Unprotected aryl c-glycoside synthesis method and application

Abstract

The application discloses a synthesis method and application of unprotected aryl C-glycoside, and relates to the technical fields of chemistry and medicine. The synthesis method comprises the following steps: under the protection of inert gas, reacting an unprotected glycosyl donor, an acceptor, a photocatalyst, a transition metal catalyst, a ligand, a base, a free radical precursor and a solvent to obtain aryl C-glycoside. The problem to be solved by the application is that the synthesis of the existing unprotected aryl C-glycoside needs multi-step protection group operation, harsh reaction conditions and high cost. The application directly utilizes a full-hydroxyl sugar donor to perform glycosylation reaction, can simplify a synthesis route, provides a more direct way for later functional group and biological activity screening, and the method of the application can also be used for synthesizing SGLT2 inhibitor drugs. Compared with a traditional synthesis route which needs ultralow-temperature conditions (-78 DEG C) and multi-step protection group introduction and removal strategies, the application can be performed at room temperature, avoids the use of expensive reagents and multi-step complicated purification steps.

Description

Technical Field

[0001] This invention relates to the fields of chemistry and pharmaceutical technology, specifically to a method for synthesizing and applying an unprotected aryl C-glycoside. Background Technology

[0002] Glycosides are carbohydrate compounds formed by the attachment of a sugar anolyte to different atoms, such as oxyglycosides, nitrogen glycosides, and C-glycosides. Although C-glycosides are relatively rare in nature, the carbon-carbon bonds at their ends are more resistant to enzymatic and chemical hydrolysis, giving them excellent enzymatic stability and pharmaceutical properties. Among these, aromatic C-glycosides are an important class of C-glycoside compounds, with their structure consisting of a direct bond between the anolyte carbon of the sugar and the carbon atom of the aromatic ring. These compounds exhibit a wide range of biological functions, including anticancer, antiviral, and antidiabetic activities, and are therefore widely used in pharmaceutical science and biological research.

[0003] The synthesis of traditional C-glycosides relies on protecting groups to control the stereoselectivity of the reaction. However, the introduction and removal of protecting groups are not only time-consuming but also inefficient. Therefore, with the continuous development of sustainable chemistry, the direct use of unprotected glycoside donors for glycosylation has become a research hotspot. The synthesis of unprotected aryl C-glycosides is a breakthrough in the field of glycochemistry in recent years. These compounds have excellent metabolic stability because all hydroxyl groups on the sugar ring are exposed and unprotected, and are directly linked to the aryl group by carbon-carbon bonds (C-glycosidic bonds). They are the core structure of many drugs, such as "levofloxacin" drugs for treating diabetes. Therefore, the direct use of fully hydroxyl sugar donors for glycosylation not only simplifies the synthetic route but also provides a more direct way for subsequent functionalization and bioactivity screening. However, the synthesis of unprotected aryl C-glycosides in the present technology has technical problems such as multiple protecting group operations, harsh reaction conditions, and high synthesis costs. Summary of the Invention

[0004] The purpose of this invention is to at least solve one of the technical problems existing in the prior art, and to provide a method for synthesizing unprotected aryl C-glycosides and their applications, specifically a method for the direct synthesis of unprotected aryl C-glycosides via photoredox nickel-catalyzed cross-coupling.

[0005] The technical solution of the present invention is as follows: In a first aspect, the present invention provides a method for synthesizing an unprotected aryl C-glycoside, the method comprising: reacting an unprotected glycosyl donor, an acceptor, a photocatalyst, a transition metal catalyst, a ligand, a base, a free radical precursor and a solvent under an inert gas atmosphere to obtain an aryl C-glycoside. The unprotected glycosyl donor is at least one of the following: unprotected o-alkynylphenylthioglucoside, unprotected o-alkynylphenylthiomannoside, unprotected o-alkynylphenylthiogalactoside, unprotected o-alkynylphenylthio(2-acetamino)glucoside, unprotected o-alkynylphenylthio(2-acetamino)galactoside, unprotected o-alkynylphenylthiorhamnoside, unprotected o-alkynylphenylthiofucoside, unprotected o-alkynylphenylthioxyloside, unprotected o-alkynylphenylthioriboside, and unprotected o-alkynylphenylthiomaltobiside. The acceptor is at least one selected from 4-methoxyiodobenzene, 3-methoxyiodobenzene, 2-methoxyiodobenzene, 4-tert-butyliodobenzene, 4-trifluoromethyliodobenzene, ethyl p-iodobenzoate, 4-iodobiphenyl, 4-chloroiodobenzene, 4-bromoiodobenzene, 2-iodopyrazine, o-diiodobenzene, p-diiodobenzene, 3-iodobenzothiophene, and tert-butyl 5-iodo-1H-indole-1-carboxylic acid.

[0006] Optionally, the photocatalyst is ruthenium tripyridine chloride hexahydrate (Ru(bpy)3Cl2·6H2O), tris(1,10-phenanthroline)ruthenium(II) bis(hexafluorophosphate) (Ru(1,10Phen)2PF6), tris(2,2'-bipyridine)ruthenium di(tetrafluoroborate) (Ru(bpy)3BF4), bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium di(hexafluorophosphate) (Ir[dFCF3(ppy)2(dtbbpy)]PF6), or planar-tris(2-phenylpyridine)iridium ( fac At least one of -Ir(ppy)3) and 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN); The transition metal catalyst is at least one of ethylene glycol dimethyl ether nickel bromide (NiBr2·DME), nickel(II) bromide 2-methoxyethyl ether complex (NiBr2·diglyme), nickel(II) trifluoromethanesulfonate (Ni(OTf)2), and bis(triphenylphosphine) nickel chloride (Ni(PPh3)3Cl2).

[0007] Optionally, the ligand is at least one of L1 to L6: ; The base is at least one of triethylenediamine, tetramethylguanidine, and triethylamine.

[0008] Optionally, the free radical precursor is sodium cyclopropane sulfinate; the solvent is DMF.

[0009] Optionally, the molar ratio of the unprotected glycosyl donor, acceptor, photocatalyst, transition metal catalyst, ligand, base, and free radical precursor is 1:1~2:0.01:0.05~0.15:0.1~0.14:1.5~2.5:2.5~3.5.

[0010] Optionally, the reaction conditions include: 10 W 455 nm blue light irradiation at room temperature for 12 to 48 hours.

[0011] Secondly, the present invention provides the application of the described synthesis method in the synthesis of SGLT2 inhibitor drugs.

[0012] Optionally, the SGLT2 inhibitor includes at least one of canagliflozin, dapagliflozin, and empagliflozin.

[0013] Thirdly, the present invention provides a method for the continuous synthesis of empagliflozin, the method comprising the following steps: Unprotected o-alkynylphenyl thioglycoside, (3S)-3-[4-[(2-chloro-5-iodophenyl)methyl]phenoxy]tetrahydrofuran, ruthenium tripyridine chloride hexahydrate (Ru(bpy)3Cl2·6H2O), nickel(II) 2-methoxyethyl ether complex (NiBr2·diglyme), 4,4',4''-tritert-butyl-2,2',6',2''-terpyridine, triethylenediamine, and sodium cyclopropane sulfinate were added to the reaction vessel, nitrogen gas was purged, and then ultra-dry DMSO was added as a solvent to obtain the reaction solution. The reaction solution was pumped into the flow photoreactor at a flow rate of 0.8 mL / min, and the reaction solution was kept in the microchannel reaction plate for 2 hours at 25 °C and under the illumination of a 455 nm LED lamp. After the reaction was completed, the product was diluted with ethyl acetate, washed with saturated sodium chloride solution, concentrated, and purified by column chromatography to obtain empagliflozin.

[0014] This invention has at least one of the following beneficial effects: 1. This invention provides a method for the direct synthesis of unprotected 1,2-trans-aryl C-glycosides. Using unprotected sugar substrates and aryl iodides as reactants, unprotected aryl C-glycosides are directly synthesized via photoredox nickel-catalyzed cross-coupling, achieving a yield of up to 90%. This invention directly utilizes all-hydroxy sugar donors for glycosylation, which not only simplifies the synthetic route but also provides a more direct approach for subsequent functionalization and bioactivity screening.

[0015] 2. The method of the present invention can also synthesize SGLT2 inhibitor drugs. Compared with the traditional synthetic route, which requires ultra-low temperature conditions (-78 ℃) and a multi-step protecting group introduction-removal strategy, the method of the present invention can be carried out at room temperature and avoids the use of expensive reagents and multiple cumbersome column chromatography purification steps. Attached Figure Description

[0016] Figure 1 A schematic diagram for screening and optimizing reaction conditions and reaction routes; Figure 2 A schematic diagram of reaction routes for screening and optimizing aryl substrates; Figure 3 A schematic diagram of the reaction route for screening and optimizing unprotected carbohydrate substrates; Figure 4 A schematic diagram illustrating the reaction pathway for applying the method of this invention to SGLT2 inhibitor drugs; Figure 5 A schematic diagram of the continuous flow reaction route for the gram-level synthesis of empagliflozin; Figure 6 This is a schematic diagram of the reaction mechanism predicted by the present invention; Figure 7 A schematic diagram of the continuous flow reaction route for the gram-level synthesis of canagliflozin; Figure 8 A schematic diagram of the continuous flow reaction route for the gram-scale synthesis of dapagliflozin. Detailed Implementation

[0017] To make the technical problems solved, the technical solutions, and the beneficial effects of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0018] This invention uses unprotected o-alkynylphenyl thioglycoside (3-1a) as the donor and iodobenzene (3-2a) as the acceptor. The initial reaction system consists of tris(1,10-phenanthroline)ruthenium(II)bis(hexafluorophosphate) (Ru(1,10Phen)2PF6) as the photocatalyst, nickel dimethyl ether bromide (NiBr2·DME) as the transition metal catalyst, 4,4',4''-tritert-butyl-2,2',6',2''-terpyridine (L6) as the ligand, triethylenediamine (DABCO) as the base, and sodium cyclopropane sulfinate as the radical precursor. The reaction time is 36 h, and aryl C-glycoside (3-3a) is synthesized in 63% yield.

[0019] (1) Screening of reaction conditions like Figure 1As shown, this invention first uses unprotected o-alkynylphenyl thioglycoside (3-1a) and iodobenzene (3-2a) as model substrates. The photocatalysts (see items 2-6 in Table 1) were first screened. When 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN) was used as the photocatalyst, the yield was only 27%. When Ir was used as the catalyst, the yield increased slightly to 35%. When Ru was used as the photocatalyst, the yield significantly improved, especially when using ruthenium tripyridine chloride hexahydrate (Ru(bpy)3Cl2·6H2O) as the photocatalyst, the yield reached 72%.

[0020] Subsequently, transition metal catalysts (see items 7-10 in Table 1) were screened, and the yield increased from 72% to 87% when using the nickel(II) 2-methoxyethyl ether complex (NiBr2·diglyme).

[0021] Then, the ligands (see items 11-15 in Table 1) were screened, and it was found that using the current ligand had the best effect.

[0022] Next, the bases (see items 16-20 in Table 1) were screened. When strong organic bases such as 1,8-diazacyclo[5,4,0]undecene-7 (DBU) and 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG) (see items 16 and 17 in Table 1) were used, no product was detected and most of the raw materials remained.

[0023] Finally, the reaction time (see items 21-22 in Table 1) was screened, and it was found that when the reaction time was 12 hours, some raw materials were still remaining, while when the reaction time was 36 hours, the raw materials were completely reacted.

[0024] Table 1. Condition Filtering and Optimization "Yield" refers to the yield of the separated product.

[0025] Note: NR indicates no product detected, and Trace indicates trace amount.

[0026] After systematic screening and optimization of reaction conditions, the optimal reaction conditions were finally determined as follows: under nitrogen protection, using unprotected thioglycoside 3-1a (0.1 mmol, 1.0 equiv.) as the donor, p-methoxyiodobenzene 3-2a (0.15 mmol, 1.5 equiv.) as the acceptor, Ru(bpy)3Cl2·6H2O (1 mol%) as the photocatalyst, NiBr2·diglyme (10 mol%) as the transition metal catalyst, 4,4',4''-tritert-butyl-2,2',6',2''-terpyridine (12 mol%) as the ligand, triethylenediamine (2.0 equiv.) as the base, sodium cyclopropanesulfinate (3.0 equiv.) as the radical precursor, and DMF (1.0 mL) as the solvent, at room temperature for 10 minutes. After 36 hours of blue light irradiation, the final product 3-3a was obtained in 90% yield (see item 1 in Table 1), and the product was confirmed to be a single product by NMR analysis. β Configuration.

[0027] (2) Expansion of reaction substrates After determining the optimal conditions, such as Figure 2 As shown, this invention explored the range of reaction substrates and found that various aryl halides could participate smoothly in the reaction, compatible with both electron-donating substrates (3-3d, 3-3g) and electron-deficient aryl ring acceptors (3-3e, 3-3f). Furthermore, electron-deficient compounds showed better reaction performance than electron-donating compounds. However, ortho-substituted aryl iodides (3-3b) exhibited poor reaction performance, with a yield of only 27%. The meta-substrate (3-3c) had a yield of 85%, indicating that steric hindrance of the acceptor affected the reaction efficiency. In addition to various aryl iodides containing different functional groups, heteroaryl substrates could also participate smoothly in the reaction.

[0028] like Figure 3 As shown, the next step is to expand the substrate to include sugars. Not only do pyranose monosaccharides react smoothly (3-3o, 3-3p), but furanose ribose also participates in the reaction. Next, the substrate to disaccharides was expanded, achieving a yield of 76% for the substrate (3-3w).

[0029] (3) Synthetic application After the work of substrate expansion is completed, such as Figure 4 As shown, this invention extends the practicality of this method by attempting to synthesize SGLT2 inhibitor drugs. Compared to traditional synthetic routes that require ultra-low temperature conditions (-78 °C) and multi-step protecting group introduction-removal strategies, the method of this invention can be carried out at room temperature and avoids the use of expensive reagents and multiple cumbersome column chromatography purification steps.

[0030] Subsequently, as Figure 5 As shown, this invention selects empagliflozin, which has a high synthesis yield, as a model substrate and extends its synthesis to a continuous flow reaction system.

[0031] Unprotected o-alkynylphenyl thioglycoside 3-1a (1.6 g, 4.0 mmol), (3S)-3-[4-[(2-chloro-5-iodophenyl)methyl]phenoxy]tetrahydrofuran S1 (2.5 g, 6.0 mmol), and Ru(bpy)3Cl2·6H2O (25 mg, 1 mol%) were used as photocatalysts. NiBr2·diglyme (141 mg, 10 mol%), 4,4',4''-tritert-butyl-2,2',6',2''-terpyridine (193 mg, 12 mol%), triethylenediamine (898 mg, 2.0 equiv.), and sodium cyclopropanesulfonate (1.56 g, 3.0 equiv.) were added to a 100 mL reaction flask, which was purged with nitrogen. Then, ultra-dry DMSO (70 mL, 0.06 mmol) was added. M) was used as the solvent. The reaction solution was then pumped into an 8 mL flow photoreactor at a flow rate of 0.8 mL / min using a peristaltic pump. The reaction solution was kept in a microchannel reaction plate at 25 °C under irradiation by 455 nm LEDs (8 x 10 W LEDs) for 2 hours. After the reaction, the solution was diluted with ethyl acetate, washed four times with saturated sodium chloride solution, and concentrated. The crude product was purified by column chromatography to obtain Empagliflozin (863 mg, 48%, single). β Configuration).

[0032] (4) Mechanism speculation like Figure 6 As shown, photoexcited Ru(III) oxidizes sodium cyclopropane sulfinate to generate a sulfonyl radical, which adds to the carbon-carbon triple bond of the o-alkynylphenyl thioglycoside donor to generate an alkenyl radical intermediate. The alkenyl radical then ring-closes to the sulfur atom to generate a leaving group B2, forming a glycosyl radical intermediate. Simultaneously, Ni(O) undergoes oxidative addition with an aryl halide to form an aryl nickel(II) intermediate. The glycosyl radical combines with the aryl nickel intermediate to generate a Ni(III) intermediate, which subsequently undergoes reductive elimination to form the target aryl group. C - Glycoside and release Ni(I). Finally, Ru(I) reduces Ni(I) to regenerate Ni(0) and Ru(II), completing the catalytic cycle. The leaving group generated in the reaction was purified by column chromatography, and its structure was confirmed by NMR.

[0033] Based on the above research, this invention provides a method for the direct synthesis of unprotected 1,2-trans-aryl glycosides. This method reacts a stable, unprotected o-alkynylphenyl thioglycoside with an aryl iodide to generate an aryl glycoside. This method reacts smoothly with various aryl iodides and yields the corresponding products in a single β-configuration; however, the reaction of o-methoxyiodobenzene is less efficient due to the steric hindrance of the aryl iodides. Furthermore, this reaction can also react with heteroaryl bromides to generate the corresponding products. Next, this invention also utilizes a continuous flow chromatography method to synthesize the drug molecule Empagliflozin, which effectively shortens the reaction time. The leaving group B2 obtained by column chromatography further confirms that the glycosyl radical is generated from the key addition-cyclization reaction of the alkynyl group.

[0034] The present invention will be further described in detail below with reference to specific embodiments, but the present invention is not limited to the following specific embodiments.

[0035] Example 1 In a 10 mL Schlenk tube equipped with a magnetic flux, 0.1 mmol (1.0 equiv.) of perhydroxyl o-alkynylphenyl thioglycoside donor 3-1a, aryl iodine 3-2a (4-methoxyiodobenzene, 0.15 mmol, 1.5 equiv.), Ru(bpy)3Cl2·6H2O (1 mol%), NiBr2·diglyme (10 mol%), 4,4',4''-tritert-butyl-2,2',6',2''-terpyridine (12 mol%), triethylenediamine (2.0 equiv.), and sodium cyclopropane sulfinate (3.0 equiv.) were added. The tube was then purged with nitrogen, and 1.0 mL of DMF solvent was added under nitrogen atmosphere. The reaction was carried out at room temperature for 36 hours under 10 W 455 nm blue light irradiation. The reaction was monitored by TLC. After the reaction was complete, the solvent was removed by vortexing, and the product compound (3-3a) was obtained by column chromatography.

[0036] Compound (3-3a): After separation by silica gel chromatography, a colorless oily substance (24.5 mg, eluent: DCM / MeOH = 25 / 1) was obtained in 90% yield.

[0037] 1 H NMR (400 MHz, DMSO- d 6) δ 7.25 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 8.4Hz, 2H), 4.93 (d, J= 5.0 Hz, 2H), 4.72 (d, J = 5.7 Hz, 1H), 4.45 (t, J = 5.8Hz, 1H), 3.96 (d, J = 9.4 Hz, 1H), 3.73 (s, 3H), 3.71 – 3.64 (m, 1H), 3.51 –3.43 (m, 1H), 3.30 – 3.10 (m, 4H). The leaving group B2 was obtained by column chromatography. Leaving group B2: ; 1 H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 8.3 Hz, 1H), 7.74 (d, J = 7.9 Hz,1H), 7.47 – 7.39 (m, 3H), 7.38 – 7.31 (m, 1H), 6.87 (dd, J = 8.8, 1.7 Hz, 2H), 3.77 (d, J = 1.5 Hz, 3H), 2.52 – 2.29 (m, 1H), 1.21 – 0.97 (m, 2H), 0.85 –0.56 (m, 2H). This indicates that the glycosyl radical is generated from the key addition-cyclization reaction of the perhydroxyl o-alkynylphenyl thioglycoside.

[0038] Example 2 The difference from Example 1 is that “4-methoxyiodobenzene” is replaced with “2-methoxyiodobenzene”, while the rest is the same as in Example 1, and the corresponding product compound (3-3b) is obtained.

[0039] Compound (3-3b): After separation by silica gel chromatography, a colorless oil (7.3 mg, eluent: DCM / MeOH = 25 / 1) was obtained in a yield of 27%.

[0040] 1 H NMR (400 MHz, CDCl3) δ8.98 (d, J = 7.6 Hz, 1H), 8.83 (t, J = 8.0 Hz, 1H), 8.53 (d, J = 8.1 Hz, 2H), 6.27 (d,J = 9.2 Hz, 1H), 5.41 (d, J = 12.0 Hz, 1H), 5.38 (d, J = 1.7 Hz, 3H), 5.29 – 5.19 (m, 1H), 5.08 (m, 2H), 4.96 (d, J =6.4 Hz, 2H). 13 C NMR (100 MHz, CDCl3) δ 159.3, 130.2, 129.4, 128.9, 121.6, 112.0,82.4, 80.0, 76.4, 76.0, 72.2, 63.2, 56.2. Example 3 The difference from Example 1 is that "4-methoxyiodobenzene" is replaced with "3-methoxyiodobenzene", resulting in the corresponding product compound (3-3c).

[0041] Compound (3-3c): After separation by silica gel chromatography, a colorless oil was obtained in 85% yield (22.9 mg, eluent: DCM / MeOH = 25 / 1).

[0042] 1 H NMR (400 MHz, Methanol- d 4) δ 7.23 (t, J = 8.0 Hz, 1H), 6.99 (dd, J =4.2, 2.3 Hz, 2H), 6.84 (dd, J = 8.2, 2.3 Hz, 1H), 4.10 (d, J = 9.3 Hz, 1H), 3.95 – 3.83 (m, 1H), 3.78 (s, 3H), 3.70 (dd, J = 11.9, 5.1 Hz, 1H), 3.51 –3.44 (m, 1H), 3.39 (dd, J = 14.0, 8.5 Hz, 2H), 3.34 (s, 1H). 13 C NMR (100 MHz, Methanol- d4) δ 159.6, 140.9, 128.6, 120.0, 113.1,113.0, 82.2, 80.8, 78.4, 75.0, 70.5, 61.7, 54.3. Example 4 The difference from Example 1 is that "4-methoxyiodobenzene" was replaced with "4-tert-butyliodobenzene", and the corresponding product compound (3-3d) was obtained.

[0043] Compound (3-3d): After separation by silica gel chromatography, a colorless oil was obtained in 78% yield (23.1 mg, eluent: DCM / MeOH = 25 / 1).

[0044] 1 H NMR (400 MHz, Methanol- d 4) δ 7.55 – 7.11 (m, 4H), 4.10 (d, J = 9.3Hz, 1H), 3.87 (d, J = 11.6 Hz, 1H), 3.75 – 3.64 (m, 1H), 3.50 – 3.44 (m, 1H), 3.42 – 3.36 (m, 3H), 1.30 (d, J = 1.9 Hz, 9H). 13 C NMR (100 MHz, Methanol- d 4) δ 150.6, 136.4, 127.4, 124.6, 82.1,80.8, 78.4, 74.9, 70.6, 61.8, 34.0, 30.4. Example 5 The difference from Example 1 is that “4-methoxyiodobenzene” is replaced with “4-trifluoromethyliodobenzene”, resulting in the corresponding product compound (3-3e).

[0045] Compound (3-3e): After separation by silica gel chromatography, a colorless oily substance (30.4 mg, eluent: DCM / MeOH = 25 / 1) was obtained in 98% yield.

[0046] 1 H NMR (400 MHz, Methanol- d 4)δ 7.62 (d, J= 1.7 Hz, 4H), 4.23 (d, J =9.4 Hz, 1H), 3.90 (d, J = 11.9 Hz, 1H), 3.79 – 3.66 (m, 1H), 3.55 – 3.39 (m, 3H), 3.28 (s, 1H). 13 C NMR (100 MHz, Methanol- d 4) δ144.1, 128.0, 124.4 (q), 81.3, 80.8,78.3, 75.2, 70.4, 61.6. Example 6 The difference from Example 1 is that "4-methoxyiodobenzene" was replaced with "ethyl p-iodobenzoate", resulting in the corresponding product compound (3-3f).

[0047] Compound (3-3f): After separation by silica gel chromatography, a colorless oil (24.7 mg, eluent: DCM / MeOH = 25 / 1) was obtained in 83% yield.

[0048] 1 H NMR (400 MHz, Methanol- d 4)δ8.13 – 7.90 (m, 2H), 7.65 – 7.37 (m,2H), 4.42 – 4.31 (m, 2H), 4.22 (d, J = 9.5 Hz, 1H), 3.90 (d, J = 11.9 Hz, 1H), 3.73 (dd, J = 12.1, 4.4 Hz, 1H), 3.55 – 3.39 (m, 3H), 3.34 (s, 1H), 1.39 (t, J = 7.1, 1.4 Hz, 3H). 13 C NMR (100 MHz, Methanol- d 4) δ166.6, 145.0, 129.6, 128.7, 127.5,81.6, 80.8, 78.4, 75.1, 70.4, 61.7, 60.7, 13.2. Example 7 The difference from Example 1 is that "4-methoxyiodobenzene" was replaced with "4-iodobiphenyl", and the corresponding product compound (3-3g) was obtained.

[0049] Compound (3-3g): After separation by silica gel chromatography, a colorless oil (25.3 mg, eluent: DCM / MeOH = 25 / 1) was obtained in 79% yield.

[0050] 1 H NMR (400 MHz, Methanol- d 4)δ 7.59 (d, J = 7.8 Hz, 4H), 7.50 (d, J =7.9 Hz, 2H), 7.41 (t, J = 7.5 Hz, 2H), 7.31 (t, J = 7.4 Hz, 1H), 4.19 (d, J =9.3 Hz, 1H), 3.90 (d, J = 12.1 Hz, 1H), 3.72 (dd, J = 12.4, 4.4 Hz, 1H), 3.55 –3.47 (m, 1H), 3.42 (d, J = 9.8 Hz, 3H). 13 C NMR (100 MHz, Methanol- d 4)δ 144.8, 144.6, 142.5, 132.4, 132.0,130.9, 130.5, 130.2, 85.9, 84.8, 82.4, 79.0, 74.5, 65.7. Example 8 The difference from Example 1 is that "4-methoxyiodobenzene" was replaced with "4-chloroiodobenzene", and the corresponding product compound (3-3h) was obtained.

[0051] Compound (3-3h): After separation by silica gel chromatography, a colorless oil (21.5 mg, eluent: DCM / MeOH = 25 / 1) was obtained in 78% yield.

[0052] 1 H NMR (400 MHz, Methanol- d4)δ 7.46 – 7.37 (m, 2H), 7.32 (dd, J = 8.5, 2.0 Hz, 2H), 4.13 (d, J = 9.5 Hz, 1H), 3.88 (d, J = 11.6 Hz, 1H), 3.70 (dd, J =12.0, 4.7 Hz, 1H), 3.52 – 3.37 (m, 3H), 3.31 (s, 1H). 13 C NMR (100 MHz, Methanol- d 4)δ138.4, 133.1, 129.1, 127.7, 81.3, 80.8,78.3, 75.1, 70.4, 61.7. Example 9 The difference from Example 1 is that “4-methoxyiodobenzene” is replaced with “4-bromoiodobenzene” to obtain the corresponding product compound (3-3i).

[0053] Compound (3-3i): After separation by silica gel chromatography, a colorless oily substance (23.9 mg, eluent: DCM / MeOH = 25 / 1) was obtained in 75% yield.

[0054] 1 H NMR (400 MHz, Methanol- d 4) δ 7.48 (d, J = 8.4 Hz, 2H), 7.35 (d, J =8.4 Hz, 2H), 4.12 (d, J = 9.5 Hz, 1H), 3.88 (dd, J = 11.9, 1.8 Hz, 1H), 3.70(dd, J = 11.9, 4.9 Hz, 1H), 3.52 – 3.39 (m, 3H), 3.34 (s, 1H). 13 C NMR (100 MHz, Methanol- d 4)δ140.2, 132.0, 130.8, 122.5, 82.7, 82.1,79.7, 76.4, 71.8, 63.0. Example 10 The difference from Example 1 is that “4-methoxyiodobenzene” was replaced with “4-iodobenzyl alcohol” to obtain the corresponding product compound (3-3j).

[0055] Compound (3-3j): After separation by silica gel chromatography, a colorless oil was obtained in 64% yield (17.3 mg, eluent: DCM / MeOH = 15 / 1).

[0056] 1 H NMR (400 MHz, Methanol- d 4)δ 7.43 – 7.37 (m, 2H), 7.35 – 7.29 (m,2H), 4.59 (s, 2H), 4.13 (dd, J = 9.5, 1.8 Hz, 1H), 3.87 (d, J = 11.8 Hz, 1H), 3.70 (dd, J = 12.1, 4.8 Hz, 1H), 3.53 – 3.36 (m, 4H). 13 C NMR (100 MHz, Methanol- d 4)δ141.0, 138.4, 127.6, 126.3, 82.0, 80.8,78.4, 75.1, 70.6, 63.6, 61.8. Example 11 The difference from Example 1 is that “4-methoxyiodobenzene” was replaced with “2-iodo-6-methoxypyridine” to obtain the corresponding product compound (3-3k).

[0057] Compound (3-3k): After separation by silica gel chromatography, a colorless oil (25.6 mg, eluent: DCM / MeOH = 15 / 1) was obtained in 94% yield.

[0058] 1 H NMR (400 MHz, Methanol- d 4) δ 8.13 (s, 1H), 7.76 (dd, J = 8.7, 2.3 Hz, 1H), 6.79 (d, J = 8.8 Hz, 1H), 4.14 (d, J= 9.5 Hz, 1H), 3.99 – 3.79 (m, 4H), 3.75 – 3.66 (m, 1H), 3.50 – 3.38 (m, 3H), 3.34 (s, 1H). 13 C NMR (100 MHz, Methanol- d 4)δ164.1, 145.9, 138.4, 128.4, 109.7,80.9, 79.5, 78.3, 74.7, 70.4, 61.7, 52.7. Example 12 The difference from Example 1 is that “4-methoxyiodobenzene” was replaced with “7-iodoquinoline” to obtain the corresponding product compound (3-3l).

[0059] Compound (3-3l): After separation by silica gel chromatography, a white solid (15.3 mg, eluent: DCM / MeOH = 15 / 1) was obtained in 52% yield.

[0060] 1 H NMR (400 MHz, DMSO- d 6)δ8.90 (d, J = 4.1 Hz, 1H), 8.41 (d, J = 8.3 Hz,1H), 8.10 – 7.91 (m, 2H), 7.79 (d, J = 8.7 Hz, 1H), 7.55 (dd, J = 8.3, 4.2 Hz, 1H), 4.25 (d, J = 9.4 Hz, 1H), 3.75 (d, J = 11.8 Hz, 1H), 3.51 (dd, J = 11.9, 5.8 Hz, 1H), 3.35 (q, J = 8.1, 7.7 Hz, 2H), 3.26 (d, J = 9.3 Hz, 2H). 13 C NMR (100 MHz, DMSO- d6)δ 150.49, 147.41, 139.29, 136.91, 130.20,128.26, 127.87, 127.09, 121.89, 81.76, 81.56, 78.79, 75.36, 70.83, 61.88. Example 13 The difference from Example 1 is that “4-methoxyiodobenzene” was replaced with “3-iodo-9H-carbazole” to obtain the corresponding product compound (3-3m).

[0061] Compound (3-3m): After separation by silica gel chromatography, a white solid (31.6 mg, eluent: DCM / MeOH = 15 / 1) was obtained in 96% yield.

[0062] 1 H NMR (400 MHz, Methanol- d 4) δ 8.13 (s, 1H), 8.05 (d, J = 7.9 Hz, 1H),7.49 – 7.40 (m, 3H), 7.35 (t, J = 7.7 Hz, 1H), 7.14 (t, J = 7.5 Hz, 1H), 4.31(d, J = 7.7 Hz, 1H), 3.91 (d, J = 11.9 Hz, 1H), 3.75 (dd, J = 12.3, 4.9 Hz, 1H),3.65 – 3.43 (m, 4H). 13 C NMR (100 MHz, Methanol- d 4)δ140.5, 140.0, 129.5, 125.4, 125.2,122.9, 122.8, 119.6, 119.3, 118.3, 110.3, 109.9, 83.0, 80.9, 78.5, 75.2,70.7, 61.9. Example 14 The difference from Example 1 is that “4-methoxyiodobenzene” was replaced with “5-iodo-1H-indole-1-carboxylic acid tert-butyl ester”, resulting in the corresponding product compound (3-3n).

[0063] Compound (3-3n): After separation by silica gel chromatography, a white solid (27.3 mg, eluent: DCM / MeOH = 20 / 1) was obtained in 72% yield.

[0064] 1 H NMR (400 MHz, Methanol- d 4)δ8.08 (d, J = 8.4 Hz, 1H), 7.63 (s, 1H), 7.59 (d, J = 3.6 Hz, 1H), 7.37 (d, J = 8.4 Hz, 1H), 6.60 (d, J = 3.5 Hz, 1H), 4.22 (d, J = 8.9 Hz, 1H), 3.89 (d, J = 11.8 Hz, 1H), 3.73 (dd, J = 12.2, 4.8 Hz,1H), 3.57 – 3.41 (m, 4H), 1.66 (d, J = 1.9 Hz, 9H). 13 C NMR (100 MHz, Methanol- d 4)δ151.0, 136.3, 135.3, 131.8, 127.1,125.3, 121.5, 115.5, 108.5, 84.9, 83.8, 82.2, 79.8, 76.6, 72.0, 63.2, 28.4. Example 15 The difference from Example 1 is that “4-methoxyiodobenzene” was replaced with “3-iodobenzothiophene” to obtain the corresponding product compound (3-3o).

[0065] Compound (3-3o): After separation by silica gel chromatography, a colorless oil was obtained in 34% yield (10.0 mg, eluent: DCM / MeOH = 15 / 1).

[0066] 1 H NMR (400 MHz, Methanol- d 4)δ8.02 (d, J = 7.6 Hz, 1H), 7.86 (d, J= 7.6Hz, 1H), 7.60 (s, 1H), 7.42 – 7.23 (m, 2H), 4.60 (d, J = 9.8 Hz, 1H), 3.91 (d, J = 12.0 Hz, 1H), 3.73 (q, J = 7.4, 5.8 Hz, 2H), 3.52 (dd, J = 19.7, 7.3 Hz, 3H). 13 C NMR (100 MHz, Methanol- d 4)δ141.9, 139.7, 135.7, 125.9, 125.3,124.9, 124.3, 123.5, 82.3, 80.0, 78.9, 75.2, 72.0, 63.1. Example 16 The difference from Example 1 is that "all-hydroxyl o-alkynylphenyl thioglycoside" was replaced with "unprotected o-alkynylphenyl thiomannoglycoside", resulting in the corresponding product compound (3-3p).

[0067] Compound (3-3p): After separation by silica gel chromatography, a colorless oil (25.0 mg, eluent: DCM / MeOH = 20 / 1) was obtained in 92% yield.

[0068] 1 H NMR (400 MHz, DMSO- d 6)δ 7.25 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.2Hz, 2H), 4.67 (d, J = 5.4 Hz, 1H), 4.53 (t, J = 5.3 Hz, 2H), 4.37 (d, J = 4.7Hz, 1H), 3.88 (d, J = 9.2 Hz, 1H), 3.75 (d, J = 4.4 Hz, 1H), 3.72 (s, 3H), 3.53– 3.46 (m, br, 3H), 3.44 (d, J = 4.4 Hz, 1H). 13C NMR (100 MHz, DMSO - d 6)δ158.5, 132.8, 129.0, 113.0, 81.7, 79.2,75.1, 71.5, 68.9, 60.9, 55.0. Example 17 The difference from Example 1 is that "all-hydroxyl o-alkynylphenyl thioglycoside" was replaced with "unprotected o-alkynylphenyl thiogalactoside", resulting in the corresponding product compound (3-3q).

[0069] Compound (3-3q): After separation by silica gel chromatography, a white solid (22.7 mg, eluent: DCM / MeOH = 20 / 1) was obtained in 84% yield.

[0070] 1 H NMR (400 MHz, Methanol- d 4) δ 7.38 (d, J = 8.3 Hz, 2H), 6.88 (d, J =8.5 Hz, 2H), 4.02 (d, J = 9.2 Hz, 1H), 3.96 (d, J = 3.2 Hz, 1H), 3.75 (d, J =18.5 Hz, 6H), 3.65 – 3.53 (m, 2H). . 13 C NMR (100 MHz, Methanol- d 4)δ 159.5, 131.7, 129.0, 113.0, 82.6,79.4, 75.1, 72.0, 69.6, 61.5, 54.3. Example 18 The difference from Example 1 is that "all-hydroxyl o-alkynylphenyl thioglycoside" was replaced with "unprotected 2-acetamino o-alkynylphenyl thioglycoside", resulting in the corresponding product compound (3-3r).

[0071] Compound (3-3r): After separation by silica gel chromatography, a colorless oil was obtained in 62% yield (14.0 mg, eluent: DCM / MeOH = 15 / 1).

[0072] 1H NMR (400 MHz, Methanol- d 4) δ7.29 (d, J = 8.8 Hz, 2H), 6.83 (d, J =8.8 Hz, 2H), 4.23 (d, J = 10.1 Hz, 1H), 3.93 – 3.82 (m, 2H), 3.76 (s, 3H), 3.70 (dd, J = 11.9, 5.6 Hz, 1H), 3.55 (dd, J = 10.0, 8.2 Hz, 1H), 3.48 – 3.39(m, 2H), 1.73 (s, 3H). 13 C NMR (100 MHz, Methanol- d 4)δ171.5, 159.6, 130.7, 128.6, 112.9,80.9, 80.6, 76.2, 71.1, 61.8, 56.7, 54.2, 21.3. Example 19 The difference from Example 1 is that "all-hydroxyl o-alkynylphenyl thioglycoside" was replaced with "unprotected o-alkynylphenyl thiofucoside", resulting in the corresponding product compound (3-3t).

[0073] Compound (3-3t): After separation by silica gel chromatography, a white solid (13.4 mg, eluent: DCM / MeOH = 30 / 1) was obtained in 52% yield.

[0074] 1 H NMR (400 MHz, Methanol- d 4) δ 7.48 – 7.32 (m, 2H), 7.00 – 6.78 (m, 2H), 4.00 (dd, J = 9.4, 2.0 Hz, 1H), 3.78 (d, J = 1.9 Hz, 3H), 3.73 (q, J = 5.0, 2.6 Hz, 2H), 3.68 (dd, J = 9.5, 1.9 Hz, 1H), 3.60 – 3.53 (m, 1H), 1.27 (dd, J=6.5, 1.9 Hz, 3H). 13 C NMR (100 MHz, Methanol- d 4) δ160.9, 133.1, 130.4, 114.4, 83.9, 76.7, 76.0, 73.8, 73.0, 55.7, 17.3. Example 20 The difference from Example 1 is that "all-hydroxyl o-alkynylphenyl thioglycoside" was replaced with "unprotected o-alkynylphenyl thiorhamnoside", resulting in the corresponding product compound (3-3u).

[0075] Compound (3-3u): After separation by silica gel chromatography, a white solid (16.3 mg, eluent: DCM / MeOH = 30 / 1) was obtained in 64% yield. α : β = 10 : 1.

[0076] α: 1 H NMR (400 MHz, Methanol- d 4) δ 7.33 (d, J = 8.3 Hz, 2H), 6.93 (dd, J = 8.7, 1.8 Hz, 2H), 4.88 (d, J = 3.6 Hz, 1H), 4.43 (q, J = 2.6 Hz, 1H), 3.79(d, J = 1.6 Hz, 3H), 3.62 – 3.50 (m, 2H), 3.41 (t, J = 6.7 Hz, 1H), 1.31 (dd, J = 6.4, 1.7 Hz, 3H). 13 C NMR (100 MHz, Methanol- d 4)δ160.5, 131.3, 128.8, 115.0, 78.3, 74.5,72.8, 72.3, 71.8, 55.7, 17.9. Example 21 The difference from Example 1 is that "all-hydroxyl o-alkynylphenyl thioglycoside" was replaced with "unprotected o-alkynylphenyl xyloside", resulting in the corresponding product compound (3-3v).

[0077] Compound (3-3v): After separation by silica gel chromatography, a colorless oil was obtained in 71% yield (17.0 mg, eluent: DCM / MeOH = 20 / 1).

[0078] 1 H NMR (400 MHz, Methanol- d 4) δ7.29 (d, J = 8.0 Hz, 2H), 6.89 (d, J =8.2 Hz, 2H), 4.00 (d, J = 8.8 Hz, 1H), 3.95 (dd, J = 11.0, 5.3 Hz, 1H), 3.78(d, J = 1.9 Hz, 3H), 3.68 – 3.56 (m, 1H), 3.45 – 3.35 (m, 2H), 3.33 (s, 1H). 13 C NMR (100 MHz, Methanol- d 4)δ 161.0, 132.8, 130.0, 114.5, 84.2,79.9, 76.2, 71.6, 71.3, 55.7. Example 22 The difference from Example 1 is that "all-hydroxyl o-alkynylphenyl thioglycoside" was replaced with "unprotected o-alkynylphenyl thioriboglycoside", resulting in the corresponding product compound (3-3w).

[0079] Compound (3-3w): After separation by silica gel chromatography, a colorless oil was obtained in 72% yield (17.2 mg, eluent: DCM / MeOH = 30 / 1).

[0080] 1 H NMR (400 MHz, Methanol- d 4) δ7.42 – 7.33 (m, 2H), 6.94 – 6.85 (m,2H), 4.65 (d, J = 6.8 Hz, 1H), 4.08 – 4.00 (m, 1H), 3.94 (d, J = 4.5 Hz, 1H), 3.85 (t,J = 6.4 Hz, 1H), 3.78 (d, J = 1.7 Hz, 3H), 3.77 (s, 1H), 3.71 (dd, J =12.0, 4.9 Hz, 1H). 13 C NMR (100 MHz, Methanol- d 4)δ160.9, 133.7, 128.8, 114.7, 86.3, 85.3,78.9, 73.0, 63.7, 55.7. Example 23 The difference from Example 1 is that "all-hydroxyl o-alkynylphenyl thioglycoside" was replaced with "unprotected o-alkynylphenyl thiomaltoglycoside", resulting in the corresponding product compound (3-3x).

[0081] Compound (3-3x): After separation by silica gel chromatography, a colorless oil (33.2 mg, eluent: DCM / MeOH = 10 / 1) was obtained in 76% yield.

[0082] 1 H NMR (400 MHz, Methanol- d 4) δ7.34 (d, J = 8.7 Hz, 2H), 6.89 (d, J =8.7 Hz, 2H), 5.21 (d, J = 3.7 Hz, 1H), 4.10 (d, J = 9.5 Hz, 1H), 3.93 – 3.80(m, 3H), 3.78 (s, 3H), 3.76 – 3.62 (m, 5H), 3.52 – 3.39 (m, 3H), 3.28 (d, J =9.3 Hz, 1H). 13 C NMR (100 MHz, Methanol- d 4)δ161.0, 132.7, 130.2, 114.5, 103.0,83.2, 81.7, 80.7, 79.6, 75.9, 75.1, 74.8, 74.3, 71.5, 62.7, 62.6, 55.7. Example 24 This embodiment provides a method for synthesizing canagliflozin, the synthetic route is as follows: Figure 7 As shown, the specific synthesis method is as follows: Unprotected o-alkynylphenyl thioglycoside, 2-(4-fluorophenyl)-5-[(5-iodo-2-methylphenyl)methyl]thiophene, ruthenium chloride hexahydrate of terpyridine, nickel(II) 2-methoxyethyl ether complex, 4,4',4''-tritert-butyl-2,2',6',2''-terpyridine, triethylenediamine, and sodium cyclopropane sulfinate were added to the reaction vessel, nitrogen gas was purged, and then ultra-dry DMF was added as solvent. The reaction was carried out for 36 hours.

[0083] 1 H NMR (400 MHz, Methanol- d 4) δ7.52 (dd, J = 7.9, 4.6 Hz, 2H), 7.31 (s,1H), 7.24 (d, J = 7.9 Hz, 1H), 7.16 (d, J = 7.7 Hz, 1H), 7.13 – 6.99 (m, 3H), 6.70 (d, J = 3.2 Hz, 1H), 4.14 (s, 2H), 4.11 (d, J = 9.4 Hz, 1H), 3.88 (d, J =11.9 Hz, 1H), 3.74 – 3.66 (m, 1H), 3.52 – 3.36 (m, 4H), 2.30 (s, 3H). 13 C NMR (100 MHz, Methanol- d 4)δ164.6, 162.2, 145.1, 142.5, 139.2,138.7, 137.2, 132.5, 132.4, 131.2, 130.4, 128.1, 128.1, 127.5, 127.1, 123.9,116.7, 116.5, 83.5, 82.2, 79.8, 76.4, 72.0, 63.2, 34.9, 19.3. Example 25 This embodiment provides a method for synthesizing dapagliflozin, the synthetic route is as follows: Figure 8 As shown, the specific synthesis method is as follows: Unprotected o-alkynylphenyl thioglycoside, 1-chloro-2-(4-ethoxybenzyl)-4-iodobenzene, ruthenium chloride hexahydrate of terpyridine, nickel(II) 2-methoxyethyl ether complex, 4,4',4''-tritert-butyl-2,2',6',2''-terpyridine, triethylenediamine, and sodium cyclopropane sulfinate were added to the reaction vessel, nitrogen gas was purged, and then ultra-dry DMF was added as a solvent. The reaction was carried out for 36 hours.

[0084] 1 H NMR (400 MHz, Methanol- d 4) δ7.43 – 7.21 (m, 3H), 7.09 (d, J = 8.0Hz, 2H), 6.79 (d, J = 8.1 Hz, 2H), 4.13 – 4.06 (m, 1H), 4.05 – 3.94 (m, 3H), 3.87 (d, J = 12.0 Hz, 1H), 3.69 (dd, J = 12.6, 4.1 Hz, 1H), 3.47 – 3.42 (m,1H), 3.39 (d, J = 7.0 Hz, 2H), 3.28 (d, J = 9.0 Hz, 2H), 1.42 – 1.30 (m, 3H). 13 C NMR (100 MHz, Methanol- d 4)δ158.8, 140.0, 139.9, 134.4, 132.9,131.9, 130.8, 130.1, 128.2, 115.4, 82.9, 82.2, 79.7, 76.4, 71.8, 64.4, 63.1,49.6, 49.4, 49.2, 49.0, 48.8, 48.6, 48.4, 39.2, 15.2. The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for synthesizing an unprotected aryl C-glycoside, characterized in that, The synthesis method includes: reacting an unprotected glycosyl donor, acceptor, photocatalyst, transition metal catalyst, ligand, base, free radical precursor and solvent under inert gas protection to obtain aryl C-glycoside; The unprotected glycosyl donor is at least one of the following: unprotected o-alkynylphenylthioglucoside, unprotected o-alkynylphenylthiomannoside, unprotected o-alkynylphenylthiogalactoside, unprotected o-alkynylphenylthio(2-acetamino)glucoside, unprotected o-alkynylphenylthio(2-acetamino)galactoside, unprotected o-alkynylphenylthiorhamnoside, unprotected o-alkynylphenylthiofucoside, unprotected o-alkynylphenylthioxyloside, unprotected o-alkynylphenylthioriboside, and unprotected o-alkynylphenylthiomaltobiside. The acceptor is at least one of 4-methoxyiodobenzene, 3-methoxyiodobenzene, 2-methoxyiodobenzene, 4-tert-butyliodobenzene, 4-trifluoromethyliodobenzene, ethyl p-iodobenzoate, 4-iodobiphenyl, 4-chloroiodobenzene, 4-bromoiodobenzene, 2-iodopyrazine, 3-iodobenzothiophene, and 5-iodo-1H-indole-1-carboxylic acid tert-butyl ester; The photocatalyst is at least one of the following: tripyridine ruthenium chloride hexahydrate, tris(1,10-phenanthroline)ruthenium(II) bis(hexafluorophosphate), tris(2,2'-bipyridine)ruthenium di(tetrafluoroborate), di[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium di(hexafluorophosphate), planar-tris(2-phenylpyridine)iridium, and 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile; The transition metal catalyst is at least one of ethylene glycol dimethyl ether nickel bromide, nickel(II) bromide 2-methoxyethyl ether complex, nickel(II) trifluoromethanesulfonate, and bis(triphenylphosphine) nickel chloride; The ligand is at least one of L1 to L6: ； The base is at least one of triethylenediamine, tetramethylguanidine, and triethylamine; The free radical precursor is sodium cyclopropane sulfinate.

2. The synthesis method according to claim 1, characterized in that, The solvent is DMF.

3. The synthesis method according to claim 1, characterized in that, The molar ratio of the unprotected glycosyl donor, acceptor, photocatalyst, transition metal catalyst, ligand, base, and free radical precursor is 1:1~2:0.01:0.05~0.15:0.1~0.14:1.5~2.5:2.5~3.

5.

4. The synthesis method according to claim 1, characterized in that, The reaction conditions include: 10 W 455 nm blue light irradiation, room temperature reaction for 12 to 48 hours.

5. The use of the aryl C-glycoside obtained by the synthetic method according to any one of claims 1 to 4 in the synthesis of SGLT2 inhibitor drugs.

6. The application according to claim 5, characterized in that, The SGLT2 inhibitors include at least one of canagliflozin, dapagliflozin, and empagliflozin.

7. A method for the continuous synthesis of empagliflozin, characterized in that, The method includes the following steps: Unprotected o-alkynylphenyl thioglycoside, (3S)-3-[4-[(2-chloro-5-iodophenyl)methyl]phenoxy]tetrahydrofuran, ruthenium tripyridine chloride hexahydrate, nickel(II) 2-methoxyethyl ether complex, 4,4',4''-tritert-butyl-2,2',6',2''-terpyridine, triethylenediamine, and sodium cyclopropane sulfinate were added to the reaction vessel, nitrogen gas was purged, and then ultra-dry DMSO was added as a solvent to obtain the reaction solution. The reaction solution was pumped into the flow photoreactor at a flow rate of 0.8 mL / min, and the reaction solution was kept in the microchannel reaction plate for 2 hours at 25 °C and under the illumination of a 455 nm LED lamp. After the reaction was completed, the product was diluted with ethyl acetate, washed with saturated sodium chloride solution, concentrated, and purified by column chromatography to obtain empagliflozin.

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