Method for synthesizing heterocyclic carbon glycoside with single configuration through visible light mediated glycosylation / cyclization reaction

Abstract

The invention discloses a method for synthesizing heterocyclic carbon glycoside with a single configuration through visible light mediated glycosylation / cyclization reaction, and the method comprises the following step: synthesizing the heterocyclic carbon glycoside by taking 2-aryl phenyl isocyanide and sugar NHP ester as raw materials in a solvent under the irradiation condition of visible light with the wavelength of 450-455nm. According to the invention, different substituted 2-aryl phenyl isocyanide and sugar NHP ester are used to obtain a series of heterocyclic carbon glycosides with single configuration. Compared with a traditional synthesis method, the method does not need metal, a photosensitizer, high temperature and high pressure, conditions are relatively mild, and a unique method is provided for synthesis of heterocyclic carbon glycoside; the method has the advantages of wide substrate application range, simple operation steps, high product yield and wide application prospect.

Description

Technical Field

[0001] The invention relates to the field of biomedicine technology, and in particular to a method for synthesizing heterocyclic carbon glycosides of a single configuration through a visible light-mediated glycosylation / cyclization reaction. Background Art

[0002] Carbohydrate compounds are widely present in various living organisms such as animals, plants and microorganisms, and play a vital role in maintaining the normal life activities of organisms. Carbon glycosides are a very important class of derivatives of carbohydrates and are widely present in natural products. Carbon glycosides have been shown to have biological activities such as anti-tumor, anti-viral, anti-radiation, hypoglycemic, anti-inflammatory and antioxidant activities. Since carbon glycoside compounds are used in various biological applications as important natural products and are used as stable pharmacophores in the synthesis of enzyme inhibitors, the synthesis of carbon glycoside compounds has received increasing attention in recent years. Heterocyclic carbon glycosides, as an important class of carbon glycosides, are widely used in drug research and development. In the past few decades, due to the potential of heterocyclic carbon glycosides in medicinal chemistry and organic synthesis, researchers have made great efforts to develop methods for preparing heteroaromatic carbon glycosides. Although there are many methods for preparing heterocyclic carbon glycosides, the stereoselective control of glycosidic bonds still faces a huge challenge. Carbon glycosides usually have two configurations, α and β, but most of the current synthetic methods can only obtain a mixture of the two configurations, and only a few methods can obtain carbon glycosides with a single configuration. Moreover, most reactions directly construct carbon glycosides on heterocyclic rings, which require organometallic reagents (such as heteroaryl zinc or Grignard reagents) or heteroaryl halides and suitable sugar halides to be completed under metal catalysis such as nickel, iron or zinc, and the reaction conditions are harsh. As can be seen from the above, the control of efficient stereoselectivity in the synthesis of heterocyclic carbon glycosides is still a challenging task.

[0003] Therefore, it is necessary to develop a method for preparing heterocyclic carbon glycosides of a single configuration with mild reaction conditions, simple operation, a wide range of substrate applicability, and high atomic utilization. Summary of the invention

[0004] The present invention aims to provide a method for synthesizing a heterocyclic carbon glycoside of a single configuration by a visible light-mediated glycosylation / cyclization reaction, wherein the method synthesizes a heterocyclic carbon glycoside by a visible light-mediated glycosylation / cyclization reaction. The reaction conditions are mild, the operation is simple, the substrate has a wide range of application, and the atomic utilization rate is high, and the method has broad application prospects.

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

[0006] The present invention provides a method for synthesizing a heterocyclic carbon glycoside of a single configuration by a visible light-mediated glycosylation / cyclization reaction, the method comprising: using 2-arylphenyl isocyanide and sugar NHP ester as raw materials, under the conditions of solvent and irradiation of visible light with a wavelength of 450-455nm, synthesizing the heterocyclic carbon glycoside, the chemical reaction formula of which is:

[0007]

[0008] in:

[0009] R1 is selected from hydrogen, methoxy, methyl, tert-butyl or cyano;

[0010] R2 is selected from hydrogen, halogen, methoxy, methyl, tert-butyl, cyano or phenyl;

[0011] n is 0 or 1; OR is an oxygen-containing alkyl group or a benzyl group.

[0012] Furthermore, the sugar NHP ester 2 is selected from one of the following structures:

[0013]

[0014] Further, the method comprises:

[0015] 2-arylphenyl isocyanide, sugar NHP ester and solvent are mixed, and reacted at room temperature under argon protection and irradiation with visible light of 450-455 nm wavelength. After the reaction is completed, separation and purification are performed to obtain a heterocyclic carbon glycoside with a single configuration.

[0016] Furthermore, the solvent is selected from one of dimethyl sulfoxide, acetonitrile, tetrahydrofuran and toluene.

[0017] Furthermore, the molar ratio of the 2-arylphenyl isocyanate to the sugar NHP ester is 1:(1.2-2.0).

[0018] Furthermore, the reaction concentration of the 2-arylphenyl isocyanate is 0.05-0.2 mol / L.

[0019] The present invention uses nuclear magnetic resonance hydrogen spectrum ( 1 H NMR), carbon spectrum ( 13 C NMR) and high-resolution mass spectrometry confirmed the structure of the heterocyclic carbon glycosides, such as Figure 1 , Attachment Figure 2 .

[0020] One or more technical solutions in the embodiments of the present invention have at least the following technical effects or advantages:

[0021] 1. The present invention provides a method for synthesizing a heterocyclic carbon glycoside of a single configuration by a visible light-mediated glycosylation / cyclization reaction. The method is efficient and fast, and only requires one step of room temperature reaction to synthesize a heterocyclic carbon glycoside of a single configuration, with a yield of up to 75%-93%.

[0022] 2. The heterocyclic carbon glycosides with a single configuration synthesized by the method of the present invention have not been reported so far. The present invention obtains a series of heterocyclic carbon glycosides with a single configuration by using 2-arylphenyl isocyanide with different substitutions and sugar NHP esters. Compared with the traditional synthesis method, the present method does not require metal, photosensitizer, high temperature and high pressure, and the conditions are relatively mild, which provides a unique method for the synthesis of heterocyclic carbon glycosides; the substrate has a wide range of application, the operation steps are simple, the product yield is high, and it has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] 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 description of the embodiments. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0024] Figure 1 This is the H NMR spectrum of compound 3a of Example 1 of the present invention.

[0025] Figure 2 This is the carbon NMR spectrum of compound 3a of Example 1 of the present invention.

[0026] Figure 3 The present invention provides a reaction equation for a method for synthesizing a heterocyclic carbon glycoside of a single configuration by a visible light-mediated glycosylation / cyclization reaction, wherein compound 1 is 2-arylphenylisocyanate and compound 2 is a sugar NHP ester. DETAILED DESCRIPTION

[0027] The present invention will be described in detail below in conjunction with specific implementations and examples, and the advantages and various effects of the present invention will be more clearly presented. It should be understood by those skilled in the art that these specific implementations and examples are used to illustrate the present invention, rather than to limit the present invention.

[0028] Throughout the specification, unless otherwise specifically stated, the terms used herein should be understood as meanings commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art to which the present invention belongs. In the event of a conflict, the present specification takes precedence.

[0029] The nuclear magnetic resonance images of the present invention are measured by Varian INOVA-400 nuclear magnetic resonance instrument and Varian INOVA-600 nuclear magnetic resonance instrument, with tetramethylsilane (TMS) as internal standard (δ0ppm) and deuterated chloroform as solvent; the high-resolution mass spectrum is measured by Agilent 1946B mass spectrometer.

[0030] The following is a detailed description of a method for synthesizing a single-configuration heterocyclic carbon glycoside by a visible light-mediated glycosylation / cyclization reaction of the present application in combination with examples, comparative examples and experimental data.

[0031] Example 1. Synthesis of Compound 3a

[0032]

[0033] (1) Add a magnetic particle to a dry 10 ml reaction tube, then add 2-isocyano-1,1'-biphenyl 1a (17.9 mg, 0.1 mmol), sugar NHP ester 2a (44 mg, 0.12 mmol), then evacuate the air and backfill with argon (3 times). Add dimethyl sulfoxide (1.0 mL), transfer the reaction tube to a 450-455 nm wavelength visible light reactor (12 W) and irradiate it for 24 hours;

[0034] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 32.3 mg of the product as a white solid with a yield of 92% and a melting point of 100-102°C; 1 H NMR(400MHz,Chloroform-d)δ8.64(d,J=8.3Hz,1H),8.60(d,J=8.3Hz,1H),8.55(dd,J=8.1,1.5Hz,1H),8.15(dd,J=8.0,1.5Hz,1H),7.86–7.82(m,1H) ,7.74–7.69(m,2H),7.67–7.63(m,1H),6.39(d,J=5.8Hz,1H),6.01(s,1H), 5.06(s,1H),4.85(d,J=5.8Hz,1H),2.65(s,3H),1.65(s,3H),1.50(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 157.6, 142.9, 133.1, 130.7, 130.3, 128.5, 127.19, 127.16, 127.1, 124.6, 124.0, 122.3, 121.9, 112.0, 110.1, 85.9, 85.8, 81.6, 54.6, 26.8, 25.3. HRMS (ESI) m / z: calcd. 21 H 22 NO4[M+H] + 352.1543, measured value: 352.1542.

[0035] Example 2: Synthesis of Compound 3b

[0036]

[0037] (1) Add a magnetic particle to a dry 10 ml reaction tube, then add 2-isocyano-4-methyl-1,1'-biphenyl 1b (19.3 mg, 0.1 mmol), sugar NHP ester 2a (54 mg, 0.15 mmol), then evacuate the air and backfill with argon (3 times). Add toluene (1.0 mL), transfer the reaction tube to a 450-455 nm wavelength visible light reactor (12 W) and irradiate it for 24 hours;

[0038] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 31 mg of the product as a white solid with a yield of 85% and a melting point of 90-92°C; 1 H NMR (400MHz, Chloroform-d) δ8.58(t,J=8.0Hz,2H),8.42(d,J=8.3Hz,1H),7.96(s,1H),7.81(t,J=7.8Hz,1H),7.67(t,J=7.8Hz,1H),7.48( d,J=8.9Hz,1H),6.38(d,J=5.9Hz,1H),6.00(s,1H),5.05(s,1H),4.85(d,J=5.8Hz,1H),2.63(s,3H),2.58(s,3H),1.64(s,3H),1.49(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 157.6, 143.0, 138.7, 133.1, 130.2, 128.9, 127.2, 126.7, 124.4, 122.1, 121.69, 121.65, 111.0, 110.1, 85.8, 81.7, 54.6, 26.8, 25.2, 21.5. HRMS (ESI) m / z: Calculated value C 22 H 24 NO4[M+H] + 366.1700, measured value: 366.1698.

[0039] Example 3: Synthesis of Compound 3c

[0040]

[0041] (1) A magnetic particle was added to a dry 10 ml reaction tube, followed by 2-isocyano-4-methoxy-1,1'-biphenyl 1c (20.9 mg, 0.1 mmol) and sugar NHP ester 2a (73 mg, 0.2 mmol), and then the air was evacuated and backfilled with argon (3 times). Dimethyl sulfoxide (2.0 mL) was added, and the reaction tube was transferred to a 450-455 nm wavelength visible light reactor (12 W) and irradiated therein for 24 hours;

[0042] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 35.5 mg of the product as a white solid with a yield of 93% and a melting point of 108-110°C; 1 H NMR(400MHz,Chloroform-d)δ8.56(d,J=8.3Hz,1H),8.53(d,J=8.3Hz,1H),8. 42(d,J=9.0Hz,1H),7.82–7.78(m,1H),7.66–7.62(m,1H),7.58(d,J=2.7Hz,1 H),7.29(dd,J=9.0,2.7Hz,1H),6.37(d,J=5.8Hz,1H),6.00(s,1H),5.06(s,1 H),4.86(d,J=5.9Hz,1H),4.00(s,3H),2.65(s,3H),1.64(s,3H),1.49(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 159.0, 157.0, 143.4, 132.3, 129.3, 126.2, 125.0, 122.7, 122.0, 120.7, 117.2, 117.0, 111.0, 109.4, 109.0, 84.8, 84.7, 80.6, 54.5, 53.6, 25.7, 24.2. HRMS (ESI) m / z: calculated value [M+H] + C 22 H 24 NO5 382.1649, measured value: 382.1647.

[0043] Example 4: Synthesis of Compound 3d

[0044]

[0045] (1) Add a magnetic particle to a dry 10 ml reaction tube, then add 2-isocyano-4-tert-butyl-1,1'-biphenyl 1d (23.5 mg, 0.1 mmol), sugar NHP ester 2a (44 mg, 0.12 mmol), then evacuate the air and backfill with argon (3 times). Add dimethyl sulfoxide (0.5 mL), transfer the reaction tube to a 450-455 nm wavelength visible light reactor (12 W) and irradiate it for 24 hours;

[0046] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 33.8 mg of the product as a white solid with a yield of 83% and a melting point of 107-109°C; 1 H NMR(400MHz,Chloroform-d)δ8.61–8.58(m,2H),8.47(d,J=8.6Hz,1H),8.12(d,J=2.1Hz,1H),7.84–7.79(m,1H),7.73(dd,J=8.7,2.1Hz,1H), 7.70–7.66(m,1H),6.43(d,J=5.8Hz,1H),6.00(s,1H),5.07(s,1H),4.8 6(d,J=5.8Hz,1H),2.66(s,3H),1.64(s,3H),1.50(s,3H),1.47(s,9H). 13 C NMR (100 MHz, Chloroform-d) δ 156.4, 150.7, 141.8, 132.0, 129.2, 126.2, 125.7, 125.5, 124.4, 123.4, 121.1, 120.6, 120.5, 111.0, 109.0, 84.9, 84.7, 80.6, 53.6, 33.9, 30.3, 25.7, 24.2. HRMS (ESI) m / z: calcd. 25 H 30 NO4[M+H] + 408.2169, measured value: 408.2170.

[0047] Example 5: Synthesis of Compound 3e

[0048]

[0049] (1) A magnetic particle was added to a dry 10 ml reaction tube, followed by 3-cyano-6-isocyano-1,1'-biphenyl 1e (20.4 mg, 0.1 mmol) and sugar NHP ester 2a (44 mg, 0.12 mmol), and then the air was evacuated and backfilled with argon (3 times). Tetrahydrofuran (1.0 mL) was added, and the reaction tube was transferred to a 450-455 nm wavelength visible light reactor (12 W) and irradiated therein for 24 hours;

[0050] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 28.2 mg of the product as a white solid with a yield of 75% and a melting point of 130-132°C; 1 H NMR (400MHz, Chloroform-d) δ8.87(d,J=1.8Hz,1H),8.64(d,J=8.3Hz,1H),8.59(d,J=8.3Hz,1H),8.20(d,J=8.4Hz,1H),7.95–7.91(m,1H),7.88(dd, J=8.4,1.7Hz,1H),7.83–7.79(m,1H),6.31(d,J=5.9Hz,1H),5.97(s,1H), 5.05(s,1H),4.81(d,J=5.8Hz,1H),2.63(s,3H),1.63(s,3H),1.48(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 161.1, 144.5, 131.9, 131.8, 131.4, 130.2, 128.5, 127.69, 127.65, 124.9, 124.2, 122.2, 119.1, 112.2, 110.5, 110.1, 85.7, 85.6, 81.4, 54.7, 26.7, 25.2. HRMS (ESI) m / z: calcd. 22 H 21 N2O4[M+H] + 377.1496, measured value: 377.1498.

[0051] Example 6: Synthesis of Compound 3f

[0052]

[0053] (1) A magnetic particle was added to a dry 10 ml reaction tube, followed by 2-isocyano-4'-methyl-1,1'-biphenyl 1f (19.3 mg, 0.1 mmol) and sugar NHP ester 2a (44 mg, 0.12 mmol), and then the air was evacuated and backfilled with argon (3 times). Dimethyl sulfoxide (1.0 mL) was added, and the reaction tube was transferred to a 450-455 nm wavelength visible light reactor (12 W) and irradiated therein for 24 hours;

[0054] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 32.5 mg of the product as a white solid with a yield of 89% and a melting point of 69-71°C; 1 H NMR(400MHz,Chloroform-d)δ8.53–8.49(m,2H),8.37(s,1H),8.12(dd,J=7.9,1.6Hz,1H),7.70–7.61(m,3H),6.38(d ,J=5.8Hz,1H),5.99(s,1H),5.06(s,1H),4.86(d,J=5.8Hz,1H),2.64(s,3H),2.62(s,3H),1.65(s,3H),1.50(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 157.2, 142.5, 137.1, 132.1, 130.9, 130.6, 128.0, 127.0, 126.6, 124.8, 124.1, 122.1, 121.7, 111.9, 110.1, 85.79, 85.77, 81.6, 54.6, 26.8, 25.2, 21.9. HRMS (ESI) m / z: calcd. 22 H 24 NO4[M+H] + 366.1700, Measured value: 366.1700.

[0055] Example 7: Synthesis of Compound 3g

[0056]

[0057] (1) Add a magnetic particle to a dry 10 ml reaction tube, then add 2-isocyano-4'-methoxy-1,1'-biphenyl 1g (20.9 mg, 0.1 mmol), sugar NHP ester 2a (44 mg, 0.12 mmol), then evacuate the air and backfill with argon (3 times). Add dimethyl sulfoxide (1.0 mL), transfer the reaction tube to a 450-455 nm wavelength visible light reactor (12 W) and irradiate it for 24 hours;

[0058] (2) After the reaction was completed, silica gel column chromatography was used to separate and purify the product to obtain 34.7 mg of a white solid with a yield of 91% and a melting point of 92-94°C; 1 H NMR(400MHz,Chloroform-d)δ8.52(d,J=9.1Hz,1H),8.44(dd,J=7.4,2.0Hz,1H),8.11(dd,J=7.7,1.8Hz,1H),7.93(d,J=2.6Hz,1H),7.66–7.59(m,2H), 7.45(dd,J=9.1,2.6Hz,1H),6.36(d,J=5.8Hz,1H),5.94(s,1H),5.07(s,1H) ,4.85(d,J=5.8Hz,1H),4.01(s,3H),2.71(s,3H),1.65(s,3H),1.50(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 157.4, 155.6, 141.0, 129.6, 126.44, 126.38, 126.1, 124.9, 123.1, 122.8, 120.3, 120.2, 110.9, 109.0, 105.8, 84.9, 84.6, 80.7, 54.6, 53.6, 25.7, 24.0. HRMS (ESI) m / z: calcd. 22 H 24 NO5[M+H] + 382.1649, measured value: 382.1651.

[0059] Example 8: Synthesis of Compound 3h

[0060]

[0061] (1) A magnetic particle was added to a dry 10 ml reaction tube, followed by 4'-tert-butyl-2-isocyano-1,1'-biphenyl 1h (23.5 mg, 0.1 mmol), sugar NHP ester 2a (44 mg, 0.12 mmol), and then the air was evacuated and backfilled with argon (3 times). Dimethyl sulfoxide (0.5 mL) was added, and the reaction tube was transferred to a 450-455 nm wavelength visible light reactor (12 W) and irradiated therein for 24 hours;

[0062] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 32.6 mg of the product as a white solid with a yield of 80% and a melting point of 81-83°C; 1H NMR(400MHz,Chloroform-d)δ8.60(d,J=2.0Hz,1H),8.57(d,J=8.8Hz,1H),8.5 2(dd,J=8.0,1.6Hz,1H),8.14(d,J=7.9Hz,1H),7.92(dd,J=8.7,2.0Hz,1H),7.7 0–7.66(m,1H),7.65–7.61(m,1H),6.34(d,J=5.8Hz,1H),6.02(s,1H),5.07(s, 1H), 4.83 (d, J = 5.8Hz, 1H), 2.70 (s, 3H), 1.66 (s, 3H), 1.49 (s, 3H), 1.49 (s, 9H). 13 C NMR (150 MHz, Chloroform-d) δ 157.7, 150.2, 142.6, 130.8, 130.5, 128.4, 128.0, 127.0, 124.5, 124.0, 123.1, 121.9, 121.7, 111.9, 110.0, 85.9, 85.7, 81.9, 54.6, 35.2, 31.4, 26.7, 25.1. HRMS (ESI) m / z: calcd. 25 H 30 NO4[M+H] + 408.2169, measured value: 408.2170.

[0063] Example 9: Synthesis of Compound 3i

[0064]

[0065] (1) Add a magnetic particle to a dry 10 ml reaction tube, then add 4'-chloro-2-isocyano-1,1'-biphenyl 1i (21.4 mg, 0.1 mmol), sugar NHP ester 2a (44 mg, 0.12 mmol), then evacuate the air and backfill with argon (3 times). Add acetonitrile (1.0 mL), transfer the reaction tube to a 450-455 nm wavelength visible light reactor (12 W) and irradiate it for 24 hours;

[0066] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 30.9 mg of the product as a white solid with a yield of 80% and a melting point of 113-115°C; 1H NMR(400MHz,Chloroform-d)δ8.61(d,J=2.2Hz,1H),8.55(d,J=8.8Hz,1H),8.48( dd,J=8.1,1.5Hz,1H),8.14(dd,J=8.1,1.5Hz,1H),7.78(dd,J=8.9,2.2Hz,1H),7 .74–7.70(m,1H),7.66(td,J=7.6,7.0,1.4Hz,1H),6.39(d,J=5.8Hz,1H),5.90(s ,1H),5.06(s,1H),4.83(d,J=5.8Hz,1H),2.65(s,3H),1.64(s,3H),1.49(s,3H). 13 CNMR (100 MHz, Chloroform-d) δ 155.6, 141.7, 132.1, 130.4, 129.9, 129.8, 127.8, 126.5, 125.6, 124.5, 123.0, 122.4, 120.7, 111.1, 109.1, 84.6, 80.4, 53.7, 25.7, 24.2. HRMS (ESI) m / z: calculated value C 21 H 21 ClNO4[M+H] + 386.1154, measured value: 386.11153.

[0067] Example 10: Synthesis of Compound 3j

[0068]

[0069] (1) A magnetic particle was added to a dry 10 ml reaction tube, followed by 2'-isocyano-4-cyano-1,1'-biphenyl 1j (20.4 mg, 0.1 mmol) and sugar NHP ester 2a (44 mg, 0.12 mmol), and then the air was evacuated and backfilled with argon (3 times). Dimethyl sulfoxide (1.0 mL) was added, and the reaction tube was transferred to a 450-455 nm wavelength visible light reactor (12 W) and irradiated therein for 24 hours;

[0070] (2) After the reaction was completed, silica gel column chromatography was used to separate and purify the product to obtain 30.5 mg of a white solid with a yield of 81% and a melting point of 139-141°C; 1H NMR(400MHz,Chloroform-d)δ8.99(d,J=1.8Hz,1H),8.68(d,J=8.6Hz,1H),8.51(dd,J=8.3,1.4Hz,1H),8.17(dd,J=8.1,1.4Hz,1H),7.99(dd,J=8.6,1.7Hz ,1H),7.83–7.79(m,1H),7.74–7.69(m,1H),6.39(d,J=5.8Hz,1H),5.90(s,1H ),5.06(s,1H),4.80(d,J=5.8Hz,1H),2.61(s,3H),1.64(s,3H),1.49(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 157.0, 143.7, 135.6, 132.9, 131.6, 131.0, 130.4, 128.0, 124.0, 123.6, 122.7, 122.4, 118.6, 112.3, 110.7, 110.2, 85.6, 85.5, 81.2, 54.9, 26.8, 25.3. HRMS (ESI) m / z: calcd. 22 H 21 N2O4[M+H] + 377.1496, measured value: 377.1497.

[0071] Example 11: Synthesis of Compound 3k

[0072]

[0073] (1) A magnetic particle was added to a dry 10 ml reaction tube, followed by the addition of 2-isocyano-1,1':4',1" terphenyl 1k (25.5 mg, 0.1 mmol) and sugar NHP ester 2a (44 mg, 0.12 mmol), and then the air was evacuated and backfilled with argon (3 times). Dimethyl sulfoxide (1.0 mL) was added, and the reaction tube was transferred to a 450-455 nm wavelength visible light reactor (12 W) and irradiated therein for 24 h;

[0074] (2) After the reaction was completed, silica gel column chromatography was used to separate and purify the product to obtain 34.6 mg of a white solid with a yield of 81% and a melting point of 89-91°C; 1H NMR(400MHz,Chloroform-d)δ8.84(d,J=1.9Hz,1H),8.69(d,J=8.6Hz,1H),8.56(dd,J=8.1, 1.6Hz,1H),8.16(dd,J=8.0,1.5Hz,1H),8.10(dd,J=8.6,1.9Hz,1H),7.82–7.79(m,2H),7.74 –7.70(m,1H),7.69–7.64(m,1H),7.54(t,J=7.7Hz,2H),7.46–7.42(m,1H),6.43(d,J=5.8Hz, 1H), 6.06 (s, 1H), 5.08 (s, 1H), 4.87 (d, J = 5.8Hz, 1H), 2.68 (s, 3H), 1.66 (s, 3H), 1.51 (s, 3H). 13 C NMR (100 MHz, Chloroform-d) δ 156.7, 141.8, 139.3, 138.8, 131.1, 129.7, 128.4, 128.0, 127.5, 126.8, 126.5, 126.2, 124.2, 124.0, 122.9, 121.8, 120.8, 110.9, 109.1, 84.73, 84.69, 80.6, 53.6, 25.7, 24.1. HRMS (ESI) m / z: calcd. 27 H 26 NO4[M+H] + 428.1856, measured value: 428.1858.

[0075] Example 12: Synthesis of Compound 31

[0076]

[0077] (1) Add a magnetic particle to a dry 10 ml reaction tube, then add 2-isocyano-1,1'-biphenyl 1a (17.9 mg, 0.1 mmol), sugar NHP ester 2b (42 mg, 0.12 mmol), then evacuate the air and backfill with argon (3 times). Add dimethyl sulfoxide (1.0 mL), transfer the reaction tube to a 450-455 nm wavelength visible light reactor (12 W) and irradiate it for 24 hours;

[0078] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 50.9 mg of the product as a white solid with a yield of 77% and a melting point of 165-167°C; 1H NMR(400MHz,Chloroform-d)δ7.36–7.25(m,10H),7.14(t,J=7.7Hz,2H),6.73–6.68(m,3H),5. 00(d,J=4.0Hz,1H),4.90(s,1H),4.81(dd,J=8.1,3.9Hz,1H),4.67(d,J=11.9Hz,1H),4.57(d,J =11.8Hz,1H),4.42–4.34(m,3H),3.88(d,J=4.5Hz,1H),3.84–3.81(m,1H),3.49–3.40(m,2H),3 .28(s,3H),1.91–1.62(m,5H),1.33–1.26(m,1H),1.24–1.16(m,1H),0.94(s,3H),0.83(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 169.9, 146.8, 137.8, 137.6, 129.1, 128.42, 128.39, 128.1, 127.82, 127.79, 127.7, 118.1, 113.7, 106.4, 81.6, 79.1, 77.0, 72.4, 72.3, 65.3, 58.4, 55.7, 53.0, 48.6, 47.6, 44.2, 37.3, 32.6, 26.4, 20.6, 19.9. HRMS (ESI) m / z: calcd. 37 H 45 N2O7S[M+H] + 661.2942, measured value: 661.2938.

[0079] Example 13: Synthesis of Compound 3m

[0080]

[0081] (1) Add a magnetic particle to a dry 10 ml reaction tube, then add 2-isocyano-1,1'-biphenyl 1a (17.9 mg, 0.1 mmol), sugar NHP ester 2c (60 mg, 0.12 mmol), then evacuate the air and backfill with argon (3 times). Add dimethyl sulfoxide (1.0 mL), transfer the reaction tube to a 450-455 nm wavelength visible light reactor (12 W) and irradiate it for 24 hours;

[0082] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 41.8 mg of the product as a white solid with a yield of 85% and a melting point of 103-105°C; 1H NMR(400MHz,Chloroform-d)δ8.64(d,J=8.3Hz,1H),8.56(d,J=7.3Hz,2H),8.14(d,J=8.0 Hz,1H),7.86–7.82(m,1H),7.74–7.65(m,3H),7.47(d,J=7.1Hz,2H),7.40–7.33(m,6H),7 .28–7.23(m,2H),5.97(d,J=6.3Hz,1H),5.51(dd,J=6.3,4.7Hz,1H),5.12(s,1H),4.80(s ,2H),4.77(d,J=12.1Hz,1H),4.71(d,J=11.9Hz,1H),4.17(d,J=4.7Hz,1H),3.10(s,3H). 13 C NMR(100MHz,Chloroform-d)δ156.0,142.1,137.3,137.0,132.1,129.6,129. 3,127.41,127.37,127.2,127.1,126.9,126.8,126.5,126.3,126.11,126.08,

[0084] 124.6,123.3,121.1,120.9,106.0,80.3,79.9,78.2,71.8,71.7,54.0. HRMS (ESI) m / z: Calculated value C 32 H 30 NO4[M+H] + 492.2169, measured value: 492.2167.

[0085] Example 14: Synthesis of Compound 3n

[0086]

[0087] (1) Add a magnetic particle to a dry 10 ml reaction tube, then add 2-isocyano-1,1'-biphenyl 1a (17.9 mg, 0.1 mmol), sugar NHP ester 2d (64 mg, 0.12 mmol), then evacuate the air and backfill with argon (3 times). Add dimethyl sulfoxide (1.0 mL), transfer the reaction tube to a 450-455 nm wavelength visible light reactor (12 W) and irradiate it for 24 hours;

[0088] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 41.5 mg of the product as a white solid with a yield of 80% and a melting point of 117-119°C; 1H NMR(400MHz,Chloroform-d)δ8.68(d,J=8.3Hz,1H),8.62(d,J=8.2Hz,1H),8.57(dd,J=8.0,1 .6Hz,1H),8.27–8.24(m,1H),8.06–8.04(m,2H),8.02–8.00(m,2H),7.90–7.86(m,1H),7.77– 7.66(m,3H),7.58–7.49(m,2H),7.40(t,J=7.7Hz,2H),7.35(t,J=7.7Hz,2H),7.16(t,J=5.0H z,1H),6.25(d,J=5.0Hz,1H),6.03(dd,J=5.1,1.8Hz,1H),5.39(d,J=1.8Hz,1H),3.15(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 164.5, 164.4, 154.5, 132.4, 132.3, 132.1, 130.0, 129.5, 128.8, 128.7, 128.6, 128.5, 127.6, 127.4, 127.3, 126.4, 126.3, 125.7, 124.0, 123.2, 121.4, 120.8, 106.4, 81.0, 75.4, 72.9, 54.3. HRMS (ESI) m / z: calcd. 32 H 26 NO6[M+H] + 520.1755, measured value: 520.1751.

[0089] Example 15: Synthesis of Compound 3o

[0090]

[0091] (1) Add a magnetic particle to a dry 10 ml reaction tube, then add 2-isocyano-1,1'-biphenyl 1a (17.9 mg, 0.1 mmol), sugar NHP ester 2e (53 mg, 0.12 mmol), then evacuate the air and backfill with argon (3 times). Add dimethyl sulfoxide (1.0 mL), transfer the reaction tube to a 450-455 nm wavelength visible light reactor (12 W) and irradiate it for 24 hours;

[0092] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 33.3 mg of the product as a white solid with a yield of 78% and a melting point of 91-93°C; 1H NMR(400MHz,Chloroform-d)δ8.64(d,J=8.3Hz,1H),8.57(d,J=8.0Hz,1H),8.50(d,J=8 .3Hz,1H),8.17(dd,J=8.0,1.5Hz,1H),7.83(t,J=7.7Hz,1H),7.75–7.65(m,3H),7.37–7 .25(m,5H),6.16(d,J=4.2Hz,1H),5.82(d,J=4.6Hz,1H),5.53(d,J=4.5Hz,1H),4.95(d, J=4.5Hz,1H),4.82(d,J=11.5Hz,1H),4.72(d,J=11.5Hz,1H),1.37(s,3H),1.30(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 154.6, 141.9, 136.6, 129.6, 129.4, 127.5, 127.4, 126.9, 126.8, 126.3, 126.2, 125.9, 124.1, 123.3, 121.2, 120.9, 112.7, 104.8, 85.1, 83.4, 83.2, 71.4, 26.1, 25.9. HRMS (ESI) m / z: calcd. 27 H 26 NO4[M+H] + 428.1856, measured value: 428.1855.

[0093] Example 16: Synthesis of Compound 3p

[0094]

[0095] (1) Add a magnetic particle to a dry 10 ml reaction tube, then add 2-isocyano-1,1'-biphenyl 1a (17.9 mg, 0.1 mmol), sugar NHP ester 2f (47 mg, 0.12 mmol), then evacuate the air and backfill with argon (3 times). Add dimethyl sulfoxide (1.0 mL), transfer the reaction tube to a 450-455 nm wavelength visible light reactor (12 W) and irradiate it for 24 hours;

[0096] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 31.8 mg of the product as a white solid with a yield of 83% and a melting point of 136-138°C; 1H NMR(600MHz,Chloroform-d)δ8.70(d,J=8.2Hz,1H),8.59(d,J=8.1Hz,1H),8.45(d,J= 8.3Hz,1H),8.28(s,1H),7.87(t,J=7.7Hz,1H),7.76–7.72(m,2H),7.69(t,J=7.3Hz,1H ),5.59(d,J=9.7Hz,1H),5.01(d,J=3.6Hz,1H),4.27(t,J=9.3Hz,1H),3.83(t,J=9.4Hz ,1H),3.71(s,3H),3.62(s,3H),3.61(s,3H),3.57(dd,J=9.9,3.6Hz,1H),3.17(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 155.3, 132.4, 129.6, 129.5, 127.6, 126.41, 126.39, 124.7, 124.6, 123.2, 121.5, 120.9, 97.8, 82.8, 81.4, 80.6, 68.5, 60.1, 59.3, 58.2, 55.3. HRMS (ESI) m / z: calculated value C 22 H 26 NO5[M+H] + 384.1805, measured value: 384.1803.

[0097] Example 17: Synthesis of Compound 3q

[0098]

[0099] (1) Add a magnetic particle to a dry 10 ml reaction tube, then add 2-isocyano-1,1'-biphenyl 1a (17.9 mg, 0.1 mmol), sugar NHP ester 2g (75 mg, 0.12 mmol), then evacuate the air and backfill with argon (3 times). Add dimethyl sulfoxide (1.0 mL), transfer the reaction tube to a 450-455 nm wavelength visible light reactor (12 W) and irradiate it for 24 hours;

[0100] (2) After the reaction was completed, the product was directly separated and purified by silica gel column chromatography to obtain 46.5 mg of the product as a white solid with a yield of 76% and a melting point of 157-159°C; 1H NMR(400MHz,Chloroform-d)δ8.68(d,J=8.3Hz,1H),8.58(dd,J=8.0,1.6Hz,1H),8.45(d,J=8.3Hz,1H),8.23(d,J=8.0Hz,1H),7. 89–7.84(m,1H),7.76–7.67(m,3H),7.45–7.41(m,4H),7.38–7.31(m,6H),6.94(t,J=7.4Hz,1H),6.85(t,J=7.5Hz,2H),6.55(d,J =7.0Hz,2H),5.73(d,J=9.7Hz,1H),5.07(d,J=10.9Hz,1H),4.94(d,J=8.4Hz,1H),4.92(d,J=9.7Hz,1H),4.81(d,J=3.6Hz,1H),4 .77(d,J=12.2Hz,1H),4.59–4.53(m,2H),4.31(t,J=9.4Hz,1H),4.20(d,J=10.7Hz,1H),3.89(dd,J=9.8,3.6Hz,1H),3.58(s,3H). 13 C NMR (100 MHz, Chloroform-d) δ 155.4, 137.9, 137.2, 136.7, 132.3, 129.50, 129.46, 127.6, 127.5, 127.4, 127.2, 127.0, 126.9, 126.8, 126.7, 126.6, 126.3, 126.1, 124.9, 124.6, 123.1, 121.4, 120.9, 98.4, 81.4, 79.9, 78.8, 74.9, 73.8, 72.6, 55.2. HRMS (ESI) m / z: calcd. 40 H 38 NO5[M+H] + 612.2744, measured value: 612.2742.

[0101] Finally, it should be noted that the terms "comprises," "includes," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements that are inherent to such process, method, article, or apparatus.

[0102] Although the preferred embodiments of the present invention have been described, those skilled in the art may make other changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0103] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A method for synthesizing a single-configuration heterocyclic carbon glycoside by a visible light-mediated glycosylation / cyclization reaction, characterized in that: The method comprises: using 2-arylphenyl isocyanide and sugar NHP ester as raw materials, under the conditions of solvent and irradiation of visible light with a wavelength of 450-455nm, synthesizing heterocyclic carbon glycoside, and the chemical reaction formula is: in: R1 is selected from hydrogen, methoxy, methyl, tert-butyl or cyano; R2 is selected from hydrogen, halogen, methoxy, methyl, tert-butyl, cyano or phenyl; n is 0 or 1; OR is an oxygen-containing alkyl group or a benzyl group, and the sugar NHP ester is selected from one of the following structures:

2. The method for synthesizing a single-configuration heterocyclic carbon glycoside by a visible light-mediated glycosylation / cyclization reaction according to claim 1, characterized in that: 2-arylphenyl isocyanide, sugar NHP ester and solvent are mixed, and reacted at room temperature for 24 hours under argon protection and irradiation with visible light of 450-455 nm wavelength. After the reaction is completed, separation and purification are performed to obtain a heterocyclic carbon glycoside with a single configuration.

3. The method for synthesizing a heterocyclic carbon glycoside of a single configuration by a visible light-mediated glycosylation / cyclization reaction according to claim 2, characterized in that: The solvent is selected from the group consisting of dimethyl sulfoxide, acetonitrile, tetrahydrofuran and toluene.

4. The method for synthesizing a heterocyclic carbon glycoside of a single configuration by a visible light-mediated glycosylation / cyclization reaction according to claim 2, characterized in that: The molar ratio of the 2-arylphenyl isocyanate to the sugar NHP ester is 1:(1.2-2.0).

5. The method for synthesizing a single-configuration heterocyclic carbon glycoside by a visible light-mediated glycosylation / cyclization reaction according to claim 2, characterized in that: The reaction concentration of the 2-arylphenyl isocyanide is 0.05-0.2 mol / L.

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