CN115433170A - Synthetic method of indole carbon glycoside compound - Google Patents

Abstract

The invention belongs to the field of compound synthesis, and particularly discloses a synthesis method of an indole carbon glycoside compound. The method comprises the following steps: adding the glucene, the o-alkynyl aniline, the palladium catalyst, the alkali and the additive into a clean reactor, then adding the organic solvent, stirring and reacting at room temperature, and carrying out post-treatment after the reaction is finished to obtain the indole carbon glycoside compound. Wherein the saccharide alkene is selected from one of glucose alkene, galactose alkene and rhamnosene. The synthesis method disclosed by the invention has the advantages of cheap and easily-obtained raw materials, economic reaction steps, good substrate universality, strong functional group compatibility, mild reaction conditions, capability of generating at room temperature, safety, simplicity and convenience in operation, no need of strict anhydrous anaerobic operation, and good industrial application prospect.

Description

Synthetic method of indole carbon glycoside compound

Technical Field

The invention belongs to the field of compound synthesis, and particularly relates to a synthesis method of an indole carbon glycoside compound.

Background

Indole carbon glycoside as one kind of carbohydrate compound with indole and glycosyl skeleton connected via carbon-carbon bond exists in natural products and protein with important biological function and may exhibit important physiological activity including human leukemia resisting cell HL-60 and human liver cancer resisting cell HepG2. In addition, some 3-indolyl glycoside compounds may be also used as glucose combined transport protein 2 (SGLT 2) inhibitor and have great application foreground in treating diabetes. Therefore, how to synthesize the indole carbon glycoside skeleton with high efficiency has been a hot topic of research by chemists.

The traditional strategy for constructing the indole carbon glycoside skeleton is mainly prepared by the reaction of lithium-indole with sugar lactone or epoxy sugar (for example, total Synthesis of Novel Subclases of Glyco-amino Acid Structure Motif: C2-alpha-l-C-manosyl-l-tryptophan. J. Am. Chem. Soc., 1999, 121, 9754 Stereocotrol synthesized of Heterocyclic C-nucleosides. J. Org. Chem., 2002, 67, 3724, etc. documents describe). However, these methods are harsh in conditions, require an organolithium reagent which is difficult to prepare and a stoichiometric accelerator, and are not environmentally friendly in preparation, and have long reaction steps and a narrow practical range of products.

In recent years, with the rapid development of metal organic chemistry, the coupling reaction catalyzed by transition metal provides a method for synthesizing indole carbon glycoside. The method mainly comprises the following steps: (1) The glycosyl donor containing the Terminal alkyne and 2-iodoaniline are used to construct 2-indolyl-C-glycosides by series Sonogashira/heterocycles (e.g., total Synthesis of indole-3-acetylnitrile-4-methoxy-2-C-. Beta. -d-glucopyranoside. Proposual for structural vision of the natural product. Org. Biom. Chem., 2012, 10, 5194 Synthesis of 1, 3-and 2,3-hydrolyzed compounds as Potential Trisaccharoide Synthesis, 2012, 44, 1385 Synthesis of degraded Mono-and Diindole C-nucleotide analogs from Sugar Terminal alkyl by sequence specific Sonogashira/hybridization reaction, J. Org. Chem., 2014, 79, 9490. (2) indole-C-Glycosides (e.g., as described in General Approach to Five-member Nitrogen Heteroaryl C-Glycosides Using a Palladium/coater coordinated C-H functioning Stratagene, org. Lett., 2017, 19, 3608) are constructed by C-H activation Using Palladium metal catalysis Using iodosylenes as glycosyl donors. (3) Indole carbon glycosides are constructed by introducing a targeting group Using a chloro glycoside as a glycosyl donor, and performing C-H activation of Indole by targeting function of the targeting group under metal catalysis (e.g., total Synthesis of C- α -manosyl Tryptophan via Palladium-Catalyzed C-H catalysis, CCS chem., 2021, 3, 1729 Pd-Catalyzed Ortho-Directed C-H catalysis of olefins Using N-linked Bidentate Automation. Chin. J. Chem. 2021, 39, one-dot Stereose Synthesis of 8978-polysaccharides and Trypton-C-glycosides via Pakisaldehyde-peptide C-H catalysis of 20281, published by published et al, 2022, and so on). Although some progress has been made, all of the above methods require the use of glycosyl donors which cannot be prepared simply and which require prior functionalization. Moreover, these methods require high reaction temperatures, such as those required for the methods (2) and (3), which are generally required to be at 100 ℃ or higher. Furthermore, the introduction of a directing group can have a major impact on both the step economy and atom economy of the reaction. These limitations greatly limit the application prospects of the reaction.

In recent years, some progress has been made in the research on the synthesis of indole carbon glycosides (e.g., palladium-catalyzed C-glycosylation and organization of o-alkylanilides with 1-iodocarbohydrates: compatible access to 3-alkenyl-C-glycosides, org. Biomol. Chem., 2020, 18, 8834; patent application published under CN 110684018A; patent application published under CN 110590830A). According to the method, iodosylene is used as a glycosyl donor, and is subjected to cyclization reaction with o-alkynyl aniline at 100 ℃ under the palladium catalysis condition to generate indole carbon glycoside. The main mechanism is that firstly, zero-valent palladium and iodosylene are subjected to oxidation addition to obtain an intermediate a, then a glycosyl palladium intermediate and o-alkynyl aniline are subjected to nucleophilic cyclization reaction to obtain a product c through an intermediate b, and finally the intermediate c is subjected to reduction elimination to obtain the 1,2 site unsaturated indole carbon glycoside compound (shown in figure 1). However, the use of iodosylenes, which are not readily prepared, and the high temperature heating and strict anhydrous oxygen-free operation required for the reaction all have an impact on the further use of the reaction. Therefore, the development of a method for synthesizing the indole carbon glycoside with mild conditions and simple and easily obtained raw materials has important scientific significance and application value.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a simple, convenient and efficient synthesis method of indole carbon glycoside.

The technical scheme of the invention is as follows:

a synthetic method of indole carbon glycoside compounds comprises the following steps: adding o-alkynyl aniline shown in a formula I, glycene shown in a formula II, a palladium catalyst, alkali and an additive into a clean reactor, then adding an organic solvent, stirring and reacting at room temperature, and carrying out post-treatment after the reaction is finished to obtain the indole carbon glycoside compound III, wherein the reaction formula is shown as follows:

wherein R is ¹ Selected from H, methyl, fluorine, chlorine or bromine; r ² Selected from phenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 3-methylphenyl or 3-fluorophenyl; r ³ Selected from p-toluenesulfonyl, benzenesulfonyl or p-nitrobenzenesulfonyl; p represents a protecting group for a hydroxyl group on a saccharide, selected from acetyl or benzoyl.

The glycylene shown in the formula II is selected from one of glucene, galactene and rhamnosene, and the molar ratio of the addition amount of the glycylene shown in the formula II to the compound I is (1~3): 1. Preferably, the glucene is triacetylglucene or tribenzoylglucene, the galactene is triacetylgalactene, and the rhamnosene is triacetylrhamnosene.

The palladium catalyst is one of palladium acetate and palladium iodide, and the addition amount of the palladium catalyst is 5-15% of the molar amount of the compound I.

The alkali is any one of cesium carbonate, potassium carbonate, sodium carbonate, potassium phosphate, potassium hydroxide and triethylamine, and the molar ratio of the added alkali to the compound I is (1~3): 1.

The additive is any one of potassium iodide, sodium iodide and tetrabutylammonium iodide, and the molar ratio of the additive to the compound I is (1~3): 1.

The organic solvent is any one of N, N-dimethylformamide and N, N-dimethylacetamide. Preferably, the organic solvent is N, N-dimethylformamide. The ratio of the addition amount of the organic solvent to the compound I is (0.5 to 2) mL: 1 mmol.

The reaction time of the above reaction is 5 to 10 hours.

The post-treatment is to extract the reaction liquid with ethyl acetate and water for three times, combine organic phases, dry the organic phases by using anhydrous sodium sulfate, filter the organic phases, evaporate the solvent under reduced pressure to obtain a crude product, and separate and purify the crude product by column chromatography to obtain the indole carbon glycoside compound.

Preferably, the column chromatography separation and purification uses a mixed solvent of petroleum ether and ethyl acetate as an eluent, and the volume ratio of the petroleum ether to the ethyl acetate is (2-10): 1. Preferably, the volume ratio of petroleum ether to ethyl acetate is 5:1.

The invention has the beneficial effects that: (1) The synthesis process is simple and efficient, the indole carbon glycoside compound can be synthesized with high selectivity through the tandem reaction of the glucene and the o-alkynyl aniline compound, the substrate universality is good, the reaction stereoselectivity is good, and the functional group compatibility is strong; (2) The raw materials are cheap and easy to obtain, wherein the glucene is a commercially available product and is low in price; (3) the reaction condition is mild, and the reaction can be carried out at room temperature; simple operation, no strict anhydrous and anaerobic operation, good yield maintenance and suitability for industrial production.

Drawings

FIG. 1 is a diagram of the reaction mechanism of the prior art.

FIG. 2 is a reaction scheme of example 1 of the present invention.

FIG. 3 is a hydrogen spectrum of the product obtained in example 1 of the present invention.

FIG. 4 is a carbon spectrum of the product obtained in example 1 of the present invention.

Detailed Description

The present invention will be described in further detail with reference to examples and drawings, but the embodiments of the present invention are not limited thereto.

Example 1

0.2 mmol of N- [2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, the solvent is evaporated under reduced pressure to obtain a crude product, and then the crude product is separated and purified by column chromatography (in the embodiment, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product, wherein the yield is 75%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (d, J = 8.5 Hz, 1H), 7.93 (dd, J = 8.0, 1.2 Hz, 1H), 7.52 – 7.22 (m, 9H), 7.09 (d, J = 8.1 Hz, 2H), 5.99 – 5.86 (m, 2H), 5.10 – 5.04 (m, 1H), 4.99 (q, J = 1.9 Hz, 1H), 4.23 – 4.13 (m, 2H), 4.09 – 4.01 (m, 1H), 2.32 (s, 3H), 2.16 (s, 3H), 1.97 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.51, 170.47, 144.83, 139.44, 137.05, 135.56, 133.51, 130.07, 129.45, 129.29, 128.64, 127.44, 126.91, 125.06, 123.74, 122.12, 120.99, 119.59, 115.56, 72.45, 65.84, 64.24, 61.71, 21.57, 21.10, 20.71; HRMS (ESI) m/z calcd for C ₃₁ H ₂₉ NO ₇ SH [M + H] ⁺ : 560.1729; Found: 560.1737.

example 2

0.2 mmol of N- [2- [ (4-methylphenyl) ethynyl ] phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide are added to a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted three times with ethyl acetate, the organic phases are combined, dried with anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product with a yield of 66%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.42 – 7.31 (m, 3H), 7.31 – 7.17 (m, 5H), 7.09 (d, J = 7.9 Hz, 2H), 5.96 (ddd, J = 10.4, 4.3, 2.0 Hz, 1H), 5.91 (dd, J= 10.5, 1.8 Hz, 1H), 5.08 (dt, J = 4.8, 2.5 Hz, 1H), 4.98 (q, J = 2.1 Hz, 1H), 4.26 – 4.12 (m, 2H), 4.06 (dd, J = 11.2, 5.0 Hz, 1H), 2.46 (s, 3H), 2.32 (s, 3H), 2.17 (s, 3H), 2.00 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.64, 170.56, 144.81, 139.71, 139.28, 136.95, 135.40, 133.66, 129.43, 128.71, 128.25, 127.01, 126.92, 124.95, 123.74, 121.96, 120.90, 119.40, 115.59, 72.43, 65.88, 64.22, 61.74, 21.62, 21.58, 21.17, 21.15, 20.78, 20.76; HRMS (ESI) m/z calcd for C ₃₂ H ₃₁ NO ₇ SH [M + H] ⁺ : 574.1885; Found: 574.1894.

example 3

0.2 mmol of N- [2- [ (4-methoxyphenyl) ethynyl ] phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide were added to a reaction tube, and the reaction was stirred at room temperature for 6 hours to terminate the reaction, then 5 ml of water was added, the reaction solution was extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure to give a crude product, which was then separated and purified by column chromatography (in this example, the eluent was a mixed solvent of petroleum ether and ethyl acetate at a volume ratio of 5:1) to give the desired product in a yield of 73%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.35 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 7.6 Hz, 1H), 7.42 – 7.22 (m, 6H), 7.09 (d, J = 8.2 Hz, 2H), 6.94 (d, J = 8.3 Hz, 2H), 5.96 (ddd, J = 10.4, 4.2, 2.0 Hz, 1H), 5.91 (dd, J = 10.4, 1.8 Hz, 1H), 5.09 (dt, J = 4.4, 2.5 Hz, 1H), 4.99 (q, J = 2.1 Hz, 1H), 4.26 – 4.12 (m, 2H), 4.12 – 4.01 (m, 1H), 3.89 (s, 3H), 2.32 (s, 3H), 2.17 (s, 3H), 2.00 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.58, 170.51, 160.33, 144.77, 139.56, 136.99, 135.58, 133.55, 129.42, 128.71, 126.90, 124.91, 123.71, 122.11, 122.00, 120.83, 119.35, 115.61, 112.90, 72.37, 66.00, 64.29, 61.80, 55.31, 21.58, 21.12, 20.75; HRMS (ESI) m/z calcd for C ₃₂ H ₃₁ NO ₈ SH [M + H] ⁺ : 590.1738; Found: 590.1765.

example 4

0.2 mmol of N- [2- [ (4-tert-butylphenyl) ethynyl ] phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide were added to a reaction tube, and the reaction was stirred at room temperature for 6 hours to terminate the reaction, and then 5 ml of water was added, and the reaction solution was extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure to give a crude product, which was then separated and purified by column chromatography (in this example, the eluent was a mixed solvent of petroleum ether and ethyl acetate at a volume ratio of 5:1) to give the desired product in a yield of 69%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 7.3 Hz, 1H), 7.46 – 7.32 (m, 3H), 7.34 – 7.22 (m, 5H), 7.07 (d, J = 8.2 Hz, 2H), 6.03 – 5.84 (m, 2H), 5.12 – 5.07 (m, 1H), 4.98 (q, J = 1.8 Hz, 1H), 4.24 – 4.13 (m, 2H), 4.10 – 3.99 (m, 1H), 2.32 (s, 3H), 2.17 (s, 3H), 1.99 (s, 3H), 1.40 (s, 9H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.59, 170.55, 152.28, 144.71, 139.78, 137.07, 135.46, 133.59, 129.38, 128.69, 127.00, 126.85, 124.92, 124.36, 123.68, 122.10, 120.88, 119.32, 115.61, 72.29, 66.01, 64.29, 61.87, 34.84, 31.39, 21.61, 21.16, 20.79; HRMS (ESI) m/zcalcd for C ₃₅ H ₃₇ NO ₇ SH [M + H] ⁺ : 616.2358; Found: 616.2363.

example 5

0.2 mmol of N- [2- [ (4-chlorophenyl) ethynyl ] phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide were added to a reaction tube, and the reaction was stirred at room temperature for 6 hours to terminate the reaction, then 5 ml of water was added, the reaction solution was extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure to give a crude product, which was then separated and purified by column chromatography (in this example, the eluent was a mixed solvent of petroleum ether and ethyl acetate at a volume ratio of 5:1) to give the desired product in 55% yield. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.45 – 7.36 (m, 3H), 7.37 – 7.24 (m, 5H), 7.11 (d, J = 8.1 Hz, 2H), 5.97 (ddd, J = 10.3, 4.3, 2.2 Hz, 1H), 5.90 (dd, J= 10.3, 1.4 Hz, 1H), 5.09 (dt, J = 4.8, 2.4 Hz, 1H), 4.97 (q, J = 2.1 Hz, 1H), 4.25 – 4.13 (m, 2H), 4.11 – 4.00 (m, 1H), 2.33 (s, 3H), 2.16 (s, 3H), 2.00 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.57, 170.50, 145.09, 138.17, 137.04, 135.55, 135.30, 133.13, 129.56, 128.59, 128.52, 127.81, 126.83, 125.34, 123.93, 122.47, 121.00, 120.00, 115.61, 72.41, 65.75, 64.15, 61.63, 21.63, 21.14, 20.76; HRMS (ESI) m/z calcd for C ₃₁ H ₂₈ ClNO ₇ SH [M + H] ⁺ : 594.1340; Found: 594.1348.

example 6

0.2 mmol of N- [2- [ (3-methylphenyl) ethynyl ] phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide are added to a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted three times with ethyl acetate, the organic phases are combined, dried with anhydrous sodium sulfate, filtered, the solvent is evaporated under reduced pressure to obtain a crude product, and then the crude product is separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product with a yield of 71%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 7.9 Hz, 1H), 7.43 – 7.22 (m, 6H), 7.10 (d, J = 8.1 Hz, 4H), 6.03 – 5.83 (m, 2H), 5.08 (dt, J = 4.3, 2.5 Hz, 1H), 5.00 (q, 1H), 4.26 – 4.13 (m, 2H), 4.06 (td, J = 10.0, 8.9, 2.6 Hz, 1H), 2.39 (s, 3H), 2.33 (s, 3H), 2.17 (s, 3H), 1.99 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.55, 144.80, 137.00, 135.60, 133.59, 129.84, 129.40, 128.58, 127.35, 126.99, 124.99, 123.68, 121.97, 120.94, 119.30, 115.51, 65.90, 64.25, 61.73, 21.60, 21.47, 21.15, 20.75; HRMS (ESI) m/z calcd for C ₃₂ H ₃₁ NO ₇ SH [M + H] ⁺ : 574.1887; Found: 574.1894.

example 7

0.2 mmol of N- [ 4-methyl-2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product with a yield of 63%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.21 (d, J = 8.6 Hz, 1H), 7.74 – 7.68 (m, 1H), 7.53 – 7.44 (m, 1H), 7.42 (t, J = 7.2 Hz, 2H), 7.38 – 7.28 (m, 4H), 7.20 (dd, J = 8.5, 1.8 Hz, 1H), 7.08 (d, J = 8.1 Hz, 2H), 5.96 (ddd, J = 10.2, 4.8, 2.2 Hz, 1H), 5.89 (dd, J = 10.4, 1.8 Hz, 1H), 5.07 (dt, J = 4.8, 2.3 Hz, 1H), 4.96 (q, J = 2.1 Hz, 1H), 4.25 (td, J = 6.3, 5.1, 2.4 Hz, 1H), 4.23 – 4.13 (m, 1H), 4.05 (dd, J = 11.5, 5.2 Hz, 1H), 2.43 (s, 3H), 2.32 (s, 3H), 2.18 (s, 3H), 1.99 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.56, 170.50, 144.75, 139.36, 135.40, 135.26, 133.90, 133.30, 130.13, 129.42, 129.26, 128.78, 127.46, 126.90, 126.47, 121.62, 120.86, 119.39, 115.28, 72.61, 65.65, 64.12, 61.53, 21.60, 21.16, 20.75; HRMS (ESI) m/z calcd for C ₃₂ H ₃₁ NO ₇ SH [M + H] ⁺ : 574.1888; Found: 574.1894.

example 8

0.2 mmol of N- [ 4-bromo-2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide are added to a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted three times with ethyl acetate, the organic phases are combined, dried with anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product with a yield of 57%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.22 (d, J = 9.0 Hz, 1H), 8.14 (d, J = 2.0 Hz, 1H), 7.56 – 7.37 (m, 4H), 7.37 – 7.24 (m, 4H), 7.11 (d, J = 8.2 Hz, 2H), 6.02 (ddd, J = 10.4, 5.3, 2.3 Hz, 1H), 5.86 (dd, J= 10.3, 1.8 Hz, 1H), 5.04 (dt, J = 5.4, 2.0 Hz, 1H), 4.93 (q, J = 2.1 Hz, 1H), 4.32 – 4.23 (m, 1H), 4.19 (dd, J = 11.5, 7.8 Hz, 1H), 4.04 (dd, J = 11.5, 5.4 Hz, 1H), 2.34 (s, 3H), 2.27 (s, 3H), 1.99 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.75, 170.50, 145.21, 140.00, 135.76, 135.19, 133.67, 130.03, 129.60, 129.59, 129.41, 127.91, 127.62, 126.92, 123.89, 121.55, 118.84, 117.34, 116.94, 72.93, 65.26, 63.72, 61.24, 21.65, 21.31, 20.73; HRMS (ESI) m/z calcd for C ₃₁ H ₂₈ BrNO ₇ SH [M + H] ⁺ : 638.0658; Found: 638.0677.

example 9

0.2 mmol of N- [ 4-chloro-2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product with a yield of 55%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.27 (d, J = 9.0 Hz, 1H), 8.01 (d, J = 2.2 Hz, 1H), 7.55 – 7.46 (m, 1H), 7.43 (s, 2H), 7.38 – 7.24 (m, 5H), 7.10 (d, J = 8.1 Hz, 2H), 6.02 (ddd, J = 10.4, 5.3, 2.3 Hz, 1H), 5.86 (dd, J = 10.4, 1.9 Hz, 1H), 5.04 (dd, J = 5.2, 2.2 Hz, 1H), 4.94 (q, J = 2.1 Hz, 1H), 4.28 (td, J = 6.6, 5.6, 1.5 Hz, 1H), 4.24 – 4.14 (m, 1H), 4.04 (dd, J = 11.6, 5.5 Hz, 1H), 2.34 (s, 3H), 2.25 (s, 3H), 1.99 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.69, 170.50, 145.18, 140.16, 135.39, 135.19, 133.67, 129.58, 129.46, 127.62, 126.92, 125.23, 121.55, 120.87, 118.99, 116.59, 72.92, 65.32, 63.77, 61.26, 21.64, 21.16, 20.73; HRMS (ESI) m/z calcd for C ₃₁ H ₂₈ ClNO ₇ SH [M + H] ⁺ : 594.1342; Found: 594.1348.

example 10

0.2 mmol of N- [ 5-methyl-2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product with a yield of 67%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.16 (s, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.51 – 7.42 (m, 1H), 7.40 (t, J = 7.4 Hz, 2H), 7.36 – 7.27 (m, 4H), 7.15 – 7.05 (m, 3H), 5.94 (ddd, J = 10.3, 4.2, 2.0 Hz, 1H), 5.89 (dd, J = 10.4, 1.8 Hz, 1H), 5.07 (dt, J = 4.1, 2.5 Hz, 1H), 4.95 (q, J = 2.0 Hz, 1H), 4.25 – 4.11 (m, 2H), 4.10 – 3.95 (m, 1H), 2.53 (s, 3H), 2.33 (s, 3H), 2.16 (s, 3H), 1.99 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.60, 170.53, 144.76, 138.78, 137.48, 135.57, 135.18, 133.54, 130.18, 129.44, 129.19, 127.42, 126.88, 126.40, 125.27, 122.09, 120.54, 119.55, 115.65, 72.32, 65.90, 64.25, 61.73, 22.14, 21.61, 21.15, 20.77; HRMS (ESI) m/z calcd for C ₃₂ H ₃₁ NO ₇ SH [M + H] ⁺ : 574.1888; Found: 574.1894.

example 11

0.2 mmol of N- [2- (phenylethynyl) phenyl ] -benzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide are added to a reaction tube, and the reaction is stopped by stirring at room temperature for 6 hours, then 5 ml of water is added, the reaction solution is extracted three times with ethyl acetate, the organic phases are combined, dried with anhydrous sodium sulfate, filtered, the solvent is evaporated under reduced pressure to obtain a crude product, and then the crude product is separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 8978 zx8978) to obtain the target product with a yield of 79%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.36 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 7.7 Hz, 1H), 7.52 – 7.37 (m, 7H), 7.36 – 7.26 (m, 5H), 5.96 (ddd, J = 10.4, 4.3, 2.0 Hz, 1H), 5.90 (dd, J = 10.4, 1.8 Hz, 1H), 5.07 (dt, J = 4.7, 2.5 Hz, 1H), 4.98 (q, J = 2.1 Hz, 1H), 4.24 – 4.13 (m, 2H), 4.04 (dd, J = 10.5, 3.9 Hz, 1H), 2.17 (s, 3H), 1.98 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.59, 170.54, 139.36, 138.36, 137.05, 133.80, 133.48, 129.88, 129.38, 128.88, 128.60, 127.51, 126.88, 125.20, 123.89, 122.11, 121.03, 119.72, 115.55, 72.46, 65.76, 64.17, 61.63, 21.16, 20.79; HRMS (ESI) m/zcalcd for C ₃₀ H ₂₇ NO ₇ SH [M + H] ⁺ : 546.1570; Found: 546.1581.

example 12

0.2 mmol of N- [2- (phenylethynyl) phenyl ] -4-nitrobenzenesulfonamide, 0.4 mmol of triacetylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate for three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, the solvent is evaporated under reduced pressure to obtain a crude product, and then the crude product is separated and purified by column chromatography (in the embodiment, the eluent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 5:1) to obtain the target product, wherein the yield is 51%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.33 (d, J = 8.5 Hz, 1H), 8.17 – 8.12 (m, 2H), 7.96 (d, J = 7.6 Hz, 1H), 7.65 – 7.58 (m, 2H), 7.57 – 7.28 (m, 7H), 5.97 (ddd, J = 10.4, 4.6, 2.2 Hz, 1H), 5.88 (dd, J = 10.3, 1.3 Hz, 1H), 5.05 (dt, J = 4.3, 2.1 Hz, 1H), 5.01 (q, J = 2.1 Hz, 1H), 4.26 – 4.14 (m, 2H), 4.05 (dd, J = 10.5, 3.9 Hz, 1H), 2.17 (s, 3H), 1.99 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.51, 170.47, 150.49, 143.31, 138.95, 136.86, 133.18, 129.79, 129.40, 128.80, 128.22, 127.78, 125.74, 124.57, 124.11, 122.21, 121.48, 120.98, 115.48, 72.68, 65.52, 64.03, 61.47, 21.14, 20.76; HRMS (ESI) m/z calcd for C ₃₀ H ₂₆ N ₂ O ₉ SH [M + H] ⁺ : 591.1424; Found: 591.1432.

example 13

0.2 mmol of N- [2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of tribenzoylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, the solvent is evaporated under reduced pressure to obtain a crude product, and then the crude product is separated and purified by column chromatography (in the embodiment, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product, wherein the yield is 46%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (d, J = 8.5 Hz, 1H), 8.20 – 8.13 (m, 2H), 8.09 (d, J = 7.5 Hz, 1H), 7.99 – 7.89 (m, 2H), 7.66 – 7.55 (m, 2H), 7.50 (t, J = 7.7 Hz, 2H), 7.45 – 7.23 (m, 10H), 7.18 (t, J = 7.8 Hz, 1H), 7.06 (d, J = 8.1 Hz, 2H), 6.11 (ddd, J = 10.4, 4.9, 2.2 Hz, 1H), 5.98 (dd, J = 10.4, 1.9 Hz, 1H), 5.42 (dt, J = 4.7, 2.2 Hz, 1H), 5.14 (q, J = 2.2 Hz, 1H), 4.62 – 4.54 (m, 1H), 4.55 – 4.45 (m, 1H), 4.37 (dd, J = 11.5, 4.8 Hz, 1H), 2.30 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.05, 165.98, 144.81, 139.19, 137.07, 135.54, 134.23, 133.43, 133.20, 129.93, 129.81, 129.80, 129.75, 129.61, 129.44, 129.25, 128.56, 128.53, 128.37, 127.44, 126.91, 125.13, 123.73, 121.77, 121.12, 119.62, 115.58, 73.00, 65.79, 64.76, 62.27, 21.59; HRMS (ESI) m/z calcd for C ₄₁ H ₃₃ NO ₇ SH [M + H] ⁺ : 684.2044; Found: 684.2050.

example 14

0.2 mmol of N- [ 5-methyl-2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of tribenzoylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product with a yield of 61%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.21 – 8.11 (m, 3H), 7.98 – 7.88 (m, 3H), 7.63 (t, J = 7.4 Hz, 1H), 7.58 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.7 Hz, 2H), 7.46 – 7.27 (m, 8H), 7.06 (d, J = 8.1 Hz, 3H), 7.01 (d, J = 8.0 Hz, 1H), 6.09 (ddd, J = 10.4, 4.8, 2.2 Hz, 1H), 5.96 (dd, J = 10.4, 1.9 Hz, 1H), 5.42 (dt, J = 4.8, 2.3 Hz, 1H), 5.11 (q, J = 2.2 Hz, 1H), 4.58 – 4.53 (m, 1H), 4.53 – 4.44 (m, 1H), 4.37 (dd, J = 11.5, 4.7 Hz, 1H), 2.52 (s, 3H), 2.31 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.97, 144.68, 138.54, 137.56, 135.69, 135.21, 134.16, 133.40, 133.15, 130.09, 129.85, 129.79, 129.74, 129.64, 129.41, 129.12, 128.55, 128.34, 127.37, 126.86, 126.33, 125.21, 121.84, 120.66, 119.64, 115.67, 72.83, 65.93, 64.87, 62.40, 22.16, 21.58; HRMS (ESI) m/z calcd for C ₄₂ H ₃₅ NO ₇ SH [M + H] ⁺ : 698.2196; Found: 698.2207.

example 15

0.2 mmol of N- [2- (phenylethynyl) phenyl ] -benzenesulfonamide, 0.4 mmol of tribenzoylglucene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide are added into a reaction tube, and the reaction is stopped by stirring at room temperature for 6 hours, then 5 ml of water is added, the reaction solution is extracted three times with ethyl acetate, the organic phases are combined, dried with anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product with a yield of 53%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.35 (d, J = 8.5 Hz, 1H), 8.20 – 8.13 (m, 2H), 8.10 (d, J = 7.6 Hz, 1H), 7.98 – 7.90 (m, 2H), 7.67 – 7.55 (m, 2H), 7.53 – 7.35 (m, 10H), 7.34 – 7.05 (m, 6H), 6.12 (ddd, J= 10.3, 4.9, 2.2 Hz, 1H), 5.97 (dd, J = 10.3, 1.9 Hz, 1H), 5.41 (dt, J = 4.7, 2.2 Hz, 1H), 5.14 (q, J = 2.2 Hz, 1H), 4.63 – 4.55 (m, 1H), 4.55 – 4.46 (m, 1H), 4.37 (dd, J = 11.6, 4.8 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.03, 165.97, 139.14, 138.50, 137.16, 134.14, 133.72, 133.43, 133.20, 129.82, 129.80, 129.78, 129.74, 129.61, 129.30, 128.84, 128.56, 128.53, 128.38, 127.47, 126.86, 125.23, 123.83, 121.85, 121.19, 119.81, 115.56, 77.39, 77.07, 76.75, 73.00, 65.78, 64.76, 62.27, 31.61, 22.68, 14.17; HRMS (ESI) m/z calcd for C ₄₀ H ₃₁ NO ₇ SH [M + H] ⁺ : 670.1887; Found: 670.1894.

example 16

0.2 mmol of N- [2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylgalactan, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, the reaction is stirred at room temperature for 6 hours to stop, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate for three times, the organic phases are combined and dried by using anhydrous sodium sulfate, filtered, the solvent is evaporated under reduced pressure to obtain a crude product, and then the crude product is separated and purified by column chromatography (in the embodiment, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product, wherein the yield is 79%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.35 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.46 (t, J = 7.3 Hz, 1H), 7.42 – 7.24 (m, 8H), 7.11 (d, J = 8.1 Hz, 2H), 5.94 – 5.89 (m, 1H), 5.86 (ddd, J = 10.3, 4.0, 2.1 Hz, 1H), 5.28 (t, J = 3.7 Hz, 1H), 5.18 (dd, J = 2.7, 1.4 Hz, 1H), 4.25 – 4.15 (m, 1H), 4.15 – 4.06 (m, 2H), 2.33 (s, 3H), 2.07 (s, 3H), 1.85 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.53, 170.45, 144.85, 139.97, 136.80, 135.69, 132.79, 130.23, 129.46, 129.30, 129.17, 127.30, 126.89, 125.05, 123.89, 122.92, 120.57, 119.15, 115.54, 69.62, 67.27, 64.32, 61.70, 21.59, 20.95, 20.64; HRMS (ESI) m/z calcd for C ₃₁ H ₂₉ NO ₇ SH [M + H] ⁺ : 560.1734; Found: 560.1737.

example 17

0.2 mmol of N- [2- [ (4-methylphenyl) ethynyl ] phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylgalactene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, the solvent is evaporated under reduced pressure to obtain a crude product, and then the crude product is separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate with a volume ratio of 5:1) to obtain the target product with a yield of 79%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.43 – 7.32 (m, 3H), 7.32 – 7.23 (m, 1H), 7.20 (s, 4H), 7.11 (d, J = 8.1 Hz, 2H), 5.98 – 5.83 (m, 2H), 5.29 (t, J = 3.6 Hz, 1H), 5.19 – 5.13 (m, 1H), 4.23 – 4.15 (m, 1H), 4.14 – 4.05 (m, 2H), 2.44 (s, 3H), 2.33 (s, 3H), 2.07 (s, 3H), 1.86 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.60, 170.53, 144.80, 140.30, 139.28, 136.73, 135.61, 132.92, 129.43, 129.27, 128.08, 127.19, 126.89, 124.92, 123.86, 122.87, 120.51, 119.01, 115.56, 69.58, 67.35, 64.34, 61.76, 21.61, 21.59, 20.99, 20.66; HRMS (ESI) m/ z calcd for C ₃₂ H ₃₁ NO ₇ SH [M + H] ⁺ : 574.1889; Found: 574.1894.

example 18

0.2 mmol of N- [2- [ (4-methoxyphenyl) ethynyl ] phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylgalactan, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide were added to a reaction tube, and the reaction was stirred at room temperature for 6 hours to terminate the reaction, and then 5 ml of water was added, the reaction solution was extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure to give a crude product, which was then separated and purified by column chromatography (in this example, the eluent was a mixed solvent of petroleum ether and ethyl acetate at a volume ratio of 5:1) to give the desired product in a yield of 71%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.35 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 7.6 Hz, 1H), 7.43 – 7.30 (m, 3H), 7.32 – 7.23 (m, 1H), 7.22 (s, 2H), 7.11 (d, J = 8.1 Hz, 2H), 6.91 (d, J = 8.1 Hz, 2H), 5.98 – 5.85 (m, 2H), 5.28 (t, J = 3.4 Hz, 1H), 5.20 – 5.14 (m, 1H), 4.23 – 4.14 (m, 1H), 4.17 – 4.04 (m, 2H), 3.89 (s, 3H), 2.33 (s, 3H), 2.08 (s, 3H), 1.86 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.58, 170.52, 160.32, 144.80, 140.13, 136.77, 135.69, 132.99, 129.43, 129.26, 126.87, 124.91, 123.86, 122.81, 122.17, 120.45, 119.00, 115.60, 112.75, 69.59, 67.46, 64.30, 61.80, 55.33, 21.61, 20.99, 20.68; HRMS (ESI) m/z calcd for C ₃₂ H ₃₁ NO ₈ SH [M + H] ⁺ : 590.1837; Found: 590.1843

example 19

0.2 mmol of N- [2- [ (4-chlorophenyl) ethynyl ] phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetyl galactan, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide were added to a reaction tube, and the reaction was stirred at room temperature for 6 hours to terminate the reaction, then 5 ml of water was added, the reaction solution was extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure to give a crude product, which was then separated and purified by column chromatography (in this example, the eluent was a mixed solvent of petroleum ether and ethyl acetate at a volume ratio of 5:1) to give the desired product in a yield of 67%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (d, J = 8.5 Hz, 1H), 7.73 (d, J = 7.7 Hz, 1H), 7.44 – 7.23 (m, 8H), 7.13 (d, J = 8.1 Hz, 2H), 6.02 – 5.89 (m, 2H), 5.33 – 5.26 (m, 1H), 5.13 (s, 1H), 4.20 – 4.14 (m, 1H), 4.14 – 4.06 (m, 2H), 2.34 (s, 3H), 2.08 (s, 3H), 1.87 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.53, 170.50, 145.10, 138.78, 136.84, 135.57, 135.44, 132.67, 129.57, 129.12, 128.68, 127.68, 126.79, 125.31, 124.08, 123.29, 120.65, 119.62, 115.61, 69.70, 67.18, 64.16, 61.70, 21.64, 20.98, 20.66; HRMS (ESI) m/z calcd for C ₃₁ H ₂₈ ClNO ₇ SH [M + H] ⁺ : 594.1340; Found: 594.1348.

example 20

0.2 mmol of N- [2- [ (3-methylphenyl) ethynyl ] phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylgalactene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, the solvent is evaporated under reduced pressure to obtain a crude product, and then the crude product is separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate with a volume ratio of 5:1) to obtain the target product with a yield of 81%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.35 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 7.9 Hz, 1H), 7.43 – 7.24 (m, 6H), 7.11 (d, J = 8.1 Hz, 3H), 7.00 (d, J = 28.1 Hz, 1H), 5.97 – 5.81 (m, 2H), 5.28 (t, 1H), 5.21 – 5.13 (m, 1H), 4.25 – 4.16 (m, 1H), 4.15 – 4.06 (m, 2H), 2.40 – 2.31 (m, 6H), 2.07 (s, 3H), 1.86 (d, J = 11.8 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.53, 170.46, 144.78, 136.80, 132.90, 130.02, 129.39, 126.97, 124.95, 123.80, 122.82, 120.52, 115.49, 69.62, 67.31, 64.36, 61.74, 21.58, 21.42, 20.96, 20.64; HRMS (ESI) m/z calcd for C ₃₂ H ₃₁ NO ₇ SH [M + H] ⁺ : 574.1887; Found: 574.1894.

example 21

0.2 mmol of N- [ 4-bromo-2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylgalactan, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product with a yield of 65%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.23 (d, J = 8.9 Hz, 1H), 7.85 (d, J = 1.9 Hz, 1H), 7.52 – 7.43 (m, 2H), 7.38 (t, J = 7.6 Hz, 2H), 7.34 – 7.20 (m, 4H), 7.13 (d, J = 8.1 Hz, 2H), 5.88 – 5.82 (m, 2H), 5.27 – 5.21 (m, 1H), 5.17 – 5.15 (m, 1H), 4.21 – 4.01 (m, 3H), 2.35 (s, 3H), 2.07 (s, 3H), 1.89 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.61, 170.44, 145.22, 141.01, 135.46, 135.38, 132.28, 130.88, 129.69, 129.59, 127.94, 126.89, 123.20, 118.39, 117.35, 116.95, 69.56, 67.10, 64.15, 61.73, 21.67, 20.96, 20.66; HRMS (ESI) m/z calcd for C ₃₁ H ₂₈ BrNO ₇ SH [M + H] ⁺ : 638.0834; Found: 638.0843.

example 22

0.2 mmol of N- [ 5-methyl-2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetyl galactan, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product with a yield of 88%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.17 (s, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.50 – 7.40 (m, 1H), 7.42 – 7.25 (m, 6H), 7.11 (d, J = 8.1 Hz, 3H), 5.97 – 5.84 (m, 2H), 5.28 (td, J = 3.7, 1.3 Hz, 1H), 5.14 – 5.11 (m, 1H), 4.22 – 4.16 (m, 1H), 4.15 – 4.05 (m, 2H), 2.53 (s, 3H), 2.33 (s, 3H), 2.07 (s, 3H), 1.87 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.52, 170.47, 144.74, 139.41, 137.29, 135.78, 135.17, 132.97, 130.35, 129.43, 129.17, 127.27, 126.98, 126.85, 125.36, 122.87, 120.14, 119.12, 115.65, 69.59, 67.34, 64.29, 61.75, 22.08, 21.59, 20.95, 20.65; HRMS (ESI) m/z calcd for C ₃₂ H ₃₁ NO ₇ SH [M + H] ⁺ : 574.1891; Found: 574.1894.

example 23

0.2 mmol of N- [2- (phenylethynyl) phenyl ] -benzenesulfonamide, 0.4 mmol of triacetylgalactan, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide are added to a reaction tube, and the reaction is stopped by stirring at room temperature for 6 hours, then 5 ml of water is added, the reaction solution is extracted three times with ethyl acetate, the organic phases are combined, dried with anhydrous sodium sulfate, filtered, the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate at a volume ratio of 8978 zx8978) to obtain the target product with a yield of 87 ft. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.36 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 7.9 Hz, 1H), 7.52 – 7.41 (m, 4H), 7.41 – 7.27 (m, 8H), 5.95 – 5.81 (m, 2H), 5.28 (t, J = 3.6 Hz, 1H), 5.20 – 5.15 (m, 1H), 4.23 – 4.15 (m, 1H), 4.15 – 4.05 (m, 2H), 2.07 (s, 3H), 1.85 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.54, 170.44, 138.61, 136.88, 133.76, 132.71, 130.08, 129.35, 129.16, 128.87, 127.34, 126.83, 125.16, 124.00, 122.96, 120.63, 119.34, 115.54, 69.62, 67.25, 64.29, 61.70, 20.95, 20.67; HRMS (ESI) m/z calcd for C ₃₀ H ₂₇ NO ₇ SH [M + H] ⁺ : 546.1579; Found: 546.1581.

example 24

0.2 mmol of N- [2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylrhamnosene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, the reaction is stirred at room temperature for 6 hours to stop, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate for three times, the organic phases are combined and dried by using anhydrous sodium sulfate, filtered, the solvent is evaporated under reduced pressure to obtain a crude product, and the crude product is separated and purified by column chromatography (in the embodiment, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product, wherein the yield is 75%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (d, J = 8.4 Hz, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.54 – 7.22 (m, 9H), 7.07 (d, J = 8.2 Hz, 2H), 5.99 – 5.86 (m, 2H), 4.92 (q, J = 1.8 Hz, 1H), 4.87 (dt, J = 4.4, 2.1 Hz, 1H), 4.18 (qd, J = 6.7, 2.0 Hz, 1H), 2.30 (s, 3H), 2.17 (s, 3H), 1.18 (d, J = 6.8 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.84, 144.81, 139.14, 137.10, 135.31, 134.04, 130.24, 129.43, 129.20, 128.87, 127.46, 126.91, 125.03, 123.83, 121.41, 121.14, 120.30, 115.62, 71.27, 68.10, 64.27, 21.60, 21.30, 15.67; HRMS (ESI) m/z calcd for C ₂₉ H ₂₇ NO ₅ SH [M + H] ⁺ : 502.1678; Found: 502.1683.

example 25

0.2 mmol of N- [2- [ (4-tert-butylphenyl) ethynyl ] phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylrhamnosene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide, and 2 ml of N, N-dimethylformamide are added to a reaction tube, and the reaction is stirred at room temperature for 6 hours to terminate the reaction, then 5 ml of water is added, the reaction solution is extracted three times with ethyl acetate, the organic phases are combined, dried with anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate at a volume ratio of 5:1) to obtain the target product with a yield of 71%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.33 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.47 – 7.21 (m, 8H), 7.05 (d, J = 8.0 Hz, 2H), 5.98 – 5.86 (m, 2H), 4.97 – 4.92 (m, 1H), 4.91 – 4.85 (m, 1H), 4.17 (qd, J = 6.6, 2.3 Hz, 1H), 2.31 (s, 3H), 2.17 (s, 3H), 1.40 (s, 9H), 1.19 (d, J = 6.8 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.86, 152.15, 144.61, 139.48, 137.17, 135.34, 134.10, 129.32, 128.94, 127.03, 126.98, 124.83, 124.31, 123.71, 121.45, 121.03, 120.04, 115.65, 71.12, 68.26, 64.47, 34.84, 31.39, 21.58, 21.28, 15.83; HRMS (ESI) m/z calcd for C ₃₃ H ₃₅ NO ₅ SH [M + H] ⁺ : 558.2307; Found: 558.2309.

example 26

0.2 mmol of N- [2- [ (4-chlorophenyl) ethynyl ] phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylrhamnosene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted three times with ethyl acetate, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, the solvent is evaporated under reduced pressure to obtain a crude product, and then the crude product is separated and purified by column chromatography (in the embodiment, the eluent is a mixed solvent of petroleum ether and ethyl acetate with a volume ratio of 5:1) to obtain the target product with a yield of 60%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.33 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 7.9 Hz, 1H), 7.47 – 7.21 (m, 8H), 7.09 (d, J = 8.1 Hz, 2H), 6.00 – 5.93 (m, 1H), 5.88 (dd, J = 10.4, 1.4 Hz, 1H), 4.92 – 4.83 (m, 2H), 4.17 (q, J = 6.9 Hz, 1H), 2.32 (s, 3H), 2.16 (s, 3H), 1.19 (d, J = 6.8 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.79, 145.01, 137.81, 137.15, 135.40, 135.18, 133.66, 129.51, 128.79, 128.72, 127.80, 126.82, 125.28, 123.96, 121.72, 121.18, 120.76, 115.64, 71.26, 68.05, 64.20, 21.60, 21.26, 15.76; HRMS (ESI) m/z calcd for C ₂₉ H ₂₆ ClNO ₅ SH [M + H] ⁺ : 536.1294; Found: 536.1293.

example 27

0.2 mmol of N- [ 4-bromo-2- (phenylethynyl) phenyl ] -4-methylbenzenesulfonamide, 0.4 mmol of triacetylrhamnosene, 0.02 mmol of palladium acetate, 0.4 mmol of cesium carbonate, 0.4 mmol of potassium iodide and 2 ml of N, N-dimethylformamide are added into a reaction tube, and the reaction is stirred at room temperature for 6 hours to stop the reaction, then 5 ml of water is added, the reaction solution is extracted with ethyl acetate for three times, the organic phases are combined, dried by using anhydrous sodium sulfate, filtered, and the solvent is evaporated under reduced pressure to obtain a crude product, which is then separated and purified by column chromatography (in this example, the eluent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain the target product with a yield of 69%. The structural formula of the obtained product is as follows:

the structural characterization data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.21 (d, J = 8.9 Hz, 1H), 8.17 (d, J = 2.0 Hz, 1H), 7.55 – 7.40 (m, 5H), 7.40 – 7.24 (m, 3H), 7.09 (d, J = 8.1 Hz, 2H), 6.02 – 5.95 (m, 1H), 5.83 (dd, J = 10.3, 1.4 Hz, 1H), 4.92 – 4.85 (m, 2H), 4.22 (q, J = 6.8 Hz, 1H), 2.33 (s, 3H), 2.26 (s, 3H), 1.19 (d, J = 6.9 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 171.05, 145.14, 139.67, 135.85, 135.10, 133.84, 130.33, 129.64, 129.55, 129.45, 127.86, 127.61, 126.90, 124.09, 121.15, 119.58, 117.41, 116.97, 71.51, 67.51, 63.94, 21.63, 21.45, 15.31; HRMS (ESI) m/z calcd for C ₂₉ H ₂₆ BrNO ₅ SH [M + H] ⁺ : 580.0790; Found: 580.0788.

examples 28 to 49

The preparation methods of examples 28 to 49 are basically the same as the preparation method of example 1, and the structures of the obtained products are also the same, except that the reaction conditions selected for examples 28 to 49 are different, as shown in the following table 1:

TABLE 1 reaction conditions and reaction results for examples 28 to 49

The results of examples 28 to 49 show that the palladium catalyst, base, additive, solvent and temperature all have a large influence on the reaction results.

Compared with the prior art, the invention uses commercially available glycenes as raw materials, and the glycenes and the o-alkynyl aniline are subjected to series nucleophilic cyclization reaction to obtain the 2,3 site unsaturated indole carbon glycoside compound, so that the substrate universality is good, the reaction condition is mild, and the synthesis process is simple and efficient. The reaction mechanism of the invention is shown in figure 2, in the invention, o-alkynyl aniline and active bivalent palladium iodide are firstly coordinated to generate an intermediate A, the intermediate A generates an intermediate B through intramolecular nucleophilic cyclization reaction, then the intermediate B and double bonds in the glucene generate stereoselective specific addition reaction to generate an intermediate C, and finally the intermediate C is eliminated through ortho-position heteroatom to obtain the 2,3 site unsaturated indole carbon glycoside product.

The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such modifications are intended to be included in the scope of the present invention.

Claims (8)

1. A preparation method of indole carbon glycoside compounds is characterized by comprising the following steps:

adding o-alkynyl aniline shown in a formula I, glycene shown in a formula II, a palladium catalyst, alkali and an additive into a clean reactor, then adding an organic solvent, stirring and reacting for 5-10 hours at room temperature, and carrying out post-treatment after the reaction is finished to obtain the indole carbon glycoside compound III, wherein the reaction formula is shown as follows:

wherein R is ¹ Selected from H, methyl, fluorine, chlorine or bromine; r ² Selected from phenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 3-methylphenyl or 3-fluorophenyl; r ³ Selected from p-toluenesulfonyl, benzenesulfonyl or p-nitrobenzenesulfonyl; the glycene shown in the formula II is selected from one of glucene, galactene and rhamnoene; p represents a protecting group for a hydroxyl group on a saccharide, selected from acetyl or benzoyl.

2. The method for producing an indolinecoside according to claim 1, comprising: the addition amount of the glucal shown in the formula II is that the molar ratio of the compound I is (1~3): 1.

3. The method for preparing an indole carbon glycoside compound according to claim 1, wherein: the glucose alkene is triacetyl glucose alkene or tribenzoyl glucose alkene, the galactose alkene is triacetyl galactose alkene, and the rhamnosene is triacetyl rhamnosene.

4. The method for preparing an indole carbon glycoside compound according to claim 1, wherein: the palladium catalyst is one of palladium acetate and palladium iodide, and the addition amount of the palladium catalyst is 5-15% of the molar amount of the compound I.

5. The method for preparing an indole carbon glycoside compound according to claim 1, wherein: the alkali is any one of cesium carbonate, potassium carbonate, sodium carbonate, potassium phosphate, potassium hydroxide and triethylamine, and the molar ratio of the addition amount of the alkali to the compound I is (1~3): 1.

6. The method for preparing an indole carbon glycoside compound according to claim 1, wherein: the additive is any one of potassium iodide, sodium iodide and tetrabutylammonium iodide, and the molar ratio of the addition amount of the additive to the compound I is (1~3): 1.

7. The method for preparing an indole carbon glycoside compound according to claim 1, wherein: the organic solvent is N, N-dimethylformamide or N, N-dimethylacetamide, and the ratio of the addition amount of the organic solvent to the compound I is (0.5 to 2) mL: 1 mmol.

8. The method for preparing an indole carbon glycoside compound according to claim 1, wherein: the post-treatment is to extract the reaction liquid for three times by using ethyl acetate and water, combine organic phases, dry the organic phases by using anhydrous sodium sulfate, filter the organic phases, evaporate the solvent under reduced pressure to obtain a crude product, and separate and purify the crude product by column chromatography to obtain the indole carbon glycoside compound; wherein, the column chromatography separation and purification uses a mixed solvent of petroleum ether and ethyl acetate as an eluent, and the volume ratio of the petroleum ether to the ethyl acetate is (2 to 10): 1.

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