CN110054603B

CN110054603B - Synthetic method of aryl carbon glycoside compound

Info

Publication number: CN110054603B
Application number: CN201910393081.9A
Authority: CN
Inventors: 陈弓; 何刚; 王权权; 安爽; 祝婉君
Original assignee: Nankai University
Current assignee: Nankai University
Priority date: 2019-05-13
Filing date: 2019-05-13
Publication date: 2020-12-01
Anticipated expiration: 2039-05-13
Also published as: CN110054603A

Abstract

The invention relates to a synthesis method of aryl carbon glycoside compounds, which comprises the steps of stirring and reacting an amide raw material, a sugar donor, a divalent palladium metal catalyst, alkali and an organic solvent under heating, and then coolingCooling to room temperature, directly filtering, spin-drying the filtrate, and separating by column chromatography to obtain aryl carbon glycoside compounds. The invention relates to an aromatic hydrocarbon C (sp) catalyzed by Pd²) The method for activating the-H realizes the simple and efficient synthesis of the aryl carbon glycoside compound. The method has good universality and can be applied to a series of substrates such as aryl formic acid, aryl acetic acid, benzylamine, phenol and the like. The method utilizes halogenated sugar as a sugar donor, has simple synthesis steps, is suitable for mass production and application, and the used guide group is not limited to 8-aminoquinoline, p-picolinic acid, 2-aminopyridine oxynitride and the like and can also be used as the guide group of the reaction. The invention provides a new method and thought for synthesizing a series of complex carbon glycoside drugs and natural products, and simplifies the synthesis difficulty of the carbon glycoside.

Description

Synthetic method of aryl carbon glycoside compound

Technical Field

The invention belongs to the technical field of metal catalysis and medicinal chemistry application, and particularly relates to a synthesis method of aryl carbon glycoside compounds.

Background

Carbon glycosides are the generic term for compounds in which the carbon atom replaces the exocyclic oxygen atom of a carbon glycoside bond, are sugar-containing skeletons which are widely present in nature and are widely present in various natural products and drug molecules, and have better enzyme stability and hydrolysis resistance in organisms compared with oxygen glycosides and nitrogen glycosides, so that they also become an important choice for replacing natural oxygen glycoside drugs. For example, in recent years, a series of SGLT2 inhibitors for treating type ii diabetes, including dapagliflozin, canagliflozin, empagliflozin, and the like, have been developed by various pharmaceutical companies. In addition, the presence of carbon glycosides in natural products is very widespread. The natural product actinocongestin was isolated from the soft coral of hawaii as early as 1971 by professor Scheuer, p.j. (fig. 1), and was later found in other marine organisms, and its total synthesis was completed in 1994 by the group of professor y.kishi of the chemical system of harvard university, an example of the earlier carbon glycoside natural products found, and one of the most complex natural products so far. Since then, more and more natural products containing carbon glycosides were discovered in succession, and FIG. 2 lists representative C-glycoside-containing natural products after 1990 (FIG. 2).

At present, the synthesis methods of the carbon glycoside compounds are mainly divided into the following types:

1) the sugar donor forms glycosyl cation (or anion, free radical) species under the condition of an accelerator or an initiator, and the sugar donor and other carbon-containing electrophilic reagents (or electrophilic reagents, free radicals) are subjected to coupling reaction.

2) The carbon glycosides are formed by rearrangement reactions or by building sugar rings.

3) At present, researches are mainly carried out around metal Pd and metal Ni, wherein the method for synthesizing the saturated carbon glycoside by using Pd catalysis mainly comprises that coupling reaction of 1-substituted glycosyl stannate and aryl iodide is realized by using Pd catalysis in the 2016 year of Walczak and the like so as to construct the carbon glycoside (Walczak, M.A., JACS,2016,138,12049). The synthesis method has the following disadvantages: one is the equivalent of accelerator, the use of initiator (including heavy metal mercury salts, silver salts). The second is that the aryl substrate is an aryl metal reagent, which needs to be prepared in advance, such as aryl magnesium bromide and aryl zinc. In addition, aryl metal reagents are sensitive to air and water and are relatively inconvenient to use. Thirdly, the use of equivalent organic metal reagent, the operation is complicated, strict anhydrous and anaerobic conditions are adopted, the atom economy is poor and the environment-friendly development is not facilitated.

In view of the above, carbon glycosides as an important class of compounds have recently received considerable attention from scientists in academic and medicinal chemistry fields, and there is a need for the development of new methods for efficiently constructing carbon glycoside skeletons.

Disclosure of Invention

The invention aims to firstly utilize a carbon-hydrogen bond activation strategy catalyzed by Pd to lead C (sp) through AQ (or other guide groups) without preparing an aryl metal reagent in advance²) the-H activation strategy realizes the glycosylation reaction of aryl substrates such as aryl formic acid, aryl acetic acid, phenol and the like through one-pot reaction, and the reaction provides a new simple and efficient method and thought for preparing the carbon glycoside compounds.

In order to achieve the purpose, the invention adopts the following technical scheme:

a synthetic method of aryl carbon glycoside compounds comprises the following steps: stirring an amide raw material, a sugar donor, a divalent palladium metal catalyst, alkali and an organic solvent at a specified temperature for reaction, cooling to room temperature, directly filtering, spin-drying filtrate, and performing column chromatography separation to obtain the aryl carbon glycoside compound.

As a further improvement of the above embodiment, the reaction raw material for synthesizing the aryl carbon glycoside compound further comprises an additive; the additive is one of isoleucine, acetic acid, pivalic acid, 2-phenylbenzoic acid, dibenzyl phosphate, N-tert-butoxycarbonyl L-valine (N-Boc-L-Val), N-tert-butoxycarbonyl L-proline (N-Boc-Pro) or N-tert-butoxycarbonyl L-serine (N-Boc-Ser) protected by acetic acid or N-acetyl.

As a further improvement of the above example, the amide starting material is

Wherein Aux is

One of (1); ar is aromatic ring or aromatic heterocyclic ring.

As a further improvement of the above example, the sugar donor has the general structural formula

As a further improvement of the above embodiment, the protecting group P in the sugar donor is one of acetyl, benzyl, methyl, t-butyl diphenyl, silyl, benzoyl, allyl, benzylidene acetal, ketal, or methyl ether.

As a further improvement of the above example, the base is one of potassium acetate, potassium carbonate, sodium bicarbonate, silver acetate or silver carbonateOne kind of the material is selected; the organic solvent is benzene solvent, dichloromethane, chloroform, tetrahydrofuran or CCl₄One of (1); the divalent palladium metal catalyst is Pd (OAc)₂、 PdCl₂、PdBr₂Or Pd (MeCN)₂Cl₂One of (1); the benzene series solvent is more than one of toluene, p-xylene, chlorobenzene or tert-butyl benzene.

As a further improvement of the above example, the amide starting material is reacted in the solvent at a concentration of from 0.001M to 5M; the molar ratio of the amide raw material, the sugar donor (equiv), the divalent palladium metal catalyst and the alkali is 1:1.2-3.0:0.05-1.0: 1.5-3.0.

As a further improvement of the above example, the molar ratio of the amide starting material to the additive is from 1:0.2 to 1.0.

As a further modification of the above example, the reaction conditions at the specified temperature with stirring are: the temperature interval is 25-110 ℃; the stirring time is 1-12 hours.

The invention also provides an aryl carbon glycoside compound prepared by the synthesis method of the aryl carbon glycoside compound, which has the following structural general formula:

the invention principle is as follows: in the prior art, an aryl metal reagent plays a role of a nucleophilic reagent and attacks an oxonium intermediate generated in the reaction. According to the invention, an aryl metal reagent does not need to be prepared in advance, the problems of complex preparation and troublesome storage and use of the aryl metal reagent are effectively solved, and the aryl metal reagent is generated in situ by introducing a guide group into a substrate and directly activating an ortho-position C-H bond by using a carbon-hydrogen bond activation strategy of Pd catalysis. The reaction mechanism of the present invention is as follows.

In the invention, C-H activation is carried out on a substrate under the action of Pd to generate a cyclopalladateintermediate II, oxonium intermediate is generated on chloro-sugar under the action of Pd, the oxoaddition reaction is carried out on the oxonium intermediate and the cyclopalladateintermediate II to generate an intermediate III, and the intermediate III is subjected to reduction elimination reaction to generate IV; finally, IV is subjected to proton decomposition to generate a corresponding target product.

Aryl metal reagent structures in the prior art:

although the corresponding carbon glycoside product can be directly obtained by one-step nucleophilic addition reaction of the aryl metal reagent and the oxonium intermediate VI, the problem of poor stereoselectivity exists, and two configurations of alpha and beta are simultaneously generated. However, the carbon glycosidation reaction developed by the inventor has higher stereoselectivity and generates the carbon glycosidation product with single configuration specifically. In addition, the existing method for carrying out the carbon glycosidation reaction by using the aryl metal reagent has longer reaction time, and the developed carbon glycosidation reaction has high reaction efficiency.

Advantageous effects

1. The invention has the advantages of easily obtained commercial reagents, wide raw material source, simple synthesis, low price, convenient operation and treatment and no need of special treatment.

2. According to the invention, an aryl metal reagent is not required to be prepared in advance, the adopted amide raw material is simple and easy to prepare, is insensitive to air and water, is convenient to use, and realizes the glycosylation reaction of substrates such as aryl formic acid, aryl acetic acid and phenol by utilizing a carbon-hydrogen bond activation strategy of Pd catalysis for the first time and utilizing a C (sp2) -H activation strategy of AQ (or other guide groups) guidance.

3. The glycosyl donor adopted by the invention has simple preparation steps, no toxicity, no strict water and oxygen free in the preparation process, and stable and easily obtained receptor structure used in the reaction.

4. The invention has simple operation, does not need strict anhydrous and anaerobic conditions, and can react in a reaction bottle by a one-pot method to obtain a corresponding target product by one-step reaction. The method has simple requirements on equipment and no special requirements on post-treatment, and greatly reduces the production cost for synthesizing the compounds.

5. The method has simple treatment after reaction, and can be obtained by spin-drying the solvent and performing simple column chromatography separation after the reaction is finished.

6. The amide raw material of the present invention has a reaction concentration of 0.001 to 5M, and is suitable for mass production.

7. The invention does not need to add an equivalent accelerating agent in the reaction, the initiator is used, the accelerating agent utilized by the prior method plays a role in activating the sugar donor, and the catalytic amount of the metal palladium catalyst used in the invention can not only promote the hydrocarbon activation reaction, but also can be used as a Lewis acid activated sugar donor.

8. The method uses less metal palladium catalyst, maintains good catalytic effect, and simultaneously achieves the requirements of simplifying process, reducing cost, facilitating post-treatment process, facilitating the recycling of solvent, reducing environmental pollution and the like.

9. The additive of the invention is used for accelerating proton decomposition (formula IV to formula V) and promoting reaction.

Drawings

FIG. 1 shows the structure of natural product actinocongestin;

FIG. 2 is a representation of the C-glycoside natural product found after 1990;

FIG. 3 is a general reaction scheme of the preparation method of the present invention;

FIG. 4 is a diagram showing the structure of a specific compound corresponding to the amide starting material;

FIG. 5 is a structural diagram of a specific compound corresponding to a sugar donor;

FIG. 6 is a diagram showing the structure of a specific compound corresponding to the product.

Detailed description of the invention

The following examples will better illustrate the invention, but it should be emphasized that the invention is in no way limited to what is shown in these examples. The following examples show different aspects of the invention. The data presented include specific operating and reaction conditions and products. The purity of the product was identified by nuclear magnetism.

Examples 1 to 9

In an 8ml reaction flask, 1-s (26.2mg,0.1mmol, 1.0equiv) of an amide raw material, chloro-sugar (Donor-1) (112mg,0.2 mmol,2.0equiv), palladium acetate (2.2mg,0.01mmol,0.1equiv), acetylisoleucine (Ac-Ile-OH) (5.2mg,0.03mmol,0.3equiv), potassium acetate (14.7mg,0.15mmol,1.5equiv) were sequentially added, 1ml of a solvent was added, a reaction flask was capped (no particularly strict anhydrous oxygen-free condition was required), and stirring was carried out at 60 ℃ for 6 hours. And (3) cooling the reaction bottle to room temperature after the reaction is completed, filtering, concentrating, and performing column chromatography separation to obtain a colorless oily product. The preparation procedures of examples 1-9 are essentially the same except that a reaction solvent is used.

TABLE 1 examination of reaction solvents

a:NMR Yield

It can be seen from examples 1-9 that the best yield of example 6 is obtained when the reaction solvent is PhMe.

Examples 10 to 17

The preparation methods of examples 10-17 are substantially the same as those of example 6, except that the divalent palladium metal catalyst used in examples 10-17 is different, as shown in Table 2

TABLE 2 divalent Palladium Metal catalyst screening

a：NMR Yield

From examples 10 to 17, it can be found that when the divalent palladium metal catalyst is Pd (OAc)₂The best yield of example 6 was obtained.

Examples 18 to 23

The preparation of examples 18 to 23 was carried out in substantially the same manner as in example 6, except that the bases used in examples 18 to 23 were different, as shown in Table 3.

TABLE 3 examination of bases

a：NMR Yield

It can be seen from examples 18 to 23 that the best yield of example 6 is obtained when the base is potassium acetate.

Examples 24 to 30

The preparation methods of examples 24-30 are substantially the same as those of example 6, except that the additives selected in examples 24-30 are different, as shown in Table 4

TABLE 4 examination of additives

a:NMR Yield

It can be seen from examples 24-30 that the best yield from example 6 is obtained when the additive is Ac-Ile-OH.

Examples 31 to 34

The preparation methods of examples 31 to 34 were substantially the same as those of example 6 except that the reaction temperatures used in examples 31 to 34 were different, as shown in Table 5

TABLE 5 examination of reaction temperature

a：NMR Yield

It can be seen from examples 31 to 34 that the yield of example 6 is the best when the reaction temperature is 60 ℃.

Examples 35 to 38

The preparation of examples 35-38 was substantially the same as that of example 6, except that the reaction times used in examples 35-38 were different, as shown in Table 6.

TABLE 6 examination of reaction time

a:NMR Yield

From examples 35 to 38, it was found that the yield of example 6 was the best when the reaction time was 6 hours.

Examples 39 to 66

In an 8ml reaction flask, the amide starting material (0.1mmol, 1.0equiv), the sugar donor (0.2mmol,2.0equiv), palladium acetate (2.2mg,0.01mmol,0.1equiv), Ac-Ile-OH (5.2mg,0.03mmol,0.3equiv), potassium acetate (14.7mg,0.15mmol,1.5equiv) were sequentially charged, 1ml of toluene was added as a solvent, a reaction flask cap was closed (no particularly strict anhydrous oxygen-free condition was required), and stirring was carried out under heating. And (3) cooling the reaction bottle to room temperature after the reaction is completed, filtering, concentrating, and performing column chromatography separation to obtain the product. The specific reaction conditions for examples 39-66 are shown in Table 7, wherein the general reaction scheme is shown in FIG. 3, the amide starting material is shown in FIG. 4, the sugar donor is shown in FIG. 5, and the product is shown in FIG. 6.

II, product structure characterization

Product 1:

¹H NMR(400MHz,Chloroform-d)10.47(s,1H),9.01–8.81(m,1H),8.63(dd,J＝4.2,1.7Hz,1H),8.09(dd, J＝8.3,1.7Hz,1H),7.69–7.00(m,24H),6.87(2s,2H),5.57(d,J＝7.2Hz,1H),4.83–4.18(m,9H),4.08(dd, J＝7.2,2.6Hz,1H),3.97(q,J＝5.3Hz,1H),3.82(dd,J＝5.5,3.8Hz,1H),3.79–3.70(m,2H),3.64(dd,J＝ 10.3,5.7Hz,1H),2.39(s,3H).

¹³C NMR(101MHz,CDCl₃)168.64,148.10,139.05,138.52,138.31,138.28,138.20,137.82,137.60,136.17, 135.07,133.66,130.74,128.39,128.34,128.21,128.14,128.08,128.03,127.80,127.73,127.59,127.42,127.39, 127.32,127.26,121.87,121.44,117.54,77.42,77.10,76.83,76.78,75.78,75.22,74.97,73.28,72.48,72.35, 71.55,69.96,68.60,21.13.

and (3) a product 2:

¹H NMR(400MHz,Chloroform-d)10.49(s,1H),8.94(d,J＝7.6Hz,1H),8.62(d,J＝4.2Hz,1H),8.09(d,J＝ 8.2Hz,1H),7.56(t,J＝7.9Hz,1H),7.49(m,2H),7.39–7.06(m,21H),6.88(m,2H),5.56(d,J＝7.1Hz,1H), 4.57–4.18(m,8H),4.12(d,J＝7.2Hz,1H),3.96(m,1H),3.84(t,J＝4.8Hz,1H),3.75(m,2H),3.65(dd,J＝ 10.4,5.8Hz,1H),2.96(m,1H),1.30(s,3H),1.28(s,3H).

¹³C NMR(101MHz,CDCl₃)169.54,149.47,148.79,139.78,139.23,138.99,138.90,138.40,136.85,135.82, 134.57,129.04,128.90,128.85,128.78,128.69,128.54,128.45,128.29,128.11,128.02,127.96,126.75,122.55, 122.12,118.25,78.11,77.99,77.79,77.47,76.45,75.87,75.67,73.99,73.17,73.11,72.16,70.84,69.32,34.55, 24.68,24.58.

and (3) a product:

¹H NMR(400MHz,Chloroform-d)11.38(s,1H),8.80(d,J＝7.6Hz,1H),8.70(d,J＝4.1Hz,1H),8.02(d,J ＝8.3Hz,1H),7.92(d,J＝8.1Hz,1H),7.57(t,J＝7.9Hz,1H),7.48(d,J＝8.2Hz,1H),7.40–7.15(m,11H), 7.14–6.88(m,11H),6.77(m,2H),5.58(d,J＝9.7Hz,1H),4.58–4.19(m,8H),4.15–3.87(m,6H),3.84– 3.72(m,2H),3.67(d,J＝4.0Hz,1H).

¹³C NMR(101MHz,CDCl₃)161.46,148.30,140.01,138.52,138.34,138.07,137.92,136.00,135.00,132.51, 128.36,128.34,128.30,127.96,127.94,127.53,127.46,127.44,127.33,127.11,127.07,126.96,126.18,123.95, 122.67,121.98,121.42,120.17,119.04,114.85,109.84,77.46,77.35,77.14,76.83,75.52,74.87,74.84,74.60, 73.07,73.02,72.30,70.82,68.08,65.79,31.54.

and (3) a product 4:

¹H NMR(400MHz,Chloroform-d)11.10(s,1H),9.00(dd,J＝7.4,1.7Hz,1H),8.93(dd,J＝4.2,1.6Hz, 1H),8.18(dd,J＝8.2,1.7Hz,1H),7.97(d,J＝7.9Hz,1H),7.75–7.53(m,3H),7.48(dd,J＝8.3,4.2Hz,1H), 7.41(t,J＝7.8Hz,1H),7.37–7.13(m,15H),7.07–6.89(m,5H),6.31(d,J＝9.3Hz,1H),4.85(d,J＝12.2Hz, 1H),4.73–4.43(m,5H),4.38(dd,J＝9.3,2.8Hz,1H),4.33(t,J＝6.8Hz,1H),4.22(m,2H),4.08(dd,J＝10.0, 6.9Hz,1H),4.03–3.94(m,2H),3.88(dd,J＝4.3,1.8Hz,1H).

¹³C NMR(101MHz,CDCl₃)157.65,153.83,148.50,144.54,138.95,138.64,138.60,138.33,137.99,136.32, 134.41,128.42,128.32,128.29,128.09,127.91,127.85,127.69,127.66,127.59,127.56,127.50,127.43,127.37, 127.26,126.99,124.68,123.99,123.41,122.04,121.71,117.34,111.96,77.39,77.07,76.76,75.09,74.25,73.28, 73.08,71.64,71.61,68.44,65.49.

and (3) a product 5:

¹H NMR(400MHz,Chloroform-d)10.23(s,1H),8.75(dd,J＝7.3,1.8Hz,1H),8.62(dd,J＝4.2,1.7Hz,1H), 8.06(dd,J＝8.3,1.7Hz,1H),7.88(s,1H),7.57–7.38(m,2H),7.37–7.05(m,20H),6.96(m,2H),5.11(d,J＝ 9.0Hz,1H),4.70(d,J＝12.2Hz,1H),4.59(m,3H),4.45(m,3H),4.38–4.25(m,3H),4.23–4.09(m,4H),4.04 (dd,J＝9.1,3.0Hz,1H),3.99(t,J＝3.8Hz,1H),3.92(m,3H),3.70(d,J＝14.0Hz,1H),1.46(m,3H),1.36(m, 3H).

¹³C NMR(101MHz,CDCl₃)169.51,166.00,158.28,148.13,140.33,138.66,138.28,138.25,138.03,137.74, 136.10,135.00,133.15,129.15,128.42,128.33,128.20,128.01,127.94,127.88,127.76,127.72,127.58,127.55, 127.24,121.52,121.45,118.77,116.76,115.71,77.43,77.11,76.79,75.35,74.46,74.43,73.19,72.91,71.90, 71.75,71.47,68.05,64.75,60.67,42.22,14.75,14.40.

product 6-1:

¹H NMR(400MHz,Chloroform-d)10.16(s,1H),8.80(d,J＝7.5Hz,1H),8.50(d,J＝4.2Hz,1H),8.03(d,J ＝8.2Hz,1H),7.95(s,1H),7.82(m,2H),7.76–7.63(m,1H),7.56–6.98(m,23H),6.89(m,2H),5.38(d,J＝ 8.1Hz,1H),4.81–4.49(m,4H),4.45–4.26(m,4H),4.24–3.96(m,5H),3.90(m,3H).

¹³C NMR(101MHz,CDCl₃)170.21,148.03,138.59,138.48,138.41,138.16,137.83,136.04,135.65,135.00, 133.13,132.39,132.36,130.07,128.45,128.41,128.30,128.25,128.10,127.95,127.89,127.82,127.73,127.69, 127.48,127.43,127.40,127.31,126.22,125.84,121.39,121.32,116.53,77.39,77.27,77.07,76.75,76.52,75.13, 75.01,74.83,73.17,72.84,72.31,71.84,71.66,68.39,42.58.

and (3) products 6-2:

¹H NMR(400MHz,Chloroform-d)9.96(s,1H),8.77(dd,J＝7.6,1.5Hz,1H),8.43(m,2H),8.01(dd,J＝8.3, 1.7Hz,1H),7.86(dd,J＝8.3,1.4Hz,1H),7.57–7.36(m,5H),7.34–7.21(m,15H),7.17(dd,J＝8.3,4.3Hz, 1H),7.10–6.94(m,3H),6.88–6.77(m,2H),5.62(d,J＝7.3Hz,1H),4.70(d,J＝12.4Hz,1H),4.65–4.40(m, 5H),4.25(dd,J＝7.3,2.9Hz,1H),4.09(dd,J＝6.4,3.6Hz,1H),4.04(m,2H),4.01(dd,J＝5.4,2.9Hz,1H), 3.98–3.91(m,4H),3.77(dd,J＝10.2,5.2Hz,1H).

¹³C NMR(101MHz,CDCl₃)169.34,148.28,138.49,138.38,138.24,137.95,136.17,136.06,134.38,134.28, 131.31,131.20,129.11,128.43,128.41,128.34,127.99,127.83,127.81,127.70,127.67,127.51,127.33,127.28, 125.98,125.89,125.33,121.61,121.47,116.31,77.40,77.08,76.76,76.22,75.44,74.88,73.11,72.94,72.47, 72.20,68.22,45.43.

and (3) a product 7:

¹H NMR(400MHz,Chloroform-d)10.25(s,1H),8.93(dd,J＝5.7,3.3Hz,1H),8.81(dd,J＝4.2,1.7Hz,1H), 8.20(dd,J＝8.3,1.7Hz,1H),7.79(d,J＝8.1Hz,1H),7.67–7.44(m,4H),7.43–7.01(m,17H),5.83(d,J＝3.1 Hz,1H),5.64(dd,J＝4.8,3.1Hz,1H),4.88(d,J＝11.5Hz,1H),4.63(m,2H),4.50(d,J＝11.3Hz,1H),4.40(d, J＝12.2Hz,1H),4.26(d,J＝12.2Hz,1H),4.03(m,2H),3.80(dd,J＝7.2,5.4Hz,1H),3.73(dd,J＝10.5,4.7 Hz,1H),3.66(dd,J＝10.6,4.0Hz,1H),3.00(m,1H),1.94(s,3H),1.33(2s,6H).

¹³C NMR(101MHz,CDCl₃)167.99,148.62,148.33,138.21,136.30,135.94,134.86,134.14,129.19,128.31, 128.14,128.07,128.00,127.94,127.89,127.78,127.65,127.57,127.44,127.30,125.24,121.73,121.62,116.79, 77.90,77.34,77.23,77.03,76.71,76.01,74.43,73.38,73.10,72.54,71.75,69.22,69.06,33.78,23.95,23.80, 21.03.

and (3) a product 8:

¹H NMR(400MHz,Chloroform-d)10.26(s,1H),8.87(d,J＝7.0Hz,1H),8.76(d,J＝4.2Hz,1H),8.18(d,J ＝8.2Hz,1H),7.87(d,J＝8.1Hz,1H),7.75–6.81(m,25H),5.69(s,1H),4.76–4.28(m,7H),4.25(d,J＝4.6 Hz,1H),4.11(m,4H),3.83–3.63(m,2H),3.02(m,1H),1.35(s,1H),1.33(s,1H).

¹³C NMR(101MHz,CDCl₃)168.15,148.32,148.07,138.68,138.64,138.58,138.13,136.31,135.05,134.94, 134.89,129.94,128.27,128.18,128.10,128.08,128.00,127.92,127.64,127.51,127.48,127.45,127.41,127.13, 124.45,121.71,121.67,116.60,77.66,77.36,77.25,77.05,76.73,75.47,75.18,73.54,73.16,72.98,72.01,71.61, 67.48,66.07,33.81,24.08,23.98.

and (3) a product:

¹H NMR(400MHz,Chloroform-d)10.05(s,1H),8.95(d,J＝7.4Hz,1H),8.72(dd,J＝4.1,1.9Hz,1H),8.15 (dd,J＝8.4,2.0Hz,1H),7.63–7.50(m,2H),7.50–7.36(m,2H),7.38–7.23(m,12H),7.16(m,1H),7.00(d,J ＝8.1Hz,1H),6.03(t,J＝2.9Hz,1H),5.59(d,J＝3.0Hz,1H),4.88–4.69(m,2H),4.65(dd,J＝11.6,1.7Hz, 1H),4.52(d,J＝10.9Hz,1H),3.91(dd,J＝8.0,3.1Hz,1H),3.54–3.30(m,2H),2.94(m,1H),2.12(s,3H), 1.28(s,3H),1.26(s,3H),1.06(dd,J＝6.0,1.7Hz,3H).

¹³C NMR(101MHz,CDCl₃)170.57,168.83,149.32,148.19,138.50,138.27,137.92,137.41,136.34,134.74, 132.27,128.51,128.41,128.37,128.26,127.98,127.95,127.77,127.74,127.58,127.13,126.42,121.71,121.60, 116.90,80.52,77.41,77.30,77.17,77.09,76.77,74.91,73.07,72.24,70.61,69.55,33.74,23.96,23.70,21.29, 17.63.

and (3) a product:

¹H NMR(400MHz,Chloroform-d)10.31(s,1H),8.91(t,J＝4.5Hz,1H),8.81(d,J＝4.2Hz,1H),8.16(d,J＝ 8.2Hz,1H),7.80(d,J＝8.2Hz,1H),7.53(m,3H),7.45(dd,J＝8.3,4.2Hz,1H),7.38–7.26(m,11H),5.55(s, 1H),5.52(s,1H),4.87(d,J＝11.6Hz,1H),4.57–4.44(m,3H),4.14(d,J＝12.7Hz,1H),3.98(m,2H),3.35(s, 1H),2.99(m,1H),1.92(s,3H),1.32(s,3H),1.30(s,3H).

¹³C NMR(101MHz,CDCl₃)170.67,167.77,148.46,148.36,138.71,138.22,138.03,136.26,135.08,134.89, 134.73,129.20,128.33,128.25,128.02,127.99,127.66,127.62,127.59,127.36,124.59,121.72,121.64,116.59, 77.33,77.02,76.70,73.22,73.13,71.79,71.14,70.90,69.18,67.57,33.80,29.71,23.94,23.84,21.02.

and (3) a product 11:

¹H NMR(400MHz,Chloroform-d)10.33(s,1H),8.98–8.89(m,1H),8.81(dd,J＝4.3,1.6Hz,1H),8.17(dd, J＝8.4,1.7Hz,1H),7.60(d,J＝8.1Hz,1H),7.56–7.50(m,3H),7.43(m,3H),7.38–7.18(m,9H),5.75(d,J＝ 3.8Hz,1H),5.57(s,1H),4.90(d,J＝11.9Hz,1H),4.67(d,J＝11.8Hz,1H),4.48(m,2H),4.05–3.89(m,3H), 3.85(m,1H),2.98(m,J＝6.9Hz,1H),1.89(s,3H),1.31(s,3H),1.29(s,3H).

¹³C NMR(101MHz,CDCl₃)169.69,167.65,148.55,148.39,138.71,138.32,138.23,136.33,135.20,134.86, 134.21,128.56,128.54,128.37,128.16,128.11,128.01,127.98,127.70,127.68,127.61,127.42,124.77,121.80, 121.67,116.65,77.38,77.06,76.74,72.72,72.22,71.86,71.73,70.94,70.76,65.19,33.77,23.92,23.86,20.88.

product 12:

¹H NMR(400MHz,Chloroform-d)10.28(s,1H),8.94(dd,J＝7.2,1.7Hz,1H),8.79(dd,J＝4.2,1.7Hz,1H), 8.19(dd,J＝8.3,1.7Hz,1H),7.73–7.54(m,3H),7.46(dd,J＝8.3,4.2Hz,1H),7.36(s,2H),5.71(d,J＝1.3Hz, 1H),4.99(dd,J＝6.0,1.4Hz,1H),4.78(dd,J＝6.0,3.9Hz,1H),4.44(m,1H),4.17(dd,J＝8.8,4.4Hz,1H), 4.07(dd,J＝8.7,6.3Hz,1H),3.93(dd,J＝7.8,3.9Hz,1H),3.00(m,1H),1.46(s,3H),1.40(s,3H),1.36(s,3H), 1.31(s,3H),1.30(s,3H),1.24(s,3H).

¹³C NMR(101MHz,CDCl₃)167.99,148.30,138.74,136.37,136.03,134.63,134.23,128.51,128.01,127.43, 126.67,126.55,121.95,121.66,117.02,112.70,109.17,86.90,83.80,81.31,80.99,77.38,77.06,76.74,73.58, 67.04,33.77,29.72,26.94,26.25,25.24,24.69,23.95,23.79.

product 13:

¹H NMR(400MHz,Chloroform-d)10.53(s,1H),8.89(dd,J＝6.9,2.1Hz,1H),8.79(dd,J＝4.2,1.7Hz,1H), 8.17(dd,J＝8.3,1.7Hz,1H),7.61(m,3H),7.49–7.39(m,2H),7.36(t,1H),7.25–7.17(m,1H),5.64(d,J＝ 1.8Hz,1H),5.38(dd,J＝5.9,1.8Hz,1H),5.09(dd,J＝5.9,3.9Hz,1H),4.45(m,1H),4.25(dd,J＝8.7,4.6Hz, 1H),4.07(m,2H),3.94(s,3H),1.45(s,3H),1.35(m,9H).

¹³C NMR(101MHz,CDCl₃)161.15,148.49,139.07,137.74,136.23,134.36,133.59,128.13,127.19,125.03, 123.92,122.64,121.75,120.92,120.31,117.88,113.20,113.01,110.46,109.27,85.45,81.89,81.16,80.28,77.37, 77.26,77.05,76.74,73.47,67.06,31.32,26.98,26.31,25.43,24.83.

product 14:

¹H NMR(400MHz,Chloroform-d)10.22(s,1H),8.88(dd,J＝6.1,3.0Hz,1H),8.81(dd,J＝4.3,1.7Hz,1H), 8.19(dd,J＝8.3,1.7Hz,1H),8.04(d,J＝1.9Hz,1H),7.83(dd,J＝8.2,1.8Hz,1H),7.58(s,1H),7.48(dd,J＝ 8.3,4.3Hz,1H),7.21(d,J＝8.2Hz,1H),5.63(s,1H),4.93(dd,J＝6.0,1.7Hz,1H),4.75(dd,J＝6.0,4.0Hz, 1H),4.52–4.23(m,1H),4.24–4.04(m,2H),3.91(dd,J＝7.6,3.9Hz,1H),1.45(s,3H),1.38(s,3H),1.35(s, 3H),1.21(s,3H).

¹³C NMR(101MHz,CDCl₃)165.85,148.43,139.47,138.63,137.72,137.07,136.71,136.42,134.24,128.47, 127.99,127.36,122.30,121.77,117.11,112.99,109.17,93.19,86.93,83.94,81.65,80.93,77.39,77.28,77.07, 76.76,73.51,66.87,26.87,26.35,25.25,24.78.

product 15:

¹H NMR(400MHz,Chloroform-d)11.08(s,1H),9.01–8.86(m,2H),8.18(m,1H),8.02(d,J＝7.9Hz,1H), 7.73(m,4H),7.66(d,J＝8.4Hz,1H),7.61–7.52(m,2H),7.49(m,1H),7.41(m,3H),7.35(m,4H),6.98(t,J＝ 7.5Hz,1H),6.25(dd,J＝5.9,1.4Hz,1H),5.08(m,1H),4.99–4.87(m,1H),4.21(m,1H),4.12(m,1H),3.99 (m,1H),1.74(s,3H),1.39(s,3H),1.15(s,9H).

¹³C NMR(101MHz,CDCl₃)157.44,153.94,148.54,144.13,138.80,136.34,135.78,135.62,134.18,133.38, 132.90,129.86,129.72,128.04,127.86,127.78,127.35,127.32,126.84,124.26,123.69,123.56,122.09,121.75, 117.16,115.51,112.05,85.59,84.54,80.90,77.91,77.37,77.26,77.05,76.73,63.56,27.70,27.06,25.82,19.44 product 16:

¹H NMR(400MHz,Chloroform-d)11.00(s,1H),8.90(dd,J＝7.1,1.7Hz,1H),8.72(t,J＝2.7Hz,1H),8.13 (dd,J＝8.3,1.6Hz,1H),7.65(m,4H),7.58–7.48(m,2H),7.42–7.31(m,7H),7.25(m,2H),5.60(d,J＝5.5 Hz,1H),4.91(m,2H),4.41(d,J＝3.6Hz,1H),3.95(m,2H),1.56(s,3H),1.39(s,3H),1.04(s,9H).

¹³C NMR(101MHz,CDCl₃)160.53,148.25,141.15,139.10,137.05,136.22,135.75,135.66,135.59,135.06, 133.28,133.11,129.78,129.70,128.49,128.07,128.04,127.75,127.67,127.36,121.96,121.53,117.74,114.82, 85.24,84.31,81.59,79.67,77.37,77.26,77.05,76.74,63.80,27.68,26.88,25.80,19.30.

product 17:

¹H NMR(400MHz,Chloroform-d)10.11(s,1H),8.76(dd,J＝7.2,1.7Hz,1H),8.65(dd,J＝4.2,1.7Hz,1H), 8.09(dd,J＝8.3,1.6Hz,1H),7.65(m,4H),7.54–7.40(m,2H),7.40–7.27(m,7H),7.27–7.15(m,1H),7.10 (d,J＝5.3Hz,1H),5.10(d,J＝5.8Hz,1H),4.77(dd,J＝6.8,3.8Hz,1H),4.62(m,1H),4.36–4.16(m,2H), 4.07(m,1H),3.96(dd,J＝11.2,3.7Hz,1H),3.88(dd,J＝11.2,3.9Hz,1H),1.55(s,3H),1.19(s,3H),1.03(s, 9H).

¹³C NMR(101MHz,CDCl₃)168.38,148.09,138.65,137.75,136.17,135.65,135.62,134.65,133.22,133.18, 131.61,129.80,129.74,127.88,127.77,127.72,127.33,126.51,124.61,121.61,121.47,116.71,114.80,86.07, 84.35,82.01,81.59,77.41,77.09,76.78,63.88,37.49,27.59,26.86,25.42,19.29.

product 18:

¹H NMR(400MHz,Chloroform-d)10.20(s,1H),8.92(dd,J＝6.5,2.5Hz,1H),8.71(dd,J＝4.2,1.7Hz,1H), 8.14(dd,J＝8.3,1.7Hz,1H),7.65(m,5H),7.57–7.47(m,3H),7.45–7.29(m,7H),7.26(dd,J＝8.2,2.0Hz, 1H),5.35(d,J＝4.7Hz,1H),4.88–4.72(m,2H),4.08(m,1H),3.90(dd,J＝11.1,3.9Hz,1H),3.78(dd,J＝ 11.1,4.0Hz,1H),2.96(m,1H),1.32(s,3H),1.29(s,3H),1.27(s,3H),1.21(s,3H),1.03(s,9H).

¹³C NMR(101MHz,CDCl₃)168.26,148.87,148.20,138.70,136.41,136.24,135.66,135.10,133.43,133.26, 129.70,129.65,128.42,127.96,127.71,127.54,127.39,125.45,121.73,121.58,116.87,114.38,86.84,84.27, 82.87,81.56,77.39,77.28,77.08,76.76,63.91,33.86,27.43,26.86,26.84,25.63,23.95,23.89.

product 19:

¹H NMR(400MHz,Chloroform-d)10.52(s,1H),8.95(d,J＝7.5Hz,1H),8.66(d,J＝4.2Hz,1H),8.15(dd,J ＝8.4,1.6Hz,1H),7.61(m,1H),7.58–7.48(m,2H),7.41(m,2H),7.31(m,4H),7.11(m,8H),7.01(m,2H), 6.88(m,2H),5.52(d,J＝7.7Hz,1H),5.47–5.28(m,4H),5.24(d,J＝4.1Hz,1H),5.17(t,J＝9.1Hz,1H),5.09 (t,J＝9.8Hz,1H),4.88(dd,J＝10.5,4.1Hz,1H),4.81–4.67(m,2H),4.51–4.40(m,2H),4.36(m,2H),4.33– 4.20(m,6H),4.15(m,2H),4.11–4.02(m,2H),4.02–3.84(m,7H),3.70(dd,J＝5.1,2.5Hz,1H),3.65(d,J＝ 5.2Hz,1H),3.47–3.35(m,1H),2.98(m,1H),2.15(s,3H),2.10(s,3H),2.07(s,3H),2.07(s,3H),2.04(s,3H), 2.02(s,3H),2.01(2s,6H),1.95(s,3H),1.80(s,3H),1.31(d,J＝2.3Hz,3H),1.29(d,J＝2.2Hz,3H).

¹³C NMR(101MHz,CDCl₃)170.67,170.60,170.52,170.34,170.00,169.96,169.79,169.71,169.45,168.65, 148.74,148.15,139.00,138.13,138.11,138.07,137.55,136.21,135.06,133.84,128.37,128.20,128.09,128.07, 127.98,127.91,127.63,127.54,127.49,127.37,127.35,127.28,125.92,121.93,121.48,117.35,100.89,95.73, 95.69,77.46,77.34,77.14,76.89,76.82,75.38,75.21,75.07,73.80,72.55,72.42,72.30,72.07,71.80,71.73, 71.45,70.43,70.12,69.77,69.41,68.87,68.72,68.50,67.93,63.00,62.30,61.39,33.81,23.91,20.92,20.89, 20.83,20.68,20.61,20.40.

and (3) a product 20:

¹H NMR(400MHz,Chloroform-d)12.07(s,1H),9.13(dd,J＝7.7,1.4Hz,1H),8.84(dd,J＝4.2,1.7Hz, 1H),8.41(s,1H),8.17(dd,J＝8.3,1.7Hz,1H),7.63–7.45(m,3H),7.41–7.23(m,15H),7.05(m,7H),6.99– 6.88(m,2H),6.82(m,2H),5.47–5.36(m,1H),5.09(d,J＝9.2Hz,1H),4.70(d,J＝12.0Hz,1H),4.65–4.39 (m,6H),4.33–4.08(m,6H),4.05–3.94(m,2H),3.86(dd,J＝10.0,7.3Hz,1H),3.78(dd,J＝4.4,2.1Hz,1H), 3.75–3.69(m,1H),3.37(d,J＝13.6Hz,1H),3.01(m,2H),2.55(s,2H),1.83–1.32(m,12H),0.88(2s,6H).

¹³C NMR(101MHz,CDCl₃)170.07,163.65,156.62,152.28,147.82,141.49,139.45,139.32,138.23,138.19, 138.08,137.94,137.77,136.26,136.10,128.85,128.53,128.42,128.36,128.25,128.18,128.15,128.02,127.97, 127.87,127.83,127.74,127.73,127.70,127.68,127.62,127.29,126.09,124.23,121.49,121.47,121.02,120.23, 117.71,114.48,77.40,77.28,77.08,76.76,74.93,74.63,74.25,73.08,71.93,71.68,67.67,65.42,47.30,46.62, 40.90,29.74,26.72,25.34,24.40,23.07,22.31,14.96.

product 21:

¹H NMR(400MHz,Chloroform-d)9.55(s,1H),8.71(dd,J＝4.2,2.0Hz,1H),8.44(d,J＝7.2Hz,1H),8.15 (dd,J＝8.3,2.1Hz,1H),7.63–7.36(m,3H),7.30–7.07(m,24H),6.99(d,J＝8.0Hz,1H),5.31(dd,J＝6.3, 2.0Hz,1H),4.68–4.26(m,9H),4.14(m,1H),3.92(m,2H),3.87–3.81(m,2H),3.76(m,1H),2.38(s,3H).

¹³C NMR(101MHz,CDCl₃)151.66,148.87,148.20,138.95,138.56,138.51,138.42,138.34,136.18,134.56, 128.32,128.28,128.18,128.16,128.08,128.05,127.89,127.75,127.55,127.51,127.41,127.33,127.28,127.26, 126.66,124.04,121.68,120.98,114.97,77.36,77.04,76.77,76.72,76.11,75.08,75.06,73.19,72.86,72.53, 72.00,69.71,68.79,21.08.

product 22-1:

¹H NMR(400MHz,Chloroform-d)9.54(s,1H),8.68(dd,J＝4.2,1.7Hz,1H),8.46(d,J＝7.3Hz,1H),8.23– 8.00(m,1H),7.59–7.33(m,5H),7.32–7.09(m,20H),5.31(d,J＝6.6Hz,1H),4.62–4.29(m,8H),4.02(t,J＝ 5.2Hz,1H),3.95–3.73(m,5H),1.31(s,9H).

¹³C NMR(101MHz,CDCl₃)151.79,148.67,148.22,146.61,138.52,138.49,138.43,138.38,136.23,134.60, 130.48,128.42,128.38,128.33,128.25,128.21,128.19,128.08,127.89,127.85,127.82,127.76,127.71,127.65, 127.59,127.54,127.40,127.25,125.85,125.78,123.05,121.71,121.02,115.06,77.43,77.31,77.11,76.85,76.79, 75.94,74.92,74.83,73.24,72.70,72.38,72.15,72.03,68.88,34.67,31.62,31.52.

product 22-2:

¹H NMR(400MHz,Chloroform-d)9.57(s,1H),8.61(d,J＝4.2Hz,1H),8.48(t,J＝4.5Hz,1H),8.11(d,J＝8.3Hz,1H),7.57(s,2H),7.53–7.42(m,2H),7.26–6.98(m,41H),5.33(m,2H),4.56–4.20(m,18H),4.04(m, 2H),3.90–3.72(m,8H),1.29(s,9H).

¹³C NMR(101MHz,CDCl₃)151.17,148.80,148.07,144.88,138.55,138.52,138.45,138.41,136.08,134.84, 132.04,128.40,128.31,128.23,128.14,128.11,128.06,128.00,127.82,127.77,127.72,127.66,127.60,127.53, 127.47,127.36,127.29,127.09,125.50,121.65,120.87,115.00,77.44,77.32,77.12,76.97,76.80,76.43,75.18, 74.84,73.23,72.58,72.23,72.00,70.73,69.01,34.83,31.54,29.77.

product 23:

¹H NMR(400MHz,Chloroform-d)11.05(s,1H),8.93(d,J＝7.6Hz,1H),8.82–8.56(m,1H),8.09(d,J＝8.2 Hz,1H),7.64–7.45(m,3H),7.39–7.22(m,17H),7.14(m,10H),6.95(dd,J＝9.5,3.3Hz,1H),6.91–6.72(m, 2H),5.46(d,J＝2.7Hz,1H),4.88(d,J＝11.3Hz,1H),4.64–4.38(m,6H),4.09(m,2H),3.99(s,1H),3.90–3.72(m,5H),3.70–3.50(m,2H).

¹³C NMR(101MHz,CDCl₃)164.30,154.89,149.62,148.23,139.05,138.62,138.54,138.35,138.05,136.39, 135.01,128.38,128.32,128.24,128.22,128.15,128.07,128.02,127.77,127.71,127.64,127.59,127.40,127.06, 126.61,126.42,121.84,121.48,119.39,117.97,117.66,114.75,99.51,78.78,77.35,77.24,77.03,76.72,76.30, 74.92,73.43,73.10,72.24,70.72,68.47,55.84.

product 24:

¹H NMR(400MHz,Chloroform-d)11.05(s,1H),8.93(d,J＝7.6Hz,1H),8.82–8.56(m,1H),8.09(d,J＝8.2 Hz,1H),7.64–7.45(m,3H),7.39–7.22(m,17H),7.14(m,10H),6.95(dd,J＝9.5,3.3Hz,1H),6.91–6.72(m, 2H),5.46(d,J＝2.7Hz,1H),4.88(d,J＝11.3Hz,1H),4.64–4.38(m,6H),4.09(m,2H),3.99(s,1H),3.90– 3.72(m,5H),3.70–3.50(m,2H).

product 25:

¹H NMR(400MHz,Chloroform-d)9.54(s,1H),8.72–8.56(m,1H),8.45(d,J＝6.0Hz,1H),8.13(dd,J＝8.4, 1.7Hz,1H),7.73–6.86(m,45H),5.34(m,2H),4.72–4.19(m,16H),4.18–4.01(m,4H),3.94–3.73(m,8H), 3.67(s,3H).

¹³C NMR(101MHz,CDCl₃)157.49,148.03,140.33,138.49,138.46,138.36,138.31,136.03,133.96,132.29, 129.94,128.29,128.21,128.06,127.95,127.71,127.64,127.52,127.40,127.36,127.20,127.07,121.61,120.81, 113.21,77.36,77.24,77.04,76.72,76.54,75.42,75.02,73.22,72.57,72.35,71.93,68.93,55.60.

product 26:

¹H NMR(400MHz,Chloroform-d)9.68(s,1H),8.86(dd,J＝4.3,1.7Hz,1H),8.45(d,J＝7.3Hz,1H),8.19 (dd,J＝8.3,1.7Hz,1H),7.62–7.47(m,3H),7.26–7.16(m,2H),7.07(dd,J＝7.9,1.7Hz,1H),5.32(s,1H), 4.96(dd,J＝6.0,1.7Hz,1H),4.77(dd,J＝6.0,3.6Hz,1H),4.48(m,1H),4.29–4.11(m,2H),4.01(dd,J＝7.7, 3.6Hz,1H),2.39(s,3H),1.45(2s,6H),1.38(s,3H),1.25(s,3H).

¹³C NMR(101MHz,CDCl₃)148.25,148.00,138.98,138.41,136.28,134.36,128.50,127.32,126.52,125.71, 123.64,121.77,121.23,115.05,112.96,109.23,87.07,82.90,81.83,81.04,77.36,77.25,77.04,76.72,73.65, 67.05,26.95,26.44,25.25,25.01,21.14.

product 27:

¹H NMR(400MHz,Chloroform-d)9.63(s,1H),8.96–8.71(m,1H),8.46(d,J＝7.4Hz,1H),8.17(dd,J＝8.3, 1.6Hz,1H),7.79–7.64(m,5H),7.57–7.33(m,10H),7.18(s,1H),7.02(d,J＝8.0Hz,1H),5.19(d,J＝4.8Hz, 1H),4.69(dd,J＝6.8,4.4Hz,1H),4.61(dd,J＝6.8,4.8Hz,1H),4.15(q,J＝4.0Hz,1H),3.95(dd,J＝11.2,3.4 Hz,1H),3.85(dd,J＝11.3,4.2Hz,1H),2.38(s,3H),1.35(s,3H),1.19(s,3H),1.04(s,9H).

¹³C NMR(101MHz,CDCl₃)151.47,148.17,147.45,138.46,138.37,136.27,135.73,135.68,134.61,133.34, 129.81,129.74,129.72,128.05,127.73,127.37,126.56,126.23,122.98,121.70,120.95,114.97,114.29,86.84, 84.37,81.75,81.39,77.36,77.24,77.04,76.72,63.99,27.34,26.86,26.83,25.46,21.15,19.28.

product 28:

¹H NMR(400MHz,Chloroform-d)10.94(s,1H),9.03(d,J＝7.7Hz,1H),8.71(d,J＝4.1Hz,1H),8.14(d,J ＝8.3Hz,1H),7.63(t,J＝8.0Hz,1H),7.58–7.48(m,2H),7.40–7.26(m,10H),7.13(m,3H),7.02(dd,J＝9.0, 3.1Hz,1H),6.78(m,2H),5.79(d,J＝3.6Hz,1H),5.35(dd,J＝10.2,3.6Hz,1H),4.68(s,2H),4.20(d,J＝12.5 Hz,1H),4.14–4.07(m,1H),3.97(d,J＝12.4Hz,1H),3.84(s,3H),3.81–3.67(m,3H),3.58(d,J＝12.0Hz, 1H),1.80(s,3H).

¹³C NMR(101MHz,CDCl₃)170.46,164.36,155.22,149.14,148.07,138.79,138.14,136.65,134.99,128.38, 128.25,128.07,127.79,127.73,127.65,127.23,126.75,126.53,121.91,121.66,119.43,118.10,117.41,114.71, 98.90,77.35,77.03,76.71,75.50,73.70,71.96,71.70,70.60,61.94,55.84,29.71,20.68.

Claims

1. a synthetic method of aryl carbon glycoside compounds is characterized by comprising the following steps: stirring an amide raw material, a sugar donor, a divalent palladium metal catalyst, alkali and an organic solvent at a specified temperature for reaction, cooling to room temperature, directly filtering, spin-drying filtrate, and performing column chromatography separation to obtain the aryl carbon glycoside compound; the alkali is inorganic alkali;

the amide raw material is

Wherein Aux is

One of (1); ar is aromatic ring and aromatic heterocycle;

the sugar donor has a structural general formula

The general structural formula of the aryl carbon glycoside compound is as follows:

the reaction raw material for synthesizing the aryl carbon glycoside compound also comprises an additive; the additive is one of acetic acid, isoleucine protected by nitrogen acetyl, pivalic acid, 2-phenylbenzoic acid, dibenzyl phosphate, nitrogen-tert-butoxycarbonyl L-valine, nitrogen-tert-butoxycarbonyl L-proline or nitrogen-tert-butoxycarbonyl L-serine;

the divalent palladium metal catalyst is Pd (OAc)₂、PdCl₂、PdBr₂Or Pd (MeCN)₂Cl₂One kind of (1).

2. The method as claimed in claim 1, wherein the protecting group P in the sugar donor is one of acetyl, benzyl, methyl, t-butyl diphenyl, silyl, benzoyl, allyl, benzylidene acetal, ketal, and methyl ether.

3. The method of claim 1, wherein the inorganic base is one of potassium acetate, potassium carbonate, sodium bicarbonate, silver acetate, or silver carbonate.

4. Root of herbaceous plantThe method as claimed in claim 1, wherein the organic solvent is benzene-series solvent, dichloromethane, chloroform, tetrahydrofuran or CCl₄One kind of (1).

5. The method of claim 1, wherein the amide starting material is present in the solvent at a concentration of 0.001M to 5M; the molar ratio of the amide raw material, the sugar donor, the divalent palladium metal catalyst and the alkali is 1:1.2-3.0:0.05-1.0: 1.5-3.0.

6. The method of claim 1, wherein the molar ratio of the amide starting material to the additive is 1: 0.2-1.0.

7. The method of claim 1, wherein the stirring at the specified temperature is performed under the following conditions: the temperature interval is 25-110 ℃; the stirring time is 1-12 hours.