.2Hz,1H),3.73(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.85,166.12,163.88,155.58,138.03,134.58,133.64,132.57,131.32,131.18,130.75,130.45,128.85,128.60,127.89,127.81,127.77,126.59,122.77,120.93,119.45,118.45,52.77；HRMS(ESI-TOF):calc’d for C₂₅H₁₇BrNaO₄ ⁺[M+Na⁺]483.0202,found483.0199.

the product obtained in example 13 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.24(d,J＝8.9Hz,1H),8.16(dd,J＝7.6,1.7Hz,1H),7.89(d,J＝16.3Hz,1H),7.71–7.62(m,2H),7.56(dd,J＝7.2,1.7Hz,1H),7.28–7.22(m,4H),7.19–7.15(m,1H),7.01(dd,J＝8.9,2.3Hz,1H),6.79(d,J＝2.3Hz,1H),6.58(d,J＝16.2Hz,1H),3.88(s,3H),3.71(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.99,166.48,164.15,163.32,157.29,138.31,134.10,133.98,132.43,131.41,131.10,130.68,130.51,128.57,127.85,127.57,126.55,119.95,117.94,117.84,114.79,99.81,55.93,52.73；HRMS(ESI-TOF):calc’d for C₂₆H₂₀NaO₅ ⁺[M+Na⁺]435.1203,found435.1195.

the product obtained in example 14 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.18(dd,J＝7.3,1.8Hz,1H),7.88(d,J＝16.3Hz,1H),7.77(ddd,J＝8.2,3.0,1.8Hz,1H),7.69(td,J＝7.3,1.7Hz,2H),7.57(dd,J＝6.9,1.9Hz,1H),7.28–7.24(m,4H),7.24–7.17(m,2H),6.54(d,J＝16.3Hz,1H),3.76(s,3H)；¹³C NMR(100MHz,CDCl₃):δ175.68,166.04,163.82,158.42(dd,J＝248.6,9.5Hz),151.41(dd,J＝257.4,11.7Hz),141.26(d,J＝10.8Hz),137.88,135.01,133.29,132.57,131.45,131.20,130.93,130.59,128.63,127.91,126.63,126.06(d,J＝8.1Hz),119.13,118.09,108.92(dd,J＝28.8,20.1Hz),106.44(dd,J＝23.4,4.4Hz),53.14(d,J＝84.3Hz)；¹⁹F NMR(376MHz,CDCl₃):δ-112.27,-128.79；HRMS(ESI-TOF):calc’d for C₂₅H₁₆F₂NaO₄ ⁺[M+Na⁺]441.0909,found441.0906.

the product obtained in example 15 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ10.17(d,J＝8.6Hz,1H),8.16(d,J＝6.9Hz,1H),8.04(d,J＝9.0Hz,1H),7.90(d,J＝8.0Hz,1H),7.82(d,J＝16.4Hz,1H),7.77(d,J＝8.0Hz,1H),7.69–7.60(m,4H),7.42(d,J＝9.0Hz,1H),7.31(d,J＝7.6Hz,2H),7.26(t,J＝7.2Hz,2H),7.19(d,J＝7.1Hz,1H),6.76(d,J＝16.3Hz,1H),3.67(s,3H)；¹³C NMR(100MHz,CDCl₃):δ179.26,166.53,161.20,156.69,138.20,135.52,134.48,133.61,132.40,131.55,131.08,130.93,130.87,130.84,130.53,129.35,128.58,128.43,127.65,127.27,126.61,120.41,119.99,117.44,116.86,52.69；HRMS(ESI-TOF):calc’d for C₂₉H₂₀NaO₄ ⁺[M+Na⁺]455.1254,found455.1247.

the product obtained in example 16 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.23(dd,J＝5.5,2.2Hz,1H),8.21(dd,J＝4.3,1.9Hz,1H),7.86(d,J＝16.2Hz,1H),7.70–7.62(m,2H),7.58(ddd,J＝8.6,7.1,1.7Hz,1H),7.53(dd,J＝6.9,1.9Hz,1H),7.38(t,J＝7.5Hz,1H),7.28–7.22(m,5H),7.20–7.14(m,2H),7.10(t,J＝7.3Hz,2H),7.07–7.03(m,2H),6.57(d,J＝16.2Hz,1H),5.11(s,2H)；¹³C NMR(100MHz,CDCl₃):δ177.30,165.83,163.64,155.39,138.22,134.68,134.13,133.91,133.43,132.54,131.32,130.57,128.58,128.49,128.46,127.63,126.57,126.39,125.00,123.79,119.81,118.12,117.75,67.77；HRMS(ESI-TOF):calc’d for C₃₁H₂₂NaO₄ ⁺[M+Na⁺]481.1410,found481.1402.

the product obtained in example 17 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.30(dd,J＝8.0,1.6Hz,1H),8.01(d,J＝16.2Hz,1H),7.66–7.63(m,2H),7.60–7.50(m,3H),7.42(t,J＝7.4Hz,1H),7.38–7.34(m,3H),7.27(t,J＝7.5Hz,2H),7.20(t,J＝7.1Hz,1H),6.75(d,J＝16.2Hz,1H),2.94(s,3H),2.90(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.41,169.83,162.13,155.41,138.16,137.42,134.79,133.69,131.54,131.10,130.65,129.02,128.62,127.79,127.70,126.63,126.42,125.31,123.75,119.65,118.50,117.66,39.24,35.10；HRMS(ESI-TOF):calc’d for C₂₆H₂₁NNaO₃ ⁺[M+Na⁺]418.1414,found481.1409.

the product obtained in example 18 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.31(d,J＝7.1Hz,1H),8.01(d,J＝16.3Hz,1H),7.69–7.62(m,3H),7.61–7.54(m,2H),7.44–7.41(m,2H),7.36–7.35(m,2H),7.30–7.26(m,2H),7.22–7.18(m,1H),6.76(d,J＝16.3Hz,1H),3.46(s,3H),3.15(s,3H)；¹³C NMR(150MHz,CDCl₃):δ177.58,169.70,162.50,155.39,138.27,135.65,134.66,133.67,131.62,131.31,130.44,129.61,128.63,128.57,127.67,126.65,126.43,125.32,123.75,119.96,118.25,117.73,61.39,32.86；HRMS(ESI-TOF):calc’d for C₂₆H₂₁NNaO₄ ⁺[M+Na⁺]434.1363,found434.1357.

the product obtained in example 19 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.35(dd,J＝8.0,1.7Hz,1H),8.29–8.27(m,1H),7.86(d,J＝16.3Hz,1H),7.82–7.78(m,2H),7.69(ddd,J＝8.6,7.2,1.7Hz,1H),7.65–7.63(m,1H),7.46(t,J＝7.8Hz,1H),7.39(d,J＝8.4Hz,1H),7.25–7.22(m,4H),7.21–7.18(m,1H),6.50(d,J＝16.3Hz,1H),3.16(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.29,160.93,155.37,139.98,137.81,135.22,134.08,133.98,132.61,132.57,131.55,130.68,128.68,127.98,126.70,126.59,125.60,123.99,119.28,117.52,45.07；HRMS(ESI-TOF):calc’d for C₂₄H₁₈NaO₄S⁺[M+Na⁺]425.0818,found425.0814.

the product obtained in example 20 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.33(dd,J＝8.0,1.7Hz,1H),8.29(dd,J＝8.0,1.5Hz,1H),7.83–7.73(m,3H),7.67(td,J＝7.1,1.7Hz,2H),7.45(t,J＝7.5Hz,1H),7.37(d,J＝8.4Hz,1H),7.30–7.24(m,4H),7.22–7.18(m,1H),6.61(d,J＝16.2Hz,1H)；¹³C NMR(100MHz,CDCl₃):δ177.31,159.87,155.61,148.02,137.78,135.46,133.90,133.83,132.67,131.65,128.64,128.39,127.97,126.65,126.39,125.53,125.42,123.76,118.90,118.87,117.89；HRMS(ESI-TOF):calc’d for C₂₃H₁₅NNaO₄ ⁺[M+Na⁺]392.0893,found392.0887.

the product obtained in example 21 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.32(dd,J＝8.0,1.6Hz,1H),7.87(d,J＝16.1Hz,1H),7.76(d,J＝2.6Hz,1H),7.66(ddd,J＝8.5,7.1,1.7Hz,1H),7.56(d,J＝8.4Hz,1H),7.44(t,J＝7.6Hz,1H),7.35(d,J＝8.5Hz,1H),7.33–7.26(m,5H),7.23–7.19(m,1H),6.63(d,J＝16.1Hz,1H),3.99(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.44,161.64,160.13,155.60,149.13,137.96,135.14,133.80,133.77,128.64,127.89,126.67,126.37,125.42,123.78,120.36,119.50,119.25,118.82,117.87,110.60,56.36；HRMS(ESI-TOF):calc’d for C₂₄H₁₇NNaO₅ ⁺[M+Na⁺]422.0999,found422.0994.

the product obtained in example 22 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.32(dd,J＝8.0,1.7Hz,1H),8.09(d,J＝8.4Hz,1H),7.89(d,J＝16.2Hz,1H),7.64(ddd,J＝8.6,7.1,1.7Hz,1H),7.60(dd,J＝8.5,2.2Hz,1H),7.55(d,J＝2.2Hz,1H),7.42(t,J＝7.6Hz,1H),7.37(d,J＝8.4Hz,1H),7.28–7.22(m,4H),7.20–7.16(m,1H),6.50(d,J＝16.2Hz,1H),3.67(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.32,165.43,161.97,155.54,138.90,138.01,135.54,134.83,133.77,132.51,131.21,130.73,128.98,128.64,127.83,126.63,126.46,125.38,123.85,119.20,118.39,117.82,52.86；HRMS(ESI-TOF):calc’d for C₂₅H₁₇ClNaO₄ ⁺[M+Na⁺]439.0708,found439.0701.

the product obtained in example 23 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.34(dd,J＝8.0,1.7Hz,1H),7.97(d,J＝4.2Hz,1H),7.95(d,J＝10.5Hz,1H),7.64(ddd,J＝8.6,7.0,1.7Hz,1H),7.49–7.47(m,1H),7.46–7.40(m,2H),7.38(d,J＝8.4Hz,1H),7.31–7.23(m,4H),7.20–7.15(m,1H),6.61(d,J＝16.3Hz,1H),3.67(s,3H),2.51(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.56,166.65,164.09,155.56,141.03,138.32,133.99,133.53,132.98,131.64,131.32,131.05,130.59,128.56,127.56,126.57,126.39,125.16,123.89,120.07,118.07,117.79,52.65,21.49；HRMS(ESI-TOF):calc’d for C₂₆H₂₀NaO₄ ⁺[M+Na⁺]419.1254,found419.1250.

the product obtained in example 24 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.33(dd,J＝8.0,1.6Hz,1H),7.96(d,J＝16.3Hz,1H),7.67–7.63(m,2H),7.49(d,J＝8.5Hz,1H),7.43(t,J＝7.6Hz,1H),7.39(d,J＝8.4Hz,1H),7.32–7.30(m,2H),7.28–7.24(m,2H),7.21–7.16(m,2H),6.63(d,J＝16.3Hz,1H),3.95(s,3H),3.68(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.62,166.47,163.89,161.01,155.56,138.35,133.96,133.53,132.94,132.38,128.59,127.57,126.58,126.40,126.03,125.15,123.89,120.17,118.13,117.99,117.77,116.00,55.90,52.80；HRMS(ESI-TOF):calc’d for C₂₆H₂₁O₅ ⁺[M+Na⁺]413.1384,found413.1378.

the product obtained in example 25 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.97(d,J＝2.4Hz,1H),8.51(dd,J＝8.4,2.4Hz,1H),8.34(d,J＝7.2Hz,1H),7.86–7.80(m,2H),7.71–7.67(m,1H),7.47(t,J＝7.6Hz,1H),7.39(d,J＝8.4Hz,1H),7.27–7.26(m,4H),7.24–7.19(m,1H),6.51(d,J＝16.2Hz,1H),3.79(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.11,164.39,160.51,155.57,148.74,139.55,137.58,135.78,134.01,132.95,132.58,128.71,128.14,126.85,126.62,126.52,126.15,125.60,123.77,118.86,118.58,117.77,53.38；HRMS(ESI-TOF):calc’d for C₂₅H₁₇NNaO₆ ⁺[M+Na⁺]450.0948,found450.0946.

the product obtained in example 26 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.32(dd,J＝8.0,1.7Hz,1H),7.89(d,J＝16.3Hz,1H),7.83(dd,J＝8.9,2.7Hz,1H),7.64(ddd,J＝8.6,7.1,1.7Hz,1H),7.55(dd,J＝8.5,5.3Hz,1H),7.42(ddd,J＝8.1,7.1,1.1Hz,1H),7.39–7.34(m,2H),7.28–7.22(m,4H),7.20–7.15(m,1H),6.53(d,J＝16.2Hz,1H),3.69(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.34,165.11(d,J＝2.8Hz),163.23(d,J＝252.9Hz),162.47,155.46,137.96,134.45,133.61,133.42(d,J＝8.4Hz),132.95(d,J＝7.6Hz),129.96(d,J＝3.7Hz),128.53,127.68,126.46,126.35,125.22,123.75,119.60,119.40(d,J＝3.7Hz),118.36(d,J＝3.2Hz),118.14,117.67,52.91；¹⁹F NMR(376MHz,CDCl₃):δ-108.10；HRMS(ESI-TOF):calc’d for C₂₅H₁₇FNaO₄ ⁺[M+Na⁺]423.1003,found423.0995.

the product obtained in example 27 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.31(dd,J＝8.0,1.7Hz,1H),8.19(dd,J＝7.4,1.8Hz,1H),7.73–7.65(m,3H),7.49–7.38(m,4H),7.17(d,J＝15.8Hz,1H),3.72(s,3H),3.69(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.92,168.33,168.11,165.86,155.45,135.94,134.05,133.05,132.71,131.40,131.23,131.11,130.14,126.49,125.73,123.85,122.54,117.87,116.07,52.71,51.61；HRMS(ESI-TOF):calc’d for C₂₁H₁₆NaO₆ ⁺[M+Na⁺]387.0839,found387.0835.

the product obtained in example 28 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.31(dd,J＝8.0,1.6Hz,1H),8.17(dd,J＝7.7,1.5Hz,1H),7.73–7.63(m,3H),7.49(d,J＝8.7Hz,1H),7.45(t,J＝7.5Hz,1H),7.40(d,J＝9.5Hz,1H),7.37(d,J＝2.1Hz,1H),7.07(d,J＝15.7Hz,1H),3.71(s,3H),1.43(s,9H)；¹³C NMR(100MHz,CDCl₃):δ177.02,167.85,167.21,165.88,155.44,134.53,133.97,133.11,132.69,131.35,131.23,131.01,130.14,126.49,125.65,124.92,123.91,117.85,116.18,80.14,52.69,28.25；HRMS(ESI-TOF):calc’d for C₂₄H₂₂NaO₆ ⁺[M+Na⁺]429.1309,found429.1305.

the product obtained in example 29 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.31(dd,J＝8.0,1.7Hz,1H),8.17(dd,J＝7.6,1.5Hz,1H),8.14(d,J＝15.1Hz,1H),7.71–7.62(m,3H),7.50(dd,J＝7.3,1.4Hz,1H),7.45(ddd,J＝8.1,7.2,1.1Hz,1H),7.39(dd,J＝8.4,1.1Hz,1H),7.13(d,J＝15.1Hz,1H),3.70(s,3H),3.17(s,3H),2.98(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.57,167.93,167.48,165.92,155.46,133.93,133.32,133.27,132.77,131.39,130.94,130.02,126.31,125.61,123.97,122.05,117.94,116.47,52.63,37.47,35.85；HRMS(ESI-TOF):calc’d for C₂₂H₁₉NNaO₅ ⁺[M+Na⁺]400.1155,found400.1151.

the product obtained in example 30 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.29(dd,J＝8.0,1.7Hz,1H),8.17(dd,J＝7.6,1.6Hz,1H),7.71–7.62(m,3H),7.48–7.33(m,4H),6.93(dd,J＝25.0,17.3Hz,1H),4.00(p,J＝7.2Hz,4H),3.71(s,3H),1.24(t,J＝7.0Hz,6H)；¹³C NMR(100MHz,CDCl₃):δ177.16,167.91,165.82,155.46,139.54(d,J＝8.1Hz),134.07,132.98,132.74,131.43,131.20,131.11,130.17,126.38,125.73,124.02,119.67(d,J＝184.4Hz),117.91,116.05(d,J＝21.6Hz),61.77(d,J＝5.3Hz),52.71,16.42(d,J＝6.5Hz)；³¹P NMR(162MHz,CDCl₃)δ19.35；HRMS(ESI-TOF):calc’d for C₂₃H₂₃NaO₇P⁺[M+Na⁺]465.1074,found465.1070.

the product obtained in example 31 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.23(ddd,J＝9.1,7.6,1.7Hz,2H),8.15(d,J＝15.0Hz,1H),7.84(d,J＝7.2Hz,2H),7.79–7.71(m,2H),7.71–7.65(m,1H),7.57(t,J＝7.3Hz,1H),7.53–7.46(m,3H),7.47–7.43(m,1H),7.40(d,J＝8.4Hz,1H),7.11(d,J＝15.0Hz,1H),3.74(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.63,169.54,165.77,155.46,140.91,134.40,133.27,133.04,132.87,132.37,131.58,131.51,131.22,130.23,129.30,127.76,126.37,126.08,123.66,117.99,114.61,52.83；HRMS(ESI-TOF):calc’d for C₂₅H₁₈NaO₆S⁺[M+Na⁺]469.0716,found469.0713.

the product obtained in example 32 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.28(dd,J＝8.0,1.7Hz,1H),8.05–8.03(m,1H),7.70–7.66(m,1H),7.62–7.55(m,2H),7.46–7.39(m,3H),7.27(s,1H),3.75(s,3H),3.71(s,3H),1.59(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.47,167.95,166.69,163.07,156.19,134.05,133.61,133.37,132.20,130.98,130.77,130.73,130.54,130.39,126.43,125.49,123.25,118.42,117.88,52.72,52.07,14.81；HRMS(ESI-TOF):calc’d for C₂₂H₁₈NaO₆ ⁺[M+Na⁺]401.0996,found401.1002.

the product obtained in example 33 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.29(dd,J＝7.9,1.7Hz,1H),8.10(dd,J＝7.7,1.4Hz,1H),7.66–7.59(m,3H),7.51(dd,J＝7.2,1.6Hz,1H),7.43–7.41(m,1H),7.38(d,J＝8.5Hz,1H),6.76(d,J＝19.4Hz,1H),6.44(d,J＝19.3Hz,1H),3.70(s,3H),-0.04(s,9H)；¹³C NMR(100MHz,CDCl₃):δ177.61,166.51,163.68,155.72,137.96,134.29,134.02,133.56,132.13,131.20,130.86,130.82,130.33,126.37,125.16,124.13,119.57,117.84,52.70,-1.52；HRMS(ESI-TOF):calc’d for C₂₂H₂₂NaO₄Si⁺[M+Na⁺]401.1180,found401.1179.

the product obtained in example 34 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.31(dd,J＝8.0,1.7Hz,1H),8.13(dd,J＝7.8,1.4Hz,1H),7.69–7.60(m,3H),7.51(dd,J＝7.7,1.2Hz,1H),7.42(ddd,J＝8.1,7.2,1.1Hz,1H),7.38(dd,J＝8.4,1.0Hz,1H),6.29–6.16(m,2H),5.32(dd,J＝10.8,3.2Hz,1H),3.71(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.58,166.33,163.84,155.69,133.94,133.61,132.46,131.18,131.06,130.46,130.42,127.81,126.40,125.20,124.01,120.86,118.27,117.83,52.71；HRMS(ESI-TOF):calc’d for C₁₉H₁₄NaO₄ ⁺[M+Na⁺]329.0784,found329.0784.

the product obtained in example 35 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.23(dd,J＝8.0,1.7Hz,1H),8.06(dd,J＝7.4,1.7Hz,1H),7.64–7.56(m,3H),7.44(dd,J＝7.2,1.7Hz,1H),7.38–7.34(m,2H),7.30(dd,J＝8.4,1.0Hz,1H),3.61(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.43,166.27,163.72,155.53,134.15,133.39,132.39,131.49,131.07,130.16,126.46,125.98,124.96,123.88,118.88,117.68,52.53；HRMS(ESI-TOF):calc’d for C₁₇H₁₂NaO₄ ⁺[M+Na⁺]303.0628,found303.0620.

the product obtained in example 36 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.38(d,J＝7.9Hz,1H),8.19(dd,J＝7.2,1.8Hz,1H),8.07(d,J＝16.3Hz,1H),7.79–7.73(m,2H),7.71–7.65(m,5H),7.61(dd,J＝7.1,1.8Hz,1H),7.47–7.38(m,5H),6.74(d,J＝16.2Hz,1H),3.71(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.55,166.43,163.84,155.60,135.66,134.26,133.94,133.71,133.63,133.09,132.45,131.41,131.12,130.75,130.63,128.18,128.14,127.71,126.95,126.45,126.28,125.93,125.25,123.90,123.32,120.19,118.22,117.83,52.73；HRMS(ESI-TOF):calc’d for C₂₉H₂₀NaO₄ ⁺[M+Na⁺]455.1254,found455.1251.

the product obtained in example 37 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.35(dd,J＝8.0,1.7Hz,1H),8.20(dd,J＝7.4,1.8Hz,1H),7.99–7.93(m,2H),7.74–7.65(m,5H),7.60(dd,J＝7.1,1.7Hz,1H),7.51(s,1H),7.45(t,J＝7.5Hz,1H),7.43–7.36(m,2H),7.27–7.25(m,1H),7.18(d,J＝8.1Hz,2H),7.13(t,J＝7.6Hz,1H),6.65(d,J＝16.4Hz,1H),3.70(s,3H),2.32(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.59,166.27,163.83,155.60,145.11,135.66,135.11,133.97,133.67,132.59,131.30,131.24,130.70,130.55,130.00,129.16,126.95,126.40,125.29,124.93,124.12,123.90,123.50,121.83,121.12,120.47,118.06,117.88,113.87,52.73,21.67；HRMS(ESI-TOF):calc’d for C₃₄H₂₅NNaO₆S⁺[M+Na⁺]598.1295,found598.1293.

the product obtained in example 38 was characterized as follows:

¹H NMR(400MHz,Methanol-d₄):δ8.22(dd,J＝8.2,1.7Hz,1H),8.12(dd,J＝7.8,1.3Hz,1H),7.78–7.73(m,2H),7.68(td,J＝7.6,1.4Hz,1H),7.59(dd,J＝7.5,1.4Hz,1H),7.51–7.47(m,2H),6.56(d,J＝16.0Hz,1H),6.16(d,J＝16.1Hz,1H),3.71(s,3H),1.14(s,6H)；¹³C NMR(100MHz,CDCl₃):δ177.51,166.86,162.98,155.73,144.10,133.82,133.59,132.28,131.04,130.94,130.84,130.42,126.28,125.17,123.74,118.22,117.85,116.84,71.23,52.75,29.66；HRMS(ESI-TOF):calc’d for C₂₂H₂₀NaO₅ ⁺[M+Na⁺]387.1203,found387.1205.

the product obtained in example 39 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.29(dd,J＝8.1,1.7Hz,1H),7.70(d,J＝2.6Hz,1H),7.66(ddd,J＝8.6,7.1,1.7Hz,1H),7.53(d,J＝8.5Hz,1H),7.45–7.39(m,1H),7.36(d,J＝8.4Hz,1H),7.26(q,J＝4.3,3.5Hz,4H),7.05(d,J＝8.5Hz,1H),6.98(d,J＝15.9Hz,1H),6.65(dd,J＝8.4,2.7Hz,1H),6.58(d,J＝2.6Hz,1H),6.19(d,J＝15.9Hz,1H),5.91(s,1H),3.91(s,3H),2.82–2.71(m,2H),2.09(dd,J＝12.9,3.4Hz,1H),1.99–1.81(m,4H),1.71–1.65(m,2H),1.46–1.33(m,5H),1.27–1.20(m,1H),1.13(td,J＝12.6,4.1Hz,1H),0.87(s,3H)；¹³C NMR(100MHz,CDCl₃):δ178.00,161.58,159.74,155.84,153.86,149.16,142.79,138.27,133.98,133.47,132.50,126.47,126.29,125.51,123.57,120.54,119.71,119.30,117.97,116.87,115.37,112.74,110.29,84.50,56.32,49.57,47.43,43.41,39.44,37.32,32.52,29.76,27.44,26.30,23.50,14.24；HRMS(ESI-TOF):calc’d for C₃₆H₃₅NNaO₇ ⁺[M+Na⁺]616.2306,found616.2293.

the product obtained in example 40 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.28(dd,J＝8.0,1.7Hz,1H),8.09(dd,J＝7.7,1.5Hz,1H),7.74(dd,J＝7.5,1.5Hz,1H),7.65(qd,J＝8.2,7.7,1.7Hz,2H),7.59(td,J＝7.6,1.5Hz,1H),7.45–7.40(m,2H),3.72(s,3H),0.95(s,21H)；¹³C NMR(100MHz,CDCl₃):δ176.35,168.92,166.32,155.79,134.01,133.88,132.18,130.85,130.79,130.59,130.11,126.32,125.67,122.97,118.06,109.26,100.24,97.73,52.65,18.65,11.24；HRMS(ESI-TOF):calc’d for C₂₈H₃₂NaO₄Si⁺[M+Na⁺]483.1962,found483.1956.

the product obtained in example 41 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.33(dd,J＝8.3,1.7Hz,1H),7.95(dd,J＝7.6,1.5Hz,1H),7.68(ddd,J＝8.8,7.3,1.7Hz,1H),7.46–7.35(m,4H),7.23–7.16(m,6H),3.76(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.27,166.93,162.82,156.27,134.45,133.81,132.48,131.86,131.47,131.02,130.83,130.48,129.87,128.04,127.61,126.60,125.23,123.92,123.26,117.91,52.70；HRMS(ESI-TOF):calc’d for C₂₃H₁₆NaO₄ ⁺[M+Na⁺]379.0941,found379.0934.

the product obtained in example 42 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.10(s,1H),7.94(dd,J＝7.6,1.4Hz,1H),7.49(dd,J＝8.5,2.2Hz,1H),7.41(ddd,J＝14.9,7.4,1.5Hz,2H),7.37–7.31(m,2H),7.21–7.16(m,5H),3.75(s,3H),2.49(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.32,167.01,162.65,154.57,135.16,135.08,134.54,132.66,131.80,131.46,131.07,130.89,130.45,129.80,128.03,127.54,125.85,123.57,123.08,117.67,52.70,21.14；HRMS(ESI-TOF):calc’d for C₂₄H₁₈NaO₄ ⁺[M+Na⁺]393.1097,found393.1109.

the product obtained in example 43 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ7.97–7.94(m,2H),7.46–7.33(m,4H),7.26–7.16(m,6H),3.77(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.57(d,J＝2.4Hz),166.77,163.17,159.74(d,J＝246.6Hz),152.52,134.28,132.17,131.95,131.42,130.95,130.70,130.53,130.01,128.10,127.74,125.07(d,J＝7.3Hz),122.67,122.06(d,J＝25.5Hz),120.04(d,J＝8.2Hz),111.36(d,J＝23.6Hz),52.72；¹⁹F NMR(376MHz,CDCl₃):δ-115.47；HRMS(ESI-TOF):calc’d for C₂₃H₁₅FNaO₄ ⁺[M+Na⁺]397.0847,found397.0849.

the product obtained in example 44 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.28(dd,J＝8.0,1.7Hz,1H),7.66(ddd,J＝8.7,7.2,1.7Hz,1H),7.41(td,J＝7.5,1.1Hz,1H),7.39–7.26(m,6H),7.25–7.18(m,4H),3.01(s,3H),2.80(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.04,170.12,161.46,156.15,136.88,133.74,132.44,131.70,131.41,129.50,128.74,128.08,127.66,127.03,126.74,125.25,123.96,123.68,117.65,39.15,35.10；HRMS(ESI-TOF):calc’d for C₂₄H₁₉NNaO₃ ⁺[M+Na⁺]392.1257,found392.1260.

the product obtained in example 45 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.32(dd,J＝8.0,1.7Hz,1H),8.08(dd,J＝7.9,1.5Hz,1H),7.70(ddd,J＝8.6,7.2,1.7Hz,1H),7.56–7.47(m,2H),7.47–7.43(m,1H),7.40(d,J＝8.4Hz,1H),7.28(d,J＝1.7Hz,1H),7.23(s,5H)；¹³C NMR(100MHz,CDCl₃):δ177.06,159.40,156.28,148.22,134.11,133.28,132.68,131.83,130.95,130.85,129.00,128.36,128.09,126.59,125.58,124.91,123.90,118.05；HRMS(ESI-TOF):calc’d for C₂₁H₁₃NNaO₄ ⁺[M+Na⁺]366.0737,found366.0728.

the product obtained in example 46 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.32(dd,J＝7.9,1.7Hz,1H),7.97(dd,J＝7.6,1.5Hz,1H),7.69(ddd,J＝8.6,7.2,1.7Hz,1H),7.50–7.37(m,4H),7.22–7.11(m,2H),6.98–6.94(m,2H),6.92–6.84(m,1H),3.77(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.93,166.78,163.23,162.50(d,J＝245.5Hz),156.26,134.74(d,J＝8.7Hz),134.15,134.00,132.04,131.31,130.75,130.62,130.15,129.50(d,J＝8.6Hz),126.84(d,J＝3.1Hz),126.59,125.41,123.82,122.24,118.16,117.96,114.66(d,J＝21.1Hz),52.76；¹⁹F NMR(376MHz,CDCl₃):δ-113.72；HRMS(ESI-TOF):calc’d for C₂₃H₁₅FNaO₄ ⁺[M+Na⁺]397.0847,found397.0845.

the product obtained in example 47 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.32(dd,J＝8.2,1.6Hz,1H),7.95(dd,J＝7.3,1.7Hz,1H),7.69(td,J＝7.7,1.7Hz,1H),7.48–7.38(m,4H),7.21(dd,J＝7.2,1.7Hz,1H),7.15–7.06(m,3H),7.00(dt,J＝7.0,1.7Hz,1H),3.77(s,3H),2.30(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.07,166.86,163.00,156.25,138.01,134.38,133.89,133.20,132.00,131.38,130.79,130.49,129.99,129.21,128.37,127.97,126.59,126.33,125.31,123.88,122.85,117.94,52.74,16.03；HRMS(ESI-TOF):calc’d for C₂₄H₁₈NaO₄S⁺[M+Na⁺]425.0818,found425.0818.

the product obtained in example 48 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.33–8.30(m,1H),7.95(dd,J＝7.4,1.6Hz,1H),7.69–7.65(m,1H),7.45–7.36(m,4H),7.18(dd,J＝7.5,1.6Hz,1H),7.13(d,J＝8.7Hz,2H),6.75(d,J＝8.7Hz,2H),3.75(s,3H),3.75(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.55,167.03,162.55,158.97,156.26,134.67,133.73,132.19,131.91,131.50,130.84,130.48,129.76,126.60,125.15,124.62,123.87,122.81,117.88,113.63,55.27,52.69；HRMS(ESI-TOF):calc’d for C₂₄H₁₈NaO₅ ⁺[M+Na⁺]409.1046,found409.1042.

the product obtained in example 49 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.30(dd,J＝7.9,1.7Hz,1H),7.96(dd,J＝7.8,1.4Hz,1H),7.69(ddd,J＝8.7,7.2,1.7Hz,1H),7.62–7.59(m,2H),7.49–7.38(m,4H),7.25(d,J＝8.2Hz,2H),7.12(d,J＝8.7Hz,3H),6.81(d,J＝8.6Hz,2H),3.75(s,3H),2.43(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.92,166.67,163.14,156.23,148.95,145.35,134.18,134.02,132.34,132.28,131.92,131.59,131.36,130.83,130.52,130.01,129.79,128.64,126.49,125.43,123.74,122.06,122.00,117.96,52.74,21.84；HRMS(ESI-TOF):calc’d for C₃₀H₂₂NaO₇S⁺[M+Na⁺]549.0978,found549.0985.

the product obtained in example 50 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.33–8.31(m,1H),7.95(dd,J＝7.6,1.6Hz,1H),7.67(ddd,J＝8.8,7.5,1.8Hz,1H),7.47–7.35(m,4H),7.19(dd,J＝7.5,1.5Hz,1H),7.09(d,J＝8.1Hz,2H),7.01(d,J＝7.8Hz,2H),3.75(s,3H),2.26(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.42,166.99,162.55,156.25,137.25,134.59,133.72,131.87,131.48,130.81,130.45,129.77,129.35,128.83,126.60,125.14,123.89,123.18,117.87,52.68,21.39；HRMS(ESI-TOF):calc’d for C₂₄H₁₈NaO₄ ⁺[M+Na⁺]393.1097,found393.1096.

the product obtained in example 51 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.32(dd,J＝8.4,1.7Hz,1H),7.95–7.93(m,1H),7.66(ddd,J＝8.8,7.2,1.7Hz,1H),7.44–7.37(m,4H),7.21(dd,J＝6.8,2.2Hz,1H),7.01(d,J＝2.2Hz,1H),6.94(dd,J＝8.4,2.3Hz,1H),6.64(d,J＝8.4Hz,1H),3.75(s,6H),2.10(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.67,167.07,162.39,157.22,156.25,134.74,133.67,133.18,131.85,131.45,130.83,130.39,129.67,129.51,126.61,126.14,125.09,124.09,123.89,123.06,117.88,109.64,55.32,52.67,16.34；HRMS(ESI-TOF):calc’d for C₂₅H₂₀NaO₅ ⁺[M+Na⁺]423.1203,found423.1204.

the product obtained in example 52 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.31(dd,J＝8.0,1.7Hz,1H),8.00(dd,J＝7.5,1.7Hz,1H),7.92(d,J＝2.4Hz,1H),7.69(ddd,J＝8.7,7.2,1.7Hz,1H),7.53(dd,J＝8.5,2.4Hz,1H),7.49–7.41(m,4H),7.20(dd,J＝7.0,1.9Hz,1H),6.65(d,J＝8.5Hz,1H),3.85(s,3H),3.76(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.32,166.67,163.33,163.27,156.30,148.63,141.20,134.26,134.00,132.26,131.40,130.83,130.75,130.16,126.53,125.39,123.64,121.59,119.88,117.98,110.28,53.54,52.73；HRMS(ESI-TOF):calc’d for C₂₃H₁₇NNaO₅ ⁺[M+Na⁺]410.0999,found410.1001.

the product obtained in example 53 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.34(dd,J＝7.9,1.7Hz,1H),8.06–8.04(m,1H),7.68(ddd,J＝8.6,7.2,1.7Hz,1H),7.53–7.47(m,2H),7.48–7.39(m,2H),7.38–7.34(m,1H),7.28–7.26(m,1H),6.83(dd,J＝5.1,3.6Hz,1H),6.76(dd,J＝3.6,1.2Hz,1H),3.75(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.59,166.51,163.22,155.97,134.70,133.95,132.53,132.40,130.85,130.75,130.65,130.27,129.29,127.11,126.66,126.24,125.42,123.40,117.92,117.15,52.72；HRMS(ESI-TOF):calc’d for C₂₁H₁₄NaO₄S⁺[M+Na⁺]385.0505,found385.0497.

the product obtained in example 54 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.36(dd,J＝8.2,1.7Hz,1H),8.10(d,J＝1.7Hz,1H),8.03–7.97(m,1H),7.94(dd,J＝7.7,1.4Hz,1H),7.82–7.78(m,1H),7.71(ddd,J＝8.8,7.2,1.7Hz,1H),7.66(d,J＝8.3Hz,1H),7.49–7.44(m,2H),7.43–7.40(m,2H),7.37(dd,J＝7.6,1.5Hz,1H),7.32(td,J＝7.5,1.4Hz,1H),7.26–7.21(m,2H),3.80(s,3H)；¹³C NMR(100MHz,CDCl₃):δ177.42,166.99,163.10,156.31,139.70,138.88,135.59,135.51,134.41,133.91,132.01,131.49,130.85,130.48,129.96,129.56,128.80,126.77,126.62,125.33,124.43,124.30,123.90,123.02,122.87,122.46,121.73,117.96,52.76；HRMS(ESI-TOF):calc’d for C₂₉H₁₈NaO₄S⁺[M+Na⁺]485.0818,found485.0828.

the product obtained in example 55 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.24(dd,J＝7.9,1.7Hz,1H),7.66(ddd,J＝8.6,7.1,1.7Hz,1H),7.48–7.41(m,3H),7.41–7.34(m,2H),7.32–7.27(m,2H),2.33(s,3H)；¹³C NMR(100MHz,CDCl₃):δ176.93,163.45,156.06,133.48,133.27,130.57,128.55,127.92,126.45,124.96,123.81,123.66,117.78,19.70；HRMS(ESI-TOF):calc’d for C₁₆H₁₂NaO₂ ⁺[M+Na⁺]259.0730,found259.0727.

the product obtained in example 56 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.24(dd,J＝7.9,1.7Hz,1H),7.67(ddd,J＝8.7,7.1,1.7Hz,1H),7.48–7.35(m,5H),7.29–7.26(m,2H),2.60(q,J＝7.5Hz,2H),1.27(t,J＝7.6Hz,3H)；¹³C NMR(100MHz,CDCl₃):δ177.25,167.54,156.18,133.45,133.24,130.49,128.58,127.91,126.43,124.92,123.64,123.21,117.82,26.31,12.10；HRMS(ESI-TOF):calc’d for C₁₇H₁₄NaO₂ ⁺[M+Na⁺]273.0886,found273.0884.

the product obtained in example 57 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ7.86(dd,J＝8.3,3.1Hz,1H),7.50–7.41(m,3H),7.41–7.34(m,2H),7.28–7.25(m,2H),2.60(q,J＝7.5Hz,2H),1.26(t,J＝7.5Hz,3H)；¹³C NMR(100MHz,CDCl₃):δ176.47(d,J＝2.2Hz),167.86,159.51(d,J＝245.7Hz),152.37,132.87,130.40,128.62,128.03,124.72(d,J＝7.3Hz),122.60,121.65(d,J＝25.5Hz),119.89(d,J＝8.4Hz),111.11(d,J＝23.4Hz),26.27,12.03；¹⁹F NMR(376MHz,CDCl₃):δ-115.94；HRMS(ESI-TOF):calc’d for C₁₇H₁₃FNaO₂ ⁺[M+Na⁺]291.0792,found291.0795.

the product obtained in example 58 is characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.23(dd,J＝8.0,1.7Hz,1H),7.66(ddd,J＝8.7,7.1,1.7Hz,1H),7.47–7.35(m,5H),7.28–7.26(m,2H),2.57(t,J＝7.7Hz,2H),1.69(dq,J＝9.1,7.6Hz,2H),1.36–1.25(m,2H),0.85(t,J＝7.3Hz,3H)；¹³C NMR(100MHz,CDCl₃):δ177.23,166.79,156.15,133.44,133.29,130.57,128.54,127.88,126.43,124.91,123.71,123.63,117.81,32.42,29.71,22.43,13.84；HRMS(ESI-TOF):calc’d for C₁₉H₁₈NaO₂ ⁺[M+Na⁺]301.1199,found301.1200.

the product obtained in example 59 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.23(dd,J＝8.0,1.7Hz,1H),7.67(ddd,J＝8.8,7.0,1.7Hz,1H),7.47–7.35(m,5H),7.28–7.26(m,2H),3.35(t,J＝6.2Hz,2H),3.26(s,3H),2.69–2.65(m,2H),2.01–1.94(m,2H)；¹³C NMR(100MHz,CDCl₃):δ177.19,166.10,156.13,133.52,133.11,130.54,128.60,127.97,126.45,124.99,123.91,123.63,117.82,71.65,58.65,29.63,27.53；HRMS(ESI-TOF):calc’d for C₁₉H₁₈NaO₃ ⁺[M+Na⁺]317.1148,found 317.1145.

the product obtained in example 60 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.23(dd,J＝7.9,1.7Hz,1H),7.67(ddd,J＝8.7,7.1,1.8Hz,1H),7.47–7.35(m,5H),7.29–7.26(m,2H),3.62(t,J＝6.3Hz,2H),2.71–2.69(t,J＝7.6Hz,2H),1.99–1.92(m,2H),1.59(s,1H)；¹³C NMR(100MHz,CDCl₃):δ177.15,165.99,156.12,133.58,133.08,130.49,128.69,128.06,126.46,125.05,123.95,123.60,117.80,61.90,30.41,29.21；HRMS(ESI-TOF):calc’d for C₁₈H₁₆NaO₃ ⁺[M+Na⁺]303.0992,found 303.0987.

the product obtained in example 61 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.24(dd,J＝8.0,1.7Hz,1H),7.69(ddd,J＝8.7,7.1,1.8Hz,1H),7.48–7.38(m,5H),7.27–7.24(m,2H),2.77–2.74(m,2H),2.36(t,J＝7.2Hz,2H),2.07(p,J＝7.3Hz,2H)；¹³C NMR(100MHz,CDCl₃):δ176.97,163.62,156.00,133.83,132.51,130.36,128.87,128.35,126.55,125.32,124.57,123.58,118.78,117.81,31.48,23.45,16.97；HRMS(ESI-TOF):calc’d for C₁₉H₁₅NNaO₂ ⁺[M+Na⁺]312.0995,found 312.0992.

the product obtained in example 62 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.23(dd,J＝7.9,1.7Hz,1H),7.67(ddd,J＝8.7,7.1,1.7Hz,1H),7.47–7.35(m,5H),7.27–7.25(m,2H),4.05(q,J＝7.1Hz,2H),2.64(t,J＝7.6Hz,2H),2.31(t,J＝7.4Hz,2H),2.04(p,J＝7.5Hz,2H),1.20(t,J＝7.1Hz,3H)；¹³C NMR(100MHz,CDCl₃):δ177.14,172.83,165.34,156.09,133.59,132.96,130.50,128.65,128.03,126.45,125.06,124.13,123.59,117.86,60.63,33.57,31.91,22.73,14.30；HRMS(ESI-TOF):calc’d for C₂₁H₂₀NaO₄ ⁺[M+Na⁺]359.1254,found359.1246.

the product obtained in example 63 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.24(dd,J＝7.9,1.7Hz,1H),7.67(ddd,J＝8.6,7.1,1.7Hz,1H),7.48–7.36(m,5H),7.27–7.25(m,2H),3.46(t,J＝6.4Hz,2H),2.62(t,J＝7.5Hz,2H),1.92–1.82(m,2H),1.83–1.73(m,2H)；¹³C NMR(100MHz,CDCl₃):δ177.14,165.66,156.11,133.60,133.03,130.51,128.68,128.06,126.47,125.07,124.02,123.62,117.83,44.41,31.89,31.80,24.74；HRMS(ESI-TOF):calc’d for C₁₉H₁₇ClNaO₂ ⁺[M+Na⁺]335.0809,found335.0803.

the product obtained in example 64 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.23(dd,J＝8.0,1.7Hz,1H),7.66(ddd,J＝8.7,7.1,1.7Hz,1H),7.47–7.35(m,5H),7.28–7.26(m,2H),4.87(t,J＝4.3Hz,1H),4.01–3.77(m,4H),2.75–2.71(m,2H),2.11–2.04(m,2H)；¹³C NMR(100MHz,CDCl₃):δ177.18,165.65,156.11,133.53,132.98,130.51,128.59,128.00,126.45,125.00,123.81,123.64,117.82,103.32,65.14,31.23,27.13；HRMS(ESI-TOF):calc’d for C₂₀H₁₈NaO₄ ⁺[M+Na⁺]345.1097,found 345.1092.

the product obtained in example 65 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ8.23(dd,J＝8.0,1.7Hz,1H),7.68(ddd,J＝8.6,7.1,1.8Hz,1H),7.48(d,J＝8.4Hz,1H),7.42–7.35(m,4H),7.10–7.07(m,2H),6.83(s,1H),6.76(dd,J＝8.1,1.9Hz,1H),6.63(d,J＝8.1Hz,1H),4.52(t,J＝8.6Hz,2H),3.10(t,J＝8.7Hz,2H),2.98–2.90(m,2H),2.87–2.77(m,2H)；¹³C NMR(100MHz,CDCl₃):δ177.19,165.45,158.82,156.10,133.54,132.99,132.08,130.51,128.47,127.97,127.91,127.33,126.47,125.00,124.97,124.26,123.63,117.78,109.24,71.32,35.13,33.06,29.84；HRMS(ESI-TOF):calc’d for C₂₅H₂₀NaO₃ ⁺[M+Na⁺]391.1305,found 391.1301.

the product obtained in example 66 was characterized as follows:

¹H NMR(400MHz,CDCl₃):δ7.85(dd,J＝8.2,3.1Hz,1H),7.48(dd,J＝9.2,4.2Hz,1H),7.44–7.36(m,2H),7.09(td,J＝8.6,2.6Hz,1H),7.04(d,J＝7.6Hz,1H),6.99(dt,J＝9.5,2.1Hz,1H),2.60(q,J＝7.6Hz,2H),1.27(t,J＝7.5Hz,3H)；¹³C NMR(100MHz,CDCl₃):δ176.19,168.04,162.89(d,J＝246.4Hz),159.61(d,J＝246.3Hz),152.38,135.01(d,J＝8.4Hz),130.17(d,J＝8.6Hz),126.24(d,J＝2.9Hz),124.65(d,J＝7.3Hz),121.88(d,J＝25.5Hz),121.64,119.96(d,J＝8.0Hz),117.61(d,J＝21.4Hz),115.12(d,J＝21.0Hz),111.16(d,J＝23.9Hz),26.29,11.99；¹⁹F NMR(376MHz,CDCl₃):δ-113.01,-115.59；HRMS(ESI-TOF):calc’d for C₁₇H₁₂F₂NaO₂ ⁺[M+Na⁺]309.0698,found309.0699.

the product obtained in example 67 was characterized as follows:

¹H NMR(400MHz,DMSO-d6):δ7.91(dd,J＝9.2,4.2Hz,1H),7.80(td,J＝8.6,3.1Hz,1H),7.74(dd,J＝8.3,3.1Hz,1H),7.55(q,J＝7.9Hz,1H),7.31(td,J＝8.9,2.6Hz,1H),7.24–7.14(m,2H),4.98(q,J＝6.8Hz,1H),1.97(d,J＝6.8Hz,3H)；¹³C NMR(100MHz,DMSO-d6):δ175.29,162.16,161.95(d,J＝244.1Hz),159.17(d,J＝244.8Hz),151.65,133.55(d,J＝8.2Hz),130.53(d,J＝8.6Hz),126.12,123.80(d,J＝7.4Hz),123.04(d,J＝25.4Hz),121.21(d,J＝8.5Hz),119.74,117.16,115.37(d,J＝20.9Hz),109.96(d,J＝23.7Hz),42.76,22.07；¹⁹F NMR(376MHz,DMSO-d6):δ-113.04,-114.86；HRMS(ESI-TOF):calc’d for C₁₇H₁₂BrF₂O₂ ⁺[M+H⁺]364.9983,found364.9978.

although the embodiments of the present invention have been shown and described, it is understood that the above embodiments are illustrative and not restrictive, and that those skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention and that the present invention also includes the modifications and changes.