A kind of 3-indole-deoxycarbonyl glycoside and preparation method thereof

Abstract

The present invention discloses a 3-indole-deoxycarbon glycoside and a preparation method thereof. The present invention uses an easily synthesized olefin sugar donor and an indole derivative as raw materials, and catalyzes the indole C-3 glycosylation reaction with an inexpensive metal catalyst to construct the 3-indole-deoxycarbon glycoside. The preparation method can prepare the 3-indole-deoxycarbon glycoside with high regioselectivity and stereoselectivity. The preparation method of the present invention has the advantages of readily available raw materials, mild reaction conditions, wide substrate applicability, and simple operation. The prepared 3-indole-deoxycarbon glycoside has potential biological activity and can be widely used as a fine chemical intermediate in various organic reactions and the synthesis of drugs for the treatment of type 2 diabetes, and has considerable application value.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis and medicine, and particularly relates to 3-indole-deoxycarbonyl glycoside and a preparation method thereof. Background Art

[0002] C-glycoside structural units are widely present in natural products and drug molecules. They not only have structures similar to O-glycosides and N-glycosides, but also have better chemical and metabolic stability. They have shown unique advantages in the research and development of new carbohydrate drugs.

[0003] Indole-C-glycosides are similar in structure to natural N-nucleosides and have shown great potential in anticancer and antiviral activities, which have attracted widespread attention from chemists and biologists. In particular, 3-indole-C-glycosides are inhibitors of sodium-dependent glucose cotransporter SGLT2, such as 3-indole-C-glycosides (its structural formula is shown in Figure 7 ), showing great potential in the treatment of type II diabetes (EP Appl EP1813611A1, 2007; Eur.J.Med.Chem.2012, 55, 32-38; Eur.J.Med.Chem.2018, 152, 436-488). As an important class of 2-deoxy-C-glycoside derivatives, 3-indole-deoxycarbon glycosides have unique structural characteristics and can be used as a new type of potential SGLT2 inhibitor for the treatment of type II diabetes. However, the current synthesis methods of 3-indole-deoxycarbon glycosides still have many limitations, such as the use of precious metal catalysis, pre-functionalization of glycosyl donors, and limited substrate applicability. Therefore, the development of efficient and step-economical synthesis methods for the construction of 3-indole-deoxycarbon glycosides is of great significance and application value. Summary of the Invention

[0004] In view of the problems existing in the prior art, the object of the present invention is to provide a 3-indole-deoxycarbon glycoside and a preparation method thereof, which has the characteristics of high regioselectivity, high stereoselectivity and a wide range of substrate applicability.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] The first aspect of the present invention provides a method for preparing 3-indole-deoxycarbon glycoside, the structural formula of which is shown in the following formula III:

[0007]

[0008] Wherein, R1 is selected from H, F, Cl, Br, CH3, OCH3; R is selected from H, CH3, benzyl, benzoyl, benzenesulfonyl, p-toluenesulfonyl, tert-butoxycarbonyl, pyridine, pyrimidine, 3-methylpyridine, 3-methoxypyridine or 5-methylpyridine; P represents a protecting group selected from benzyl, methyl, p-methoxybenzyl or propargyl.

[0009] Preferably, the 3-indole-deoxycarbon glycoside is a β-isomer or an α-isomer.

[0010] A second aspect of the present invention provides a method for preparing the above-mentioned 3-indole-deoxycarbon glycoside, comprising the following steps: adding a glycalol donor represented by Formula I, an indole substrate represented by Formula II, a metal catalyst, a reducing agent, and an additive to an organic solvent under a protective gas atmosphere, stirring the mixture for reaction, and purifying the mixture after completion of the reaction to obtain the 3-indole-deoxycarbon glycoside. The synthetic route is as follows:

[0011]

[0012] Wherein, R1 is located at the C4, C5 and C6 positions of the indole substrate and is selected from H, fluorine, chlorine, bromine, methyl or methoxy; R is selected from any one of H, CH3, benzyl, benzoyl, benzenesulfonyl, p-toluenesulfonyl, tert-butyloxycarbonyl, pyridine, pyrimidine, 3-methylpyridine, 3-methoxypyridine or 5-methylpyridine; P represents a protecting group of the glycalol donor and is selected from benzyl, methyl, p-methoxybenzyl or propargyl.

[0013] Preferably, the molar ratio of the glycal donor to the indole substrate is 1:0.5-1.5, and the glycal donor is any one of galactal, glucal or rhamnal.

[0014] Preferably, the molar ratio of the metal catalyst to the glycal donor is 0.01 to 0.2:1; the metal catalyst is any one of scandium trifluoromethanesulfonate, copper trifluoromethanesulfonate, zinc trifluoromethanesulfonate, iron trifluoromethanesulfonate, cobalt acetate, cobalt chloride, cobalt bromide or cobalt (II) acetylacetonate, more preferably cobalt bromide;

[0015] Preferably, the molar ratio of the additive to the metal catalyst is 0 to 3:1, more preferably 1:1; the additive is sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (NaBArF4), and its structural formula is shown in Formula IV:

[0016]

[0017] Preferably, the molar ratio of the reducing agent to the metal catalyst is 0 to 3:1, more preferably 3:1; the reducing agent is zinc powder or manganese powder, more preferably manganese powder.

[0018] Preferably, the organic solvent is selected from one or a combination of two or more of N,N-dimethylformamide (DMF), tetrahydrofuran (THF), dichloromethane (DCM), toluene, 1,2-dichloroethane (DCE), trifluorotoluene or 1,4-dioxane, more preferably 1,2-dichloroethane (DCE).

[0019] Preferably, the amount of the organic solvent added satisfies the concentration of the glycal donor to be 0.01 to 0.5 mol / s.

[0020] Preferably, the reaction temperature is 10° C. to 60° C., more preferably 40° C.; the reaction time is 12 to 48 h, more preferably 24 h.

[0021] Preferably, the protective gas is nitrogen or argon, more preferably argon.

[0022] Preferably, the purification treatment includes: filtration, reduced pressure distillation, column chromatography separation or silica gel plate (Pre-TLC) separation and purification.

[0023] Preferably, the developing solvent used for column chromatography separation and purification is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 1 to 10:1.

[0024] Preferably, the eluent used for separation and purification on the silica gel plate is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 1 to 20:1.

[0025] The third aspect of the present invention provides the use of the above-mentioned 3-indole-deoxycarbon glycoside in the preparation of a drug for treating type II diabetes.

[0026] The present invention has the following beneficial effects:

[0027] (1) The present invention uses readily synthesizable glycosylal donors and indole derivatives (indole substrates) as raw materials and catalyzes the C-3 glycosylation reaction of indole with an inexpensive metal catalyst to construct 3-indole-deoxycarbonyl glycosides. This preparation method features mild reaction conditions, simple operation, good functional group compatibility, and broad substrate applicability.

[0028] (2) The 3-indole-deoxycarbonyl glycoside prepared by the present invention has potential biological activity and can be widely used as a fine chemical intermediate in various organic reactions and the synthesis of drugs for treating type II diabetes, and has considerable application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0030] Figure 1 The synthetic route of the 3-indole-deoxycarbon glycoside of the present invention is as follows;

[0031] Figure 2 is the structural formula of the glycal donor involved in Examples 1-22;

[0032] Figure 3 is the structural formula of the indole substrate involved in Examples 1-22;

[0033] Figure 4 is the structural formula of 3-indole-deoxycarbonyl glycoside obtained in Example 1-22;

[0034] Figure 5 1H spectrum of 3-indole-deoxycarbonyl glycoside 3a obtained in Example 1;

[0035] Figure 6 is the carbon spectrum of 3-indole-deoxycarbonyl glycoside 3a obtained in Example 1;

[0036] Figure 7 is the structural formula of a 3-indole-carbon glycoside having SGLT2 inhibitory activity;

[0037] Figure 8 It is the general structural formula of the 3-indole-deoxycarbon glycoside of the present invention. DETAILED DESCRIPTION

[0038] In the following description, specific details such as specific system structures and technologies are provided for the purpose of illustration rather than limitation to facilitate a thorough understanding of the embodiments of the present invention. However, it should be clear to those skilled in the art that the present invention may also be implemented in other embodiments without these specific details.

[0039] Reference Figure 1-7 , 3-indole-carbon glycoside (structural formula see Figure 8 ).

[0040] Example 1

[0041]

[0042] Under inert gas, indole substrate 1a (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask. After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3a.

[0043] Characterization results of compound 3a: 1 H NMR(500MHz,Chloroform-d)δ8.08(dd,J=4.7,1.4Hz,1H),7.74(dt,J=7.8,1.0Hz,1H),7.57-7.45 (m,2H),7.36-7.31(m,2H),7.30-7.16(m,16H),7.03(ddd,J=8.1,7.0,1.0Hz,1H),4.95(d,J=11.7 Hz,1H),4.73(dd,J=11.6,2.2Hz,1H),4.66-4.56(m,3H),4.46-4.36(m,2H),3.97-3.92(m,1H),3. 80-3.69(m,5H),3.63(qd,J=9.2,6.4Hz,2H),2.58(q,J=12.0Hz,1H),2.17(dt,J=11.7,2.3Hz,1H).

[0044] 13 C NMR (126MHz, CDCl3) δ148.41,142.12,139.83,139.28,138.51,138.15,1 36.61,128.40,128.36,128.33,128.29,128.09,127.89,127.61,127.51, 127.31,127.23,125.14,122.54,122.02,120.50,120.15,120.10,117.93 ,112.71,78.84,74.16,73.50,72.67,72.29,70.05,69.65,55.73,32.39.

[0045] HRMS (ESI-TOF) Calcd for C 41 H 40 N2O5[M+Na] + :663.2835,found:663.2841.

[0046] Example 2

[0047]

[0048] Under inert gas, indole substrate 1b (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask. After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3b.

[0049] Characterization results of compound 3b: 1 H NMR(500MHz,Chloroform-d)δ8.15(d,J=4.9Hz,1H),7.67-7.56(m,2H),7.50(dd ,J=9.5,2.6Hz,1H),7.43-7.22(m,17H),6.94(td,J=9.1,2.6Hz,1H),5.03(d,J= 11.7Hz,1H),4.80-4.60(m,4H),4.52(d,J=11.7Hz,1H),4.46(d,J=11.7Hz,1H), 4.05-3.99(m,1H),3.92-3.61(m,7H),2.63(q,J=12.0Hz,1H),2.25-2.17(m,1H).

[0050] 13 C NMR (126MHz, CDCl3) δ157.34,148.23,141.95,139.86,139.24,138.50,1 38.13,133.15,128.47,128.41,128.18,127.98,127.90,127.70,127.61, 127.38,127.31,126.58,122.12,120.20,117.90,113.79,110.91,110.70 ,105.32,78.74,74.25,73.59,72.61,72.21,70.16,69.68,55.84,32.30.

[0051] HRMS (ESI-TOF) Calcd for C 41 H 39 FN2O5[M+Na] +:681.2741,found:681.2749.

[0052] Example 3

[0053]

[0054] Under inert gas, indole substrate 1c (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask. After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3c.

[0055] Characterization results of compound 3c: 1 H NMR(500MHz,Chloroform-d)δ8.16(dd,J=4.8,1.4Hz,1H),7.82(d,J=2.0Hz,1H),7.61(s,1H ),7.56(d,J=8.8Hz,1H),7.43-7.25(m,17H),7.15(dd,J=8.8,2.1Hz,1H),5.04(d,J=11.7Hz, 1H),4.80-4.65(m,4H),4.53(d,J=11.7Hz,1H),4.45(d,J=11.8Hz,1H),4.08-4.01(m,1H),3 .84(s,3H),3.82-3.76(m,2H),3.75-3.67(m,2H),2.63(q,J=12.0Hz,1H),2.23-2.18(m,1H).

[0056] 13 C NMR (126MHz, CDCl3) δ148.32,141.74,139.91,139.25,138.49,138.14,1 35.06,128.73,128.47,128.41,128.20,127.98,127.80,127.68,127.61, 127.39,127.25,126.37,126.24,122.89,122.33,120.23,119.80,117.61 ,114.00,78.72,74.29,73.59,72.70,72.15,70.18,69.65,55.82,32.42.

[0057] HRMS (ESI-TOF) Calcd for C 41 H 39 ClN2O5[M+Na] + :697.2445,found:697.2444.

[0058] Example 4

[0059]

[0060] Under inert gas, indole substrate 1d (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask. After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3d.

[0061] Characterization results of compound 3d: 1 H NMR(500MHz,Chloroform-d)δ8.15(dd,J=4.7,1.5Hz,1H),7.97(d,J=1.9Hz,1H),7 .59(s,1H),7.50(d,J=8.7Hz,1H),7.43-7.25(m,18H),5.04(d,J=11.8Hz,1H),4.7 9-4.63(m,4H),4.53(d,J=11.8Hz,1H),4.45(d,J=11.8Hz,1H),4.04-4.00(m,1H), 3.84(s,3H),3.82-3.75(m,2H),3.75-3.66(m,2H),2.24-2.16(m,1H),2.05(s,1H).

[0062] 13 C NMR (126MHz, CDCl3) δ148.35,141.69,139.93,139.25,138.48,138.13,1 35.35,129.32,128.47,128.41,128.22,127.99,127.81,127.68,127.61, 127.39,127.25,126.25,125.47,122.83,122.39,120.23,117.52,114.41 ,113.96,78.71,74.31,73.59,72.72,72.12,70.18,69.63,55.82,32.44.

[0063] HRMS (ESI-TOF) Calcd for C 41 H 39 BrN2O5[M+Na] + :741.1940,found:741.1946.

[0064] Example 5

[0065]

[0066] Under inert gas protection, indole substrate 1e (0.11 mmol), galenol 2a (0.1 mmol), cobalt bromide (10 mol%), NaBAr F 4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were stirred to dissolve, and the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction solution was filtered and evaporated under reduced pressure. The crude product was separated and purified on a silica gel plate (eluent: a mixture of petroleum ether and ethyl acetate in a 5:1 volume ratio) to afford compound 3e.

[0067] Characterization results of compound 3e: 1 H NMR(500MHz,Chloroform-d)δ8.07(dd,J=4.7,1.4Hz,1H),7.54-7.10(m,20H),6 .93(dd,J=8.4,1.7Hz,1H),4.98(d,J=11.7Hz,1H),4.69(dd,J=11.7,2.2Hz,1H), 4.66-4.52(m,3H),4.46(d,J=11.8Hz,1H),4.38(d,J=11.7Hz,1H),3.99-3.92(m ,1H),3.85-3.57(m,7H),2.61(d,J=12.1Hz,1H),2.30(s,3H),2.18-2.07(m,1H).

[0068] 13C NMR (126MHz, CDCl3) δ147.28,141.31,138.84,138.41,137.56,137.19,134 .02,128.76,127.41,127.34,127.10,126.89,126.78,126.73,126.61,126 .51,126.33,126.17,124.24,123.11,120.73,119.07,118.86,116.60,111.53,76.62,73.20,72.52,71.82,71.43,69.05,68.64,54.74,31.46,20.44.

[0069] HRMS (ESI-TOF) Calcd for C 42 H 42 N2O5[M+Na] + :677.2991,found:677.3001.

[0070] Example 6

[0071]

[0072] Under inert gas, a reaction flask was added with indole substrate 1f (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL). After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3f.

[0073] Characterization results of compound 3f: 11H NMR (500 MHz, Chloroform-d) δ 8.08 (dd, J = 4.7, 1.4 Hz, 1H), 7.53 - 7.49 (m, 2H), 7.35 - 7.31 (m, 5H), 7.31 - 7.28 (m, 3H), 7.27 - 7.24 (m, 6H), 7.21 (dd, J = 6.4, 3.8 Hz, 3H), 7.14 (dd, J = 8.2, 4.7 Hz, 1H), 6.76 (dd, J = 9.0, 2.6 Hz, 1H), 4.98 (d, J = 11.4 Hz, 1H), 4.70 (dd, J = 11.6, 2.3 Hz, 1H), 4.64 - 4.60 (m, 3H), 4.48 (d, J = 11.7 Hz, 1H), 4.42 (d, J = 11.8 Hz, 1H), 4.00 - 3.97 (m, 1H), 3.77 (s, 3H), 3.75 - 3.72 (m, 2H), 3.70 (d, J = 7.1 Hz, 1H), 3.67 - 3.64 (m, 1H), 3.53 (s, 3H), 2.65 (q, J = 12.0 Hz, 1H), 2.13 (dq, J = 12.7, 2.3 Hz, 1H).

[0074] 13 13C NMR (126 MHz, CDCl3) δ 153.51, 147.09, 141.26, 138.79, 138.29, 137.54, 137.11, 130.76, 127.42, 127.36, 127.10, 127.03, 126.93, 126.66, 126.53, 126.33, 126.31, 124.52, 120.61, 119.07, 116.73, 112.78, 111.59, 101.00, 76.47, 73.47, 72.53, 71.91, 71.54, 69.05, 68.61, 54.76, 54.42, 31.40.

[0075] HRMS (ESI-TOF) Calcd for C 42 H 42 N2O6 [M+Na] + : 693.2941, found: 693.2949.

[0076] Example 7

[0077]

[0078] Under inert gas, a reaction flask was added with 1 g (0.11 mmol) of the indole substrate, glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL). After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to yield compound 3g.

[0079] Characterization results of compound 3g: 1 H NMR (500MHz, CDCl3) δ8.11 (dd, J=4.7, 1.4Hz, 1H), 7.57 (s, 1H), 7.37-7.14 (m, 18H) ,7.05(td,J=8.1,5.2Hz,1H),6.76(dd,J=10.8,7.8Hz,1H),4.97-4.87(m,2H),4.69 -4.54(m,3H),4.49(d,J=11.8Hz,1H),4.41(d,J=11.7Hz,1H),3.96(dd,J=2.7,1.2H z,1H),3.84-3.70(m,5H),3.66(qd,J=9.3,6.5Hz,2H),2.35(td,J=8.2,2.8Hz,2H).

[0080] 13 C NMR (126MHz, CDCl3) δ148.61,141.75,139.88,139.30,138.58,138.26,128.45,128.36,128.11,128.08,127.94,127.63,127.55,127.40,127. 29,125.72,122.91,122.85,122.63,120.19,116.65,108.90,106.08,1 05.92,79.06,74.30,73.47,72.81,72.43,70.16,69.49,55.81,29.72.

[0081] HRMS (ESI-TOF) Calcd for C 41 H 39 FN2O5[M+Na] + :681.2741,found:681.2749.

[0082] Example 8

[0083]

[0084] Under inert gas, a reaction flask was added with indole substrate 1h (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL). After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3h.

[0085] Characterization results of compound 3h: 1 H NMR (500MHz, CDCl3) δ8.10 (dd, J=4.8, 1.4Hz, 1H), 7.70 (d, J=7.9Hz, 1H), 7.55-7.46 (m, 2H), 7.32-7.12 (m, 17H), 7.07 (t, J=7.5Hz, 1H), 4. 91(d,J=10.8Hz,1H),4.79-4.40(m,6H),3.98-3.69(m,6H),3.69-3.54(m,2H),2.51(ddd,J=12.8,5.0,2.0Hz,1H),2.06(q,J=11.9Hz,1H).

[0086] 13 C NMR (126MHz, CDCl3) δ148.74,141.53,139.94,139.36,138.60,138.25,1 37.84,128.45,128.36,128.09,128.04,127.94,127.63,127.56,127.41, 127.25,127.08,125.80,124.59,122.85,122.80,121.78,120.23,117.86 ,111.44,79.05,74.34,73.51,72.82,71.54,70.13,69.32,55.81,32.97.

[0087] HRMS (ESI-TOF) Calcd for C 41 H 39 ClN2O5[M+Na] + :697.2445,found:697.2455.

[0088] Example 9

[0089]

[0090] Under inert gas, a reaction flask was added with indole substrate 1i (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL). After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3i.

[0091] Characterization results of compound 3i: 1 H NMR (500MHz, CDCl3) δ8.15 (dd, J=4.8, 1.4Hz, 1H), 7.82 (d, J=2.0Hz, 1H), 7.60 (s, 1H), 7.55(d,J=8.8Hz,1H),7.43-7.21(m,17H),7.14(dd,J=8.8,2.1Hz,1H),5.04(d,J=11.7 Hz,1H),4.78-4.63(m,4H),4.58-4.41(m,2H),4.05-4.00(m,1H),3.84(s,3H),3.82-3 .74(m,2H),3.74-3.65(m,2H),2.62(q,J=12.0Hz,1H),2.27-2.13(m,1H),1.58(s,3H).

[0092] 13 C NMR (126MHz, CDCl3) δ148.80,142.08,139.94,139.23,138.54,138.16,1 36.99,130.87,128.50,128.37,128.11,128.04,127.92,127.66,127.63, 127.41,127.30,126.77,126.20,122.48,122.46,122.37,120.11,118.05 ,110.33,79.22,74.32,73.61,72.66,71.93,70.21,69.74,31.65,19.88.

[0093] HRMS (ESI-TOF) Calcd for C 42 H 42 N2O5[M+Na] + :677.2991,found:677.3004.

[0094] Example 10

[0095]

[0096] Under inert gas, indole substrate 1j (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask. After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3j.

[0097] Characterization results of compound 3j: 1 H NMR (500MHz, CDCl3) δ8.17-8.12(m,1H),7.73(dd,J=8.7,5.4Hz,1H),7.56(d,J=3.7Hz,1H),7 .43-7.20(m,18H),6.84(td,J=9.1,2.5Hz,1H),5.02(dd,J=11.6,3.7Hz,1H),4.76(dd,J=11.6 ,2.4Hz,1H),4.72-4.64(m,3H),4.54-4.43(m,2H),4.02(d,J=2.5Hz,1H),3.84(d,J=3.8Hz,3H ),3.81-3.75(m,2H),3.74-3.65(m,2H),2.63(q,J=12.0Hz,1H),2.21(dt,J=12.6,3.3Hz,1H).

[0098] 13 C NMR (126MHz, CDCl3) δ148.25,141.84,139.89,139.28,138.51,138.17,1 36.79,136.68,128.47,128.41,128.16,127.96,127.94,127.70,127.60, 127.37,127.34,125.42,124.11,122.26,121.04,120.23,118.02,109.2 3,99.53,78.78,74.23,73.57,72.63,72.27,70.15,69.70,55.83,29.72.

[0099] HRMS (ESI-TOF) Calcd for C 41 H 39 FN2O5[M+Na] +:681.2741,found:681.2745.

[0100] Example 11

[0101]

[0102] Under inert gas, indole substrate 1k (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask. After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3k.

[0103] Characterization results of compound 3k: 1 H NMR(500MHz, CDCl3)δ8.10(dd,J=4.7,1.4Hz,1H),7.68(d,J=8.4Hz,1H),7.60(d,J=1.8Hz,1H), 7.51(s,1H),7.37-7.33(m,2H),7.32-7.17(m,15H),7.01(dd,J=8.5,1.9Hz,1H),4.97(d,J=11. 7Hz,1H),4.71(dd,J=11.6,2.3Hz,1H),4.67-4.57(m,3H),4.49-4.37(m,2H),4.02-3.94(m,1H) ,3.78(s,3H),3.75-3.70(m,2H),3.68-3.59(m,2H),2.56(q,J=12.0Hz,1H),2.22-2.08(m,1H).

[0104] 13 C NMR (126MHz, CDCl3) δ148.32,141.65,139.94,139.26,138.51,138.16,1 36.99,128.59,128.49,128.43,128.19,127.98,127.96,127.72,127.63, 127.39,127.37,126.22,125.75,122.42,121.24,120.30,118.01,112.9 7,78.76,77.70,74.25,73.59,72.62,72.18,70.17,69.71,55.85,32.44.

[0105] HRMS (ESI-TOF) Calcd for C 41 H 39 ClN2O5[M+Na] + :697.2445,found:697.2446.

[0106] Example 12

[0107]

[0108] Under inert gas, indole substrate 1l (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask. After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3l.

[0109] Characterization results of compound 3l: 1 H NMR (500MHz, CDCl3) δ8.12(dd,J=4.7,1.4Hz,1H),7.63(d,J=8.0Hz,1H),7.46(s,1H),7.38(s,1H),7.36(d,J=7.2Hz ,2H),7.33-7.20(m,14H),7.17(dd,J=8.1,4.7Hz,1H),6.89(dd,J=8.1,1.5Hz,1H),4.98(d,J=11.7Hz,1H),4.72(dd, J=11.7,2.2Hz,1H),4.65(d,J=11.7Hz,1H),4.61(s,2H),4.47(d,J=11.8Hz,1H),4.40(d,J=11.7Hz,1H),3.97(d,J= 2.4Hz,1H),3.80-3.71(m,5H),3.70-3.62(m,2H),2.59(q,J=11.9Hz,1H),2.38(s,3H),2.18(dt,J=12.4,3.0Hz,1H). 13C NMR (126MHz, CDCl3) δ148.50,142.38,139.87,139.38,138.60,138.24,137 .07,132.39,128.45,128.39,128.14,127.96,127.94,127.66,127.56,127 .37,127.27,125.49,124.62,122.30,121.89,120.19,119.77,117.86,112.63,78.94,74.21,73.57,72.74,72.43,70.11,69.71,55.82,32.48,21.97.

[0110] HRMS (ESI-TOF) Calcd for C 42 H 42 N2O5[M+Na] + :677.2991,found:677.3009.

[0111] Example 13

[0112]

[0113] Under inert gas, a reaction flask was added with indole substrate 1m (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL). After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3m.

[0114] Characterization results of compound 3m: 11H NMR (500 MHz, CDCl3) δ 8.09 (dd, J = 4.7, 1.5 Hz, 1H), 7.61 (d, J = 8.7 Hz, 1H), 7.40 (s, 1H), 7.35 - 7.32 (m, 2H), 7.31 - 7.21 (m, 12H), 7.18 (s, 2H), 7.17 - 7.15 (m, 1H), 7.09 (d, J = 2.3 Hz, 1H), 6.69 (dd, J = 8.6, 2.3 Hz, 1H), 4.95 (d, J = 11.7 Hz, 1H), 4.71 - 4.57 (m, 4H), 4.44 (d, J = 11.8 Hz, 1H), 4.38 (d, J = 11.8 Hz, 1H), 3.96 - 3.92 (m, 1H), 3.77 (s, 3H), 3.73 (s, 3H), 3.72 - 3.58 (m, 4H), 2.56 (q, J = 12.0 Hz, 1H), 2.18 - 2.12 (m, 1H).

[0115] 13 13C NMR (126 MHz, CDCl3) δ 156.78, 148.41, 142.33, 139.88, 139.35, 138.58, 138.23, 137.44, 128.45, 128.39, 128.13, 127.94, 127.66, 127.56, 127.36, 127.27, 124.10, 122.00, 121.96, 120.77, 120.21, 117.98, 110.22, 96.81, 78.89, 74.19, 73.56, 72.70, 72.43, 70.10, 69.72, 55.79, 55.68, 32.46.

[0116] HRMS (ESI - TOF) Calcd for C 42 H 42 N2O6 [M + Na] + : 693.2941, found: 693.2948.

[0117] Example 14

[0118]

[0119] Under inert gas, indole substrate 1a (0.11 mmol), glycal 2b (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask. After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3n.

[0120] Characterization results of compound 3n: 1 H NMR (500MHz, CDCl3) δ8.17 (dd, J=5.0, 1.5Hz, 1H), 7.77 (d, J=7.5Hz, 1H), 7.63 (d ,J=8.0Hz,1H),7.60(s,1H),7.40(dd,J=13.0,6.5Hz,1H),7.25-7.14(m,3H),4. 81(dd,J=11.5,1.5Hz,1H),3.84(s,3H),3.76-3.66(m,4H),3.62(s,3H),3.57-3 .53(m,1H),3.48(s,3H),3.42(s,3H),2.43(q,J=12.0Hz,1H),2.22-2.19(m,1H).

[0121] 13 C NMR (125MHz, CDCl3) δ148.45,142.20,139.88,136.60,127.64,125.29,122.57,122.03,120.55,120.12 ,119.88,117.85,112.78,80.73,77.50,74.31,72.26,71.73,61.00,59.24,56.18,55.78,32.11,29.72.

[0122] HRMS (ESI-TOF) Calcd for C 23 H 28 N2O5[M+Na] + :435.1896,found:435.1914.

[0123] Example 15

[0124]

[0125] Under inert gas, indole substrate 1a (0.11 mmol), glycal 2c (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask and stirred to dissolve. The reaction was then placed in a heating block at 40°C for 24 h. The reaction solution was filtered and evaporated under reduced pressure. The crude product was separated and purified on a silica gel plate (the eluent was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain compound 3o.

[0126] Characterization results of compound 3o: 1 H NMR(500MHz, CDCl3)δ8.11(dd,J=4.7,1.4Hz,1H),7.77(dt,J=7.9,1.0Hz,1H),7.59-7.52(m,2H),7.39-7.35(m, 2H),7.32-7.15(m,11H),7.06(ddd,J=8.1,7.0,1.0Hz,1H),4.91(d,J=11.7Hz,1H),4.79(dd,J=11.6,2.2Hz,1H) ,4.62(d,J=11.7Hz,1H),4.48(d,J=11.8Hz,1H),4.41(d,J=11.7Hz,1H),4.24-4.13(m,2H),3.96-3.89(m,2H),3 .77(s,4H),3.70-3.62(m,2H),2.52(q,J=11.8Hz,1H),2.39(t,J=2.4Hz,1H),2.17(ddt,J=12.1,4.0,1.8Hz,1H).

[0127] 13 C NMR (126MHz, CDCl3) δ148.56,142.27,140.00,139.35,138.29,136.78,128.50,128.25,128.04,128.02,127.78,127.71,127.42,125 .29,122.72,122.18,120.67,120.31,120.27,118.00,112.89,80.09,78.22,77.76,73.65,72.69,72.43,69.70,55.89,55.41,32.21.

[0128] HRMS (ESI-TOF) Calcd for C 37 H 36 N2O5[M+Na] +:611.2522,found:611.2532.

[0129] Example 16

[0130]

[0131] Under inert gas protection, indole substrate 1a (0.11 mmol), glycal 2d (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv) and 1,2-dichloroethane (DCE) (1 mL) were added to the reaction flask and stirred to dissolve. The reaction was placed in a heating block at 40°C for 24 h. The reaction solution was filtered and evaporated under reduced pressure. The crude product was separated and purified on a silica gel plate (the eluent was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain compound 3p.

[0132] Characterization results of compound 3p: 1 H NMR (500MHz, CDCl3) δ8.17 (dd, J=4.7, 1.4Hz, 1H), 7.73 (dt, J=7.6, 1.0Hz, 1H), 7.62-7.54 (m, 2H ),7.39(dd,J=8.2,1.5Hz,1H),7.25(s,2H),7.16(ddd,J=8.1,7.1,1.2Hz,1H),4.78(ddd,J=11. 6,2.0,0.8Hz,1H),3.85(s,3H),3.74-3.66(m,2H),3.61(s,3H),3.57-3.48(m,5H),3.41(s,3H) ,3.26(dd,J=9.6,8.7Hz,1H),2.53(ddd,J=12.8,5.0,2.0Hz,1H),1.97(dt,J=12.9,11.4Hz,1H).

[0133] 13 C NMR (126MHz, CDCl3) δ148.53,142.11,139.96,136.60,127.46,125.18,122.60,122.19,120.56, 120.17,119.73,117.69,112.80,82.86,80.29,72.19,71.76,60.60,59.41,56.98,55.79,36.39.

[0134] HRMS (ESI-TOF) Calcd for C 23 H 28 N2O5[M+Na] +:435.1896,found:435.1899.

[0135] Example 17

[0136]

[0137] Under inert gas, indole substrate 1a (0.11 mmol), glycal 2e (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask. After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3q.

[0138] Characterization results of compound 3q: 1 H NMR (500MHz, CDCl3) δ8.10 (dd, J=4.8, 1.4Hz, 1H), 7.70 (d, J=7.9Hz, 1H), 7.59- 7.47(m,2H),7.33-7.12(m,18H),7.07(t,J=7.5Hz,1H),4.91(d,J=10.8Hz,1H), 4.76-4.66(m,2H),4.65-4.55(m,3H),4.50(d,J=12.2Hz,1H),3.86-3.71(m,6H) ,3.68-3.56(m,2H),2.51(ddd,J=12.8,5.0,2.0Hz,1H),2.06(q,J=11.9Hz,1H).

[0139] 13 C NMR (126MHz, CDCl3) δ148.53,142.14,139.98,138.67,138.63,136.66,128.45,128.39,128.29,128.07,127.73,127.71,127.63,127.42, 127.39,125.04,122.67,122.20,120.60,120.20,120.06,117.83,11 2.84,81.32,79.54,75.13,73.44,71.93,71.51,69.82,55.82,37.19.

[0140] HRMS (ESI-TOF) Calcd for C 41 H 40 N2O5[M+Na] +:663.2835,found:663.2843.

[0141] Example 18

[0142]

[0143] Under inert gas, indole substrate 1a (0.11 mmol), glycal 2f (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask. After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3r.

[0144] Characterization results of compound 3r: 1 H NMR (500MHz, CDCl3) δ8.17 (dd, J=4.7, 1.5Hz, 1H), 7.76 (d, J=7.8Hz, 1H), 7.64 -7.50(m,2H),7.39(dd,J=8.3,1.5Hz,1H),7.32-7.12(m,10H),6.88-6.82(m,5 H),4.87(d,J=10.4Hz,1H),4.78(dd,J=11.6,1.9Hz,1H),4.70-4.47(m,5H),3 .89-3.59(m,17H),2.53(ddd,J=13.0,5.1,2.0Hz,1H),2.10(q,J=11.9Hz,1H).

[0145] 13 C NMR (126MHz, CDCl3) δ159.20,159.18,159.04,148.53,142.14,139.97,136. 64,130.88,130.80,130.74,129.70,129.39,129.32,127.43,125.05,122.63 ,122.18,120.56,120.19,120.05,117.85,113.86,113.77,113.70,112.81,81.04,79.56,74.72,73.02,71.88,71.24,69.42,55.81,55.30,55.25,37.24.

[0146] HRMS (ESI-TOF) Calcd for C 44 H 46N2O8[M+Na] + :753.3152,found:753.3169.

[0147] Example 19

[0148]

[0149] Under inert gas, indole substrate 1a (0.11 mmol), 2 g (0.1 mmol) of glycal, cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL) were added to a reaction flask. After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. The reaction mixture was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3s.

[0150] Characterization results of compound 3s: 1 H NMR (500MHz, CDCl3) δ8.05 (dd, J=4.7, 1.5Hz, 1H), 7.66-7.60 (m, 1H), 7.53-7.44 (m, 2H ),7.29-7.17(m,11H),7.12-7.06(m,3H),4.92(d,J=10.8Hz,1H),4.70-4.61(m,3H),4 .57(d,J=11.5Hz,1H),3.77-3.67(m,4H),3.55-3.48(m,1H),3.19(t,J=9.0Hz,1H),2. 47(ddd,J=12.9,5.0,2.0Hz,1H),2.02(dt,J=12.9,11.5Hz,1H),1.30(d,J=6.2Hz,3H).

[0151] 13 C NMR (126MHz, CDCl3) δ148.55,142.11,139.99,138.76,138.68,136.72,128.49,128.46,128.15,127.79,127.74,127.67,127. 39,125.13,122.72,122.27,120.65,120.24,119.77,117.83,112.95,84.56,81.14,75.43,71.51,71.48,55.83,37.34,18.83.

[0152] HRMS (ESI-TOF) Calcd for C 34 H34 N2O4[M+Na] + :557.2416,found:557.2416.

[0153] Example 20

[0154]

[0155] Under inert gas, a reaction flask was charged with indole substrate 1n (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL). After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. After completion of the reaction, the reaction solution was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3t.

[0156] Characterization results of compound 3t: 1 H NMR (500MHz, CDCl3) δ8.43(dd,J=4.7,1.8Hz,1H),7.84(d,J=7.8Hz,1H),7.71(dd,J=7.7,1. 8Hz,1H),7.46-7.23(m,17H),7.20-7.13(m,2H),7.10(ddd,J=8.0,6.3,1.7Hz,1H),5.02(d, J=11.6Hz,1H),4.81(dd,J=11.6,2.2Hz,1H),4.74-4.61(m,3H),4.58-4.41(m,2H),4.07-3. 93(m,1H),3.85-3.76(m,2H),3.75-3.65(m,2H),2.62(q,J=12.0Hz,1H),2.34-2.12(m,4H).

[0157] 13C NMR (126MHz, CDCl3) δ150.92,147.02,140.58,139.36,138.63,138.22,1 36.77,128.89,128.53,128.48,128.22,128.07,128.03,128.00,127.75, 127.63,127.37,124.79,124.75,122.75,122.69,120.71,120.39,118.21 ,111.24,78.87,74.30,73.62,72.76,72.44,70.15,69.77,32.64,18.10.

[0158] HRMS (ESI-TOF) Calcd for C 41 H 40 N2O4[M+Na] + :647.2886,found:647.2900.

[0159] Example 21

[0160]

[0161] Under inert gas, a reaction flask was added with indole substrate 1o (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv), and 1,2-dichloroethane (DCE) (1 mL). After stirring to dissolve, the reaction mixture was placed in a heating block at 40°C for 24 hours. After completion of the reaction, the reaction solution was filtered and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: a 5:1 v / v mixture of petroleum ether and ethyl acetate) to afford compound 3u.

[0162] Characterization results of compound 3u: 11H NMR (500 MHz, CDCl3) δ 8.49 (dd, J = 5.0, 1.9 Hz, 1H), 8.11 (dd, J = 8.4, 0.9 Hz, 1H), 7.74 (ddd, J = 15.8, 7.9, 1.5 Hz, 2H), 7.66 (s, 1H), 7.40 (d, J = 8.2 Hz, 1H), 7.38 - 7.30 (m, 6H), 7.26 (h, J = 2.4, 1.9 Hz, 6H), 7.24 - 7.19 (m, 4H), 7.12 - 7.07 (m, 2H), 4.98 (d, J = 11.6 Hz, 1H), 4.76 (dd, J = 11.8, 2.3 Hz, 1H), 4.69 - 4.57 (m, 3H), 4.49 - 4.39 (m, 2H), 3.98 (t, J = 1.7 Hz, 1H), 3.79 - 3.72 (m, 2H), 3.69 - 3.62 (m, 2H), 2.58 (q, J = 12.0 Hz, 1H), 2.24 - 2.17 (m, 1H).

[0163] 13 13C NMR (126 MHz, CDCl3) δ 151.42, 147.90, 138.22, 137.49, 137.33, 137.11, 134.62, 127.69, 127.42, 127.36, 127.12, 126.98, 126.90, 126.65, 126.55, 126.30, 122.35, 122.15, 120.12, 119.43, 118.92, 118.54, 113.49, 111.98, 77.73, 73.22, 72.51, 71.64, 71.06, 69.07, 68.61, 31.46.

[0164] HRMS (ESI - TOF) Calcd for C 40 H 38 N2O4 [M + Na] + : 633.2729, found: 633.2744.

[0165] Example 22

[0166]

[0167] Under inert gas protection, indole substrate 1a (0.11 mmol), glycal 2a (0.1 mmol), cobalt bromide (10 mol%), NaBArF4 (10 mol%), manganese powder (3.0 equiv) and 1,2-dichloroethane (DCE) (1 mL) were added to the reaction flask. After stirring and dissolving, the reaction was placed in a heating block at 40°C for 24 h. After the reaction, the reaction solution was filtered and distilled under reduced pressure. The crude product was separated and purified on a silica gel plate (the eluent was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1) to obtain compound 3v.

[0168] Characterization results of compound 3v: 1 H NMR (500MHz, CDCl3) δ8.20 (dd, J=4.7, 1.4Hz, 1H), 7.87 (d, J=7.9Hz, 1H), 7.55 (d, J=8.3 Hz,1H),7.42-7.21(m,20H),5.57(q,J=2.8Hz,1H),4.93(d,J=11.7Hz,1H),4.71-4.59(m ,3H),4.41(q,J=11.8Hz,2H),4.04-3.96(m,1H),3.92-3.88(m,1H),3.81(s,3H),3.74( q,J=9.0,7.6Hz,3H),2.62(ddd,J=13.1,11.0,5.6Hz,1H),2.33(dt,J=13.4,3.5Hz,1H).

[0169] 13 C NMR (125MHz, CDCl3) δ148.62,142.04,140.02,139.04,138.67,138.32,136.68,128.35,128.27,128.22,128.14,127.95,127.76,127.47, 127.45,125.65,122.76,122.32,120.83,120.71,120.18,116.36,112.37,74.96,73.66,73.26,70.47,55.80,29.72.HRMS(ESI-TOF)Calcd for C41H40N2O5[M+Na]+:663.2835,found:663.2839.

[0170] The present invention is not limited to the above-mentioned specific implementation methods. Various changes made by ordinary technicians in this field based on the above-mentioned concept without creative work are all within the scope of protection of the present invention.

Claims

1. A method for preparing 3-indole-deoxycarbonyl glycoside, characterized in that: The following steps are involved: Under a protective gas atmosphere, the glycalol donor represented by formula I, the indole substrate represented by formula II, a metal catalyst, a reducing agent, and an additive are added to an organic solvent and reacted with stirring. After the reaction, the product is purified to obtain 3-indole-deoxycarbonyl glycoside. The synthetic route is: wherein R1 is located at the C4, C5, or C6 position of the indole substrate and is selected from H, fluorine, chlorine, bromine, methyl, or methoxy; R is selected from any one of H, CH3, benzyl, benzoyl, benzenesulfonyl, p-toluenesulfonyl, tert-butyloxycarbonyl, pyridine, pyrimidine, 3-methylpyridine, 3-methoxypyridine, or 5-methylpyridine; and P represents a protecting group of the glycal donor and is selected from benzyl, methyl, p-methoxybenzyl, or propargyl. The metal catalyst is any one of scandium trifluoromethanesulfonate, copper trifluoromethanesulfonate, zinc trifluoromethanesulfonate, iron trifluoromethanesulfonate, cobalt acetate, cobalt chloride, cobalt bromide or cobalt (II) acetylacetonate; The additive is sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate; The reducing agent is zinc powder or manganese powder; The organic solvent is selected from one or a combination of two or more of N, N-dimethylformamide (DMF), tetrahydrofuran (THF), dichloromethane (DCM), toluene, 1, 2-dichloroethane (DCE), trifluorotoluene or 1, 4-dioxane; The reaction temperature is 10-60° C., and the reaction time is 12-48 hours.

2. The method for preparing 3-indole-deoxycarbonyl glycoside according to claim 1, wherein: The molar ratio of the glycal donor to the indole substrate is 1:0.5-1.5, and the glycal donor is any one of galactal, glucal or rhamnal.

3. The method for preparing 3-indole-deoxycarbonyl glycoside according to claim 1, wherein: The molar ratio of the metal catalyst to the glycalol donor is 0.01-0.2:

1.

4. The method for preparing 3-indole-deoxycarbonyl glycoside according to claim 1, wherein: The molar ratio of the additive to the metal catalyst is 0 to 3:

1.

5. The method for preparing 3-indole-deoxycarbonyl glycoside according to claim 1, wherein: The molar ratio of the reducing agent to the metal catalyst is 0 to 3:

1.

6. The method for preparing 3-indole-deoxycarbonyl glycoside according to claim 1, wherein: The amount of the organic solvent added is such that the concentration of the glycal donor is 0.01 to 0.5 mol / L.

7. The method for preparing 3-indole-deoxycarbonyl glycoside according to claim 1, wherein: The purification treatment includes filtration, reduced pressure distillation, column chromatography separation or silica gel plate (Pre-TLC) separation and purification; wherein the developing solvent used for the column chromatography separation and purification is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 1 to 10:1; the eluent used for the silica gel plate separation and purification is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 1 to 20:1.

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