A method for synthesizing beta-d-glucosyl-5-hydroxymethyluracil

Abstract

This application discloses a method for synthesizing β-D-glucosyl-5-hydroxymethyluracil, which simply and efficiently synthesizes the following two β-D-glucosyl-5-hydroxymethyluracil compounds (base J). The synthesis conditions are mild, and the reaction exhibits high stereoselectivity and regioselectivity, making the synthetic base J environmentally friendly.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for synthesizing β-D-glucosyl-5-hydroxymethyluracil. Background Technology

[0002] β-D-glucosyl-5-hydroxymethyluracil (base J) was the first highly modified base discovered in eukaryotic DNA. Over the past three decades, this unique modified base has been found in members of the unicellular kinetoplast family, such as trypanosomes and leishmania species, as well as the associated unicellular flagellate protozoan *Euglena gracilis*, where it replaces a small portion of thymine in the genome. In contrast to its presence in unicellular protozoa, the J base was not detected in the tested animals, plants, or fungi, or in a range of other simple eukaryotes. In all the kinetoplasts analyzed, base J was predominantly located in telomere repeat regions (telomere J), ​​with a small subset present in other repetitive DNA sequences and sequences between transcription units (internal J). In the parasite *Trypanosoma brevicornu*, it also appears at the expression site of the subtelomere variant surface glycoprotein (VSG) gene, involved in the production of a VSG shell on the cell surface to evade the host immune response. The unique presence of J in the kinetoplast genome makes J base and J biosynthesis potential targets for parasite-specific chemotherapy. Studies have shown that the biosynthesis of J involves two steps: first, the de novo hydroxylation of a specific thymidine residue to 5-hydroxymethyl-2′-deoxyuridine (5-HmdU), and then the intermediate 5-HmdU is converted to β-D-glucosyl-5-hydroxymethyl-2′-deoxyuridine (dJ) by glucose transferase. Indeed, studies have identified two enzymes involved in catalyzing thymidine oxidation in trypanosomes, namely J-binding proteins 1 and 2 (JBP1 and JBP2).

[0003] Because the naturally occurring base J is rare and difficult to obtain, sample acquisition has become a bottleneck restricting further research on its biological activity. Chemical synthesis is one of the effective ways to overcome this bottleneck. However, according to literature review, there are very few reports on the chemical synthesis of base J. The Boom research group mainly uses 2-deoxyuridine as a raw material, then oxidizes the 5-position of uracil, followed by a series of protecting group operations, and then introduces glucose onto the hydroxymethyl group using Schmidt donor or bromoglycoside. The main drawbacks of this method include: firstly, the oxidation of uracil at the 5-position in 2-deoxyuridine requires 5 days and the yield is only 40%, which is low; secondly, when introducing glucose using a bromoglycoside donor, an equivalent amount of toxic mercury reagent is required, which is not environmentally friendly or operator-friendly, and the yield is only about 50%. Using Schmidt donor as a promoter can achieve a catalytic amount of TMSOTf, but the yield of the glycosylation reaction is only 47% (References: de Kort, M., Ebrahimi, E., Wijsman, ER, van der Marel, GA, van Boom, JHEur. J. Org. Chem. 1999, 2337-2344. References: Turner, JJ, Meeuwenoord, NJ, Rood, A., Borst, P., van der Marel, GA, van Boom, JHEur. J. Org. Chem. 2003, 3832-3839.). Therefore, existing chemical synthesis methods for the base J are inefficient. To better study the biological function of this unique base, this application develops a highly efficient chemical synthesis method for the base J. Summary of the Invention

[0004] To address the shortcomings of existing methods for synthesizing base J, the present invention aims to provide a method for synthesizing β-D-glucosyl-5-hydroxymethyluracil.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] A method for synthesizing β-D-glucosyl-5-hydroxymethyluracil includes the following steps:

[0007]

[0008] R1 is a hydroxyl protecting group, and R2 is an acyl protecting group.

[0009] (1) Compound 1a and Compound 2 were dissolved in an organic solvent, and Compound 3 was obtained in the presence of a desiccant and a catalyst.

[0010] (2) Compounds 3 and 4 were dissolved in an organic solvent and, in the presence of a desiccant and a catalyst, compound 5 was obtained.

[0011] (3) Compound 5, 4-ClPN and adamantane thiol were dissolved in an organic solvent and reacted completely under a protective atmosphere and under blue LED light to obtain compound 6.

[0012] (4) Compound 6 was deprotected to obtain compound 7.

[0013] Further, in steps (1) and (2), the organic solvent is preferably one or more of dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, DMF, toluene, benzene, dioxane, tetrahydrofuran, pyridine, ethyl acetate, DMSO, or diethyl ether. The catalyst is a monovalent gold complex, preferably PPh3AuNTf2 or PPh3AuOTf. The desiccant is a molecular sieve, preferably... Molecular sieves or acid-washed molecular sieves are preferred. Molecular sieve.

[0014] Further, in step (1), the molar ratio of compound 1, compound 2, and catalyst is 1:(1.5–2.5):

[0015] (0.1~0.3), based on compound 2, the amount of molecular sieve added is 1.5~2.0 g / mmol; in step (2), the molar ratio of compound 3, compound 4 and catalyst is 1:(1~2):(0.2~0.4), based on compound 3, the amount of molecular sieve added is 5~8 g / mmol; in step (3), the molar ratio of compound 5, 4-ClPN and adamantane thiol is 1:(0.01~0.03):

[0016] (0.1~0.2), the wavelength of the blue LED light is 430~500nm, and the organic solvent is at least one of ethyl acetate, tetrahydrofuran, toluene and acetonitrile.

[0017] Further, in step (1), fluoroisopropanol is added to the organic solvent, and the volume ratio of the organic solvent to hexafluoroisopropanol is (3-5):1.

[0018] Furthermore, in step (4), compound 6 first undergoes the removal of the silicon-based protecting group under the action of acetic acid and tetrabutylammonium fluoride, and then undergoes the removal of R1 and R2 protection under the action of alkali.

[0019] Preferably, the molar ratio of compound 6, acetic acid and tetrabutylammonium fluoride is 1:(5-10):(0.003-0.005), the molar ratio of the silicon-removed compound and the base is 1:(5-8), and the base is at least one of K2CO3, KHCO3, Na2CO3 and NaHCO3.

[0020] A method for synthesizing β-D-glucosyl-5-hydroxymethyluracil includes the following steps:

[0021]

[0022] R1 and R5 are hydroxyl protecting groups, and R2 is an acyl protecting group.

[0023] S1. Remove the silicon-based protecting group from compound 4 and protect it with the R5 protecting group to obtain 1c and 1c';

[0024] S2. Compound 1c or 1c' and compound 8 are dissolved in an organic solvent, and 9 and 9' are obtained under the action of a drying agent, an accelerator and a catalyst.

[0025] S3. After removing TBDPS protection from 9 or 9', it is dissolved in an organic solvent along with compound 1a, and under the action of a drying agent and a catalyst, compounds 10 and 10' are obtained.

[0026] S4. Dissolve compound 10 or 10', 4-ClPN and adamantane thiol in an organic solvent, and stir the reaction under a protective atmosphere and under blue LED light to obtain compound 11 or 11'.

[0027] S5. Remove the protecting group from compound 11 or 11' to obtain compound 7 or 7'.

[0028] Further, in steps S2 and S3, the organic solvent is preferably one or more of dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, DMF, toluene, benzene, dioxane, pyridine, glacial acetic acid, tetrahydrofuran, triethylamine, ethyl acetate, acetone, methanol, ethanol, DMSO, or diethyl ether. The catalyst is a monovalent gold complex, preferably PPh3AuNTf2 or PPh3AuOTf. The promoter is BSTFA, NIS, or TMSOT, preferably BSTFA. The drying agent is a molecular sieve, preferably... Molecular sieves or acid-washed molecular sieves are preferred. Molecular sieve.

[0029] In step S2, the molar ratio of compound 1c or 1c', compound 8, promoter, and catalyst is 1:(1-2):

[0030] (4~8):(0.02~0.2); Based on compound 8, the amount of molecular sieve added is 1~2 g / mmol; In step S3, the molar ratio of the deprotected TBDPS compound to compound 1a is 1:(1~1.5), and the molar ratio of compound 1a to catalyst is 1:

[0031] (0.02~0.2), based on the compound deprotected from TBDPS, the amount of molecular sieve added is 3~5 g / mmol; in step S4, compound 10 or 10', 4-ClPN and adamantane thiol 1:(0.01~0.03):(0.2~2), the wavelength of the blue LED lamp is 430~500nm, and the organic solvent is at least one of ethyl acetate, tetrahydrofuran, toluene and acetonitrile.

[0032] Further, in step S1, compound 4 undergoes the removal of the silicon-based protecting group under the action of acetic acid and tetrabutylammonium fluoride. The molar ratio of compound 4, acetic acid and tetrabutylammonium fluoride is 1:(5-15):(3-8).

[0033] The preparation process of compound 4 is as follows:

[0034]

[0035] G1 is a hydroxyl protecting group, G2 is an acyl protecting group, and X is Cl, Br, or I;

[0036] The specific synthesis process is as follows:

[0037] The specific synthesis process is as follows:

[0038] a. Compound S2 and 2-halogenated thiophenol were reacted under Lewis acid conditions to obtain compound S3;

[0039] b. Compound S3 and 3,3-dimethyl-1-butyne undergo a Sonogashira reaction to give compound 1b;

[0040] c. Compound 1b was reduced to obtain a triol intermediate; the triol intermediate was reacted with TIPSCl to obtain compound S4;

[0041] d. Compound S4 and DHPCOOH were subjected to esterification to obtain compound 4.

[0042] In step a, the molar ratio of compound S2, 2-halogenated thiophenol, and Lewis acid is 1:(1.5~2):(2~3), and the Lewis acid is BF3-Et2O; in step b, the Sonogashira reaction includes the following steps: dissolving compound S3, Ph3P, Pd(PPh3)2Cl2, and CuI in an organic solvent, cooling to -78℃~-40℃ in an inert gas atmosphere, adding 3,3-dimethyl-1-butyne, and heating to 5℃. After reaching 0–100°C, the reaction is continued until TLC shows complete reaction. The organic solvent is selected from one or more of N,N-dimethylformamide, diisopropanolamine, tetrahydrofuran, dichloromethane, acetone, and toluene. Preferably, the molar ratio of compound S3, 3,3-dimethyl-1-butyne, (PPh3)2PdCl2, CuI, and PPh3 is 1:(2.5–3.5):(0.08–0.12):(0.3–0.5):(0.3–0.5). In step c, the molar ratio of the triol intermediate to TIPSCl is 1:(1–1.5). In step d, compound S4 and DHPCOOH undergo esterification under the action of EDCI, DMAP, and DIPEA, and the molar ratio of compound S4, DHPCOOH, EDCI, DMAP, and DIPEA is 1:(1–1.5):3:2:5.

[0043] The preparation process of compound 1 is as follows:

[0044]

[0045] R1 is a hydroxyl protecting group, R2 is an acyl protecting group, and X is Cl, Br, or I. Compound S1 and 3,3-dimethyl-1-butyne undergo a Sonogashira reaction to give compound 1a.

[0046] The Sonogashira reaction comprises the following steps: dissolving compounds S1, Ph3P, Pd(PPh3)2Cl2, and CuI in an organic solvent; cooling to -78°C to -40°C under an inert gas atmosphere; adding 3,3-dimethyl-1-butyne; heating to 50–100°C; and reacting until TLC shows complete reaction. The organic solvent is selected from one or more of N,N-dimethylformamide, diisopropanolamine, tetrahydrofuran, dichloromethane, acetone, and toluene.

[0047] Furthermore, the molar ratio of compound S1, 3,3-dimethyl-1-butyne, (PPh3)2PdCl2, CuI and PPh3 is 1:(2.5~3.5):(0.08~0.12):(0.3~0.5):(0.3~0.5).

[0048] Preferably, R1, G1, and R5 are selected from Bz, Ac, CA, Lev, TBDPS, TBS, Ts, All, Nap, or Bn, and R2 and G2 are selected from Bz, Ac, Boc, CA, or Lev. TBDPS is tert-butyldiphenylsilyl, TBS is tert-butyldimethylsilyl, Ts is p-toluenesulfonyl, All is allyl, Nap is 2-methylnaphthyl, Bn is benzyl, Ac is acetyl, Bz is benzoyl, CA is chloroacetyl, Lev is acetylpropionyl, and Boc is tert-butyloxycarbonyl.

[0049] The β-D-glucosyl-5-hydroxymethyluracil compound obtained by the above synthetic method has the following structure:

[0050]

[0051] This invention provides a novel glycosyl donor, which is simple to operate under mild conditions and exhibits high stereoselectivity and regioselectivity, making it an environmentally friendly synthetic base J. Detailed Implementation

[0052] The technical solution of the present invention will be further described in detail below with reference to specific embodiments.

[0053] Example 1

[0054] (1) Synthesis of donor 1

[0055]

[0056] (PPh3)2PdCl2 (125 mg, 0.19 mmol), CuI (145 mg, 0.77 mmol), PPh3 (202 mg, 0.77 mmol), and S1 (1.0 g, 1.93 mmol) were added to a mixed solvent of DMF / DIPA (24 mL, v / v = 1:2). The mixture was evacuated and purged with nitrogen. 3,3-Dimethyl-1-butyne (0.7 mL, 5.7 mmol) was added at -78 °C. The mixture was sealed and stirred at 80 °C for 8 h. The reaction was then cooled to room temperature, quenched with saturated NH4Cl solution, and desalted using a short silica gel column. The solution was diluted with ethyl acetate and washed successively with water and saturated brine. After filtration, the solution was concentrated by rotary evaporation to obtain the crude product 1a. This crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain donor 1a (0.98 g, 98%), a white, foamy solid. [α] D 25 = +4.4 (c 0.5, CHCl3); 1H NMR(400MHz, CDCl3)δ8.08-7.98(m,2H),7.94-7.91(m,4H),7.82-7.80(m,2H) ,7.58-7.23(m,14H),7.05(td,J=7.6,1.1Hz,1H),6.90(td,J=7.7,1.5Hz,1H), 6.00(t,J=9.5Hz,1H),5.73-5.64(m,2H),5.29(d,J=10.0Hz,1H),4.68(dd,J=1 2.2, 2.6Hz, 1H), 4.49 (dd, J = 12.2, 6.9Hz, 1H), 4.33-4.28 (m, 1H), 1.10 (s, 9H); 13 C NMR (100MHz, CDCl3) δ166.2,165.9,165.4,165.15,136.9,133.7,133.4,133.3,132.1,130.05,130.0,129.9,129.8,129.65,129.1,128. 8,128.75,128.6,128.55,128.5,128.4,128.1,126.4,124.5,105.7,84.9,76.6,76.4,74.2,70.6,69.8,63.7,30.7,28.2; HRMS(ESI)m / z calcd for C 46 H 44 O9SN[M+NH4] + :786.2731; found:786.2732.

[0057] (2) Synthesis of donor 1b

[0058]

[0059] S2 (2.0 g, 5.12 mmol) was dissolved in dry dichloromethane (20 mL). 2-Bromothiophenol (1.1 mL, 9.2 mmol) and BF3-Et2O (1.8 mL, 12.8 mmol) were added under ice bath conditions. The mixture was heated to room temperature and stirred until the substrate reaction was complete as detected by TLC. The reaction was quenched with triethylamine, diluted with dichloromethane, washed with saturated NaHCO3, dried over anhydrous Na2SO4, filtered, and concentrated by rotary evaporation to obtain crude S3. S3 (2.40 g, 90%) was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1).

[0060] Donor 1b (0.95 g, 94%) was prepared by replacing S1 with S3 (1.0 g, 1.58 mmol) in step (1). It was a white, foamy solid. For the β configuration: [α]D 25 = +23.6 (c 0.5, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.08(d,J=7.8Hz,2H),7.99(d,J=7.8Hz,2H),7.89(d,J=7.7Hz,2H),7.61(d,J=7.7Hz,1H),7.56-7.48(m,3H),7.40 -7.36(m,5H),7.31(t,J=7.7Hz,2H),7.24-7.13(m,2H),5.94-5.88(m,3H),4.75-4.69(m,2H),4.60(dd,J=11.5,4.3Hz,1H),1.28(s,9H). 13 C NMR (100MHz, CDCl3) δ166.25,165.3,165.1,135.2,133.6,133.5,133.2,132.6,131.3,129.9,129.8,129.7,129 .1,129.0,128.5(2C),128.15,127.2,126.0,105.05,87.3,80.3,75.65,72.7,64.45,30.9,28.3.; HRMS(ESI)m / z calcd for C 38 H 38 O7SN[M+NH4] + :652.2363; found:652.2333.

[0061] (3) Synthesis of donor 4

[0062]

[0063] 1b (5.0 g, 7.9 mmol) was dissolved in CH3OH (20 mL), and a catalytic amount of CH3ONa (freshly prepared) was added. The mixture was stirred until the substrate reaction was complete as detected by TLC. After filtration, the mixture was concentrated by rotary evaporation and purified by silica gel column chromatography (CH2Cl2 / MeOH = 40:1) to obtain a triol intermediate (white solid, 2.3 g, 90%).

[0064] The above intermediate (2.3 g, 7.1 mmol) was dissolved in dry pyridine (14 mL). TIPSCl (2.75 mL, 9.23 mmol) was added under ice bath conditions (0 °C). The mixture was brought to room temperature and stirred until the substrate reaction was complete as detected by TLC. After dilution with EtOAc, the solution was washed successively with 1 M HCl and saturated brine. The solution was dried over anhydrous Na₂SO₄, filtered, concentrated by rotary evaporation, and purified by silica gel column chromatography (CH₂Cl₂ / MeOH = 50:1) to obtain S₄ (3.7 g, 92%), a pale yellow syrup. [α] D 25 = -93.3 (c 1.0, CHCl3); 1 HNMR (400MHz, CDCl3) δ7.44(dd,J=7.9,1.3Hz,1H),7.37(dd,J=7.6,1.6Hz,1H),7.20(td,J=7.7,1.6Hz,1H),7.14(td,J=7.5,1.3Hz,1H),5.57(d,J= 1.6Hz,1H),4.47(t,J=5.9Hz,1H),4.29-4.22(m,1H),4.06-3.92(m,3H),3 .09(d,J=1.9Hz,1H),1.35(s,9H),1.14-1.09(m,7H),1.09-1.02(m,21H); 13 C NMR (100MHz, CDCl3) δ136.5,132.6,130.2,128.1,126.5,125.2,105.1,88.6,83.1,76.9,74 .6,64.8,31.0,17.6(2C),17.5(2C),17.4,17.2,17.1,13.4(2C),12.9,12.8.HRMS(ESI)m / z calcd for C40H35BrO9SN[M+NH4] + :784.1210; found:784.1217.

[0065] S4 (1.1 g, 1.94 mmol) was dissolved in dry dichloromethane (4.8 mL). DHPCOOH (750 mg, 2.52 mmol), EDCI (1.11 g, 5.82 mmol), DMAP (474 ​​mg, 3.88 mmol), and DIPEA (1.68 mL, 9.7 mmol) were added at 0 °C. The mixture was brought to room temperature and stirred until the substrate reaction was complete, as detected by TLC. The resulting solution was concentrated by rotary evaporation and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to give donor 4 (1.52 g, 92%) as a white solid. [α] D 25= -30.3 (c 1.0, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.38 (dd, J=7.8, 1.3Hz, 1H), 7.34 (dd, J=7.6, 1.6Hz, 1H), 7.18 (td, J=7.7, 1.6Hz, 1H ),7.11(td,J=7.5,1.3Hz,1H),5.70(s,1H),5.42(s,1H),5.41(d,J=4.7Hz,1H),4.99(s,1H),4.47(dd,J= 8.5,4.6Hz,1H),4.25-4.10(m,4H),3.95(t,J=3.8Hz,2H),3.85(ddd,J=8.2,4.8,3.2Hz,1H),2.32(s,3H) ,2.30(s,3H),1.31(s,9H),1.30-1.24(m,6H),1.13-1.07(m,7H),1.07-1.01(m,14H),1.01-0.96(m,7H); 13 C NMR (100MHz, CDCl3) δ171.8,167.2,167.1,145.5,145.2,136.7,132.4,129.5,128.1,126.3,124.8,105.2,98.8,98.7,86.6,81.8,78.1 ,77.1,72.15,62.8,60.7,60.1,40.1,30.95,28.4,19.55,19.5,17.6,17.45,17.15,17.0,14.5,13.3,13.25,12.8,12.7.HRMS(ESI)m / z calcd forC 43 H 66 NO 10 SSi2[M+H] + :844.3941; found:844.3945.

[0066] (4) Synthesis of base J(DJ)7

[0067]

[0068] Donor 1a (117 mg, 0.152 mmol) and receptor 2 (42 mg, 0.296 mmol) were dissolved in a dry mixture of dichloromethane and hexafluoroisopropanol (7.5 mL, v / v = 3:1), and then freshly activated (dried with an alcohol torch for 3–10 minutes, the same below) was added. Molecular sieve (500 mg) was stirred at room temperature for 15 minutes, then catalyst PPh3AuNTf2 (22 mg, 0.030 mmol) was added. The reaction was stirred at room temperature for 4 hours, and TLC analysis showed that the reaction was complete. The mixture was filtered, evaporated to dryness, and then subjected to column chromatography.

[0069] (EA:PE:DCM = 2:1) yielded 3 (54.8 mg, 50%) of a white, foamy solid. [α] D 25 = +23.0(c 1.1, CHCl3), 1 HNMR(400MHz, CDCl3)δ9.76(s,2H),8.03-7.96(m,2H),7.96-7.86(m,4H),7.8 6-7.78(m,2H),7.54-7.20(m,13H),5.95(t,J=9.6Hz,1H),5.74(t,J=9.6Hz,1 H),5.56(dd,J=9.6,7.7Hz,1H),5.08(d,J=7.8Hz,1H,H-1”),4.68(dd,J=12.3 ,2.8Hz,1H),4.61(d,J=13.2Hz,1H),4.55-4.44(m,2H),4.21(d,J=9.8Hz,1H). 13 C NMR (100MHz, CDCl3) δ166.3,165.9,165.5,165.4,163.5,152.3,139.7,133.6,133.5,133.4,133.3,130.0,129.9 (2C),129.6,129.2,128.9,128.9,128.6,128.4,110.9,101.5,73.0,72.5,72.2,69.7,64.6,63.0.HRMS(ESI)m / z calcd for C 39 H 32 N2O 12 Na[M+Na] + :743.1847; found:743.1857.

[0070] Receptor 3 (45 mg, 0.062 mmol) and donor 4 (79 mg, 0.094 mmol) were dissolved in dry dichloromethane (4.6 mL), and freshly activated [product name missing] was added to the solution. Molecular sieve (400 mg) was stirred at room temperature for 15 minutes, followed by the addition of catalyst PPh3AuNTf2 (14 mg, 0.0188 mmol). The reaction was continued for 4 hours, then filtered to dryness and subjected to column chromatography.

[0071] (Petroleum ether / ethyl acetate = 3:1) isolated to give compound 5 (70 mg, 82%), a white, foamy solid. [α] D 25 =+19.0(c

[0072] 1.0,CHCl3), 1 H NMR (400MHz, CDCl3) δ9.01 (s, 1H), 8.02 (d, J = 7.6Hz, 2H), 7.89 (dd, J = 7.8, 3. 3Hz,4H),7.82(d,J=7.7Hz,2H),7.57(s,1H),7.55-7.24(m,12H),6.47(s,1H) ),5.91(t,J=9.7Hz,1H),5.68(t,J=9.7Hz,1H),5.47(dd,J=9.8,7.9Hz,1H), 5.37(s,1H,H-1'),5.24(d,J=5.2Hz,1H,H-2'),5.16(d,J=8.0Hz,1H,H-1”), 5.01(s,1H),4.63(dd,J=12.2,3.1Hz,1H),4.56(d,J=12.6Hz,1H),4.50(dd, J=12.2,4.7Hz,1H),4.43(d,J=12.5Hz,1H),4.31(dd,J=9.0,5.2Hz,1H),4.2 4-4.15(m,6H),3.92(dd,J=13.3,2.7Hz,1H),3.85(d,J=9.2Hz,1H),2.32(s, 3H),2.29(s,3H),1.31-1.26(m,8H),1.08-1.07(m,7H),1.02-0.97(m,17H). 13CNMR (100MHz, CDCl3) δ171.7,167.3,167.2,166.3,165.9,165.3,165.3,162.7,149.5,146.1,146.0,139. 3,133.5,133.4,133.3,133.2,130.0,129.9,129.8,129.7,129.3,129.0,129.0,128.5(2C),128.5,128.4 ,110.9,101.8,98.4,98.3,89.7,82.2,73.1,72.4,72.1,69.8,68.0,64.7,63.2,60.1,60.0,59.7,39.7,1 9.3,19.1,17.5(2C),17.4(2C),17.1,17.0,16.9,14.6,14.5,13.4,13.0,12.7,12.6.HRMS(ESI)m / zcalcd for C 70 H 85 N4O 22 Si2[M+NH4] + :1391.5345; found:1391.5374.

[0073] Compound 5 (60 mg, 44 μmol), 4-ClPN (0.7 mg, 0.88 μmol), and adamantane thiol (0.7 mg, 4.4 μmol) were dissolved in acetonitrile (1 mL), degassed three times under a nitrogen atmosphere, and then stirred under 465 nm light for 2 hours. After the reaction was completed, the mixture was subjected to rotary cyclohexane chromatography (ethyl acetate / petroleum ether = 2:1) to give a white, foamy solid, compound 6 (38 mg, 80%). [α] D 25 =+4.0(c 1.0,CHCl3), 1H NMR (400MHz, CDCl3) δ8.63-8.38(m,1H),8.07-7.99(m,2H),7.93-7.89(m,4H),7.84-7.81(m,2H),7.55-7.47(m ,4H),7.44-7.27(m,9H),5.92(t,J=9.6Hz,1H),5.81(dd,J=7.1,3.0Hz,1H,H-1'),5.69(t,J=9.6Hz,1H),5.49(d d,J=9.7,7.8Hz,1H),5.15(d,J=7.9Hz,1H,H-1”),4.65(dd,J=12.2,2.9Hz,1H),4.52-4.42(m,4H),4.20(dd,J=9 .6,4.6Hz,1H),4.05-3.94(m,2H),3.77-3.73(m,1H),2.43-2.36(m,1H),2.26-2.20(m,1H),1.09-0.99(m,28H). 13 C NMR (100MHz, CDCl3) δ166.2,165.8,165.3,165.3,162.7,149.6,139.1,133.5,133 .3(2C),133.2,123.0,129.9(2C),129.7,129.4,129.0(2C),128.5,128.5,128.4( 2C),110.8,101.9,85.5,84.8,73.0,72.4,72.1,69.8,69.2,64.8,63.1,61.4,40. 1,17.6,17.5,17.4,17.3,17.2,17.1,17.0,13.5,13.2,12.9,12.6.HRMS(ESI)m / z calcd for C 56 H 66 N2O 16 Si₂Na[M+Na] + :1101.3843; found:1101.3848.

[0074] Compound 6 (37 mg, 0.034 mmol) was dissolved in tetrahydrofuran (2 mL), and acetic acid (16 μL, 0.28 mmol) and tetrabutylammonium fluoride (0.14 mL, 1 mmol / L) were added. The mixture was stirred at room temperature for 8 hours, and then sodium bicarbonate was added to quench the reaction. The mixture was filtered and evaporated to dryness, followed by column chromatography (CH2Cl2 / CH3OH = 10:1) to give a white solid compound (28 mg, 98%) with the silicon group removed.

[0075] The white solid compound obtained above (28 mg, 0.033 mmol) was dissolved in THF / MeOH (3 mL, V / V = 1:

[0076] 2) K2CO3 (28 mg, 0.20 mmol) was added, and the reaction was continued to be stirred at room temperature for 8 hours. After the reaction was completed, cation exchange resin (Amberlite IR120, Na-form) was added to adjust the pH of the system to about 7. The mixture was then filtered and evaporated to dryness. Column chromatography (CH2Cl2 / CH3OH = 5:1) was used to separate the white solid compound 7 (11 mg, 79%).

[0077] [α] D 25 = +20.5(c 0.9, CHCl3), 1 H NMR(600MHz,D2O)δ8.01(s,1H),6.27(td,J=6.6,2.3Hz,1H),4.62(dd,J=12.3,2.5H z,1H),4.53-4.43(m,3H),4.04(q,J=3.8Hz,1H),3.89(dd,J=12.3,2.3Hz,1H),3.84 (dt,J=12.6,3.1Hz,1H),3.76(ddd,J=12.6,4.8,2.7Hz,1H),3.70(ddd,J=12.5,5.9 ,2.6Hz,1H),3.48-3.34(m,3H),3.26(td,J=9.4,8.8,2.6Hz,1H),2.42-2.38(m,2H). 13 C NMR(150MHz,D2O)δ165.8,152.2,142.2,111.3,102.3,87.4,86.3,76.7(2C),73.7,71.0,70.3,64.9,61.8,61.4,39.6.HRMS(ESI)m / z calcd forC 16 H 24 N2O 11 Na[M+Na] + :443.1272; found:443.1276.

[0078] Example 2

[0079] (1) Synthesis of donors 1m and 1m'

[0080]

[0081] Dissolve 4 (844.2 mg, 1.0 mmol) in THF (5 mL), add HOAc (0.59 mL, 10 mmol) and TBAF (1.28 g, 5.0 mmol, tetrabutylammonium fluoride), stir until the substrate reaction is complete as detected by TLC, dilute with EtOAc, wash with saturated NaHCO3 solution, dry with colorless Na2SO4, filter, concentrate by rotary evaporation, and purify by silica gel column chromatography (petroleum ether / ethyl acetate = 1:1) to obtain a mixture of intermediates 2-ODHIN and 3-ODHIN.

[0082] The above intermediate (600 mg, 1.0 mmol) was dissolved in dry pyridine (5 mL), and BzCl (0.35 mL, 3.0 mmol) was added at 0 °C. The mixture was brought to room temperature and stirred until the substrate reaction was complete as detected by TLC. After dilution with EtOAc, the solution was washed successively with 1 M HCl and saturated brine, dried over anhydrous Na2SO4, filtered, concentrated by rotary evaporation, and purified by silica gel column chromatography (toluene / ethyl acetate = 20:1) to give a white foamy solid 1c (401 mg, 50%) and a white foamy solid 1c' (401 mg, 50%). 1c:[α] D 25 = -60.5 (c 1.1, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.05-8.00(m,2H),8.00-7.94(m,2H),7.60-7.53(m,1H),7.53-7.47(m,2H),7.46-7.40(m,2H),7. 39-7.32(m,3H),7.20(td,J=7.7,1.6Hz,1H),7.14(dd,J=7.6,1.3Hz,1H),5.75(dd,J=6.6,4.7Hz,1H),5.69(s,1H),5.6 5(d,J=2.4Hz,1H),5.61(dd,J=4.7,2.3Hz,1H),4.97(s,1H),4.62(dd,J=10.7,3.4Hz,1H),4.59-4.49(m,2H),4.13(q,J =7.1Hz,2H),4.05(q,J=7.1Hz,2H),2.20(s,3H),2.10(s,3H),1.32(s,9H),1.22(t,J=7.1Hz,3H),1.16(t,J=7.1Hz,3H). 13C NMR(100MHz,CDCl3)δ172.1,167.0,166.3,165.4,145.75,145.6,136.05,133.5,133.15,132.6,130.1,129.9(2C),129.7,129.3,129.1,128.7(2C),128.5,128.4,128.3,126.7,125.2,105.2,98.3,98.1,87.7,79.3,76.0,72.7,64.2,60.2(2C),40.2,31.0,29.8,28.4,19.4,19.2,14.5,14.4.HRMS(ESI)m / z calcd for C 45 H 47 NO 11 SNa[M+Na] + :832.2762;found:832.2781.

[0083] 1c’:[α] D 25 =-29.3(c 1.2,CHCl3); 1 H NMR(400MHz,CDCl3)δ8.12-8.07(m,2H),8.07-7.99(m,2H),7.61-7.50(m,3H),7.49-7.40(m,4H),7.32(dd,J=7.5,1.7Hz,1H),7.18-7.05(m,2H),5.87(s,1H),5.71(d,J=4.4Hz,1H),5.68(t,J=4.5Hz,1H),5.60(t,J=5.0Hz,1H),4.90(s,1H),4.60(dd,J=12.0,3.3Hz,1H),4.52-4.46(m,1H),4.41(dd,J=12.0,4.4Hz,1H),4.18-4.06(m,2H),4.06-3.90(m,2H),2.18(s,3H),2.03(s,3H),1.25-1.18(m,12H),1.12(t,J=7.1Hz,3H); 13C NMR (100MHz, CDCl3) δ172.6,167.0,166.8,166.3,165.0,146.1,145.9,135.6 ,133.7,133.5,133.2,132.5,130.7,130.2,130.1,130.0,129.7,129.35,128 .5(2C),128.1,126.9,125.6,105.1,98.2,97.8,87.1,80.6,77.1,75.2,72.2 ,64.1,60.2,60.05,40.2,30.85,28.3,19.3,19.1,14.5,14.4.HRMS(ESI)m / z calcdfor C 45 H 47 NO 11 SNa[M+Na] + :832.2762; found:832.2773

[0084] (2) Synthesis of bases J(DJ)7 and 7'

[0085]

[0086] In a sealed tube, compound 1c (137 mg, 0.169 mmol) and receptor 8 (128 mg, 0.338 mmol) (compounds Di, Z.; Liang, X.; Xia, W.; Ya-Ming, L.; Jun-Lin, J.; Ke-Liang, L. NUCLEOS. NUCLEOT. NUCL. 2009, 28(10), 924–942.) were dissolved in dry dichloromethane (10 mL). BSTFA (178 μL, 0.676 mmol) was added, and the mixture was stirred at 80 °C for 8 hours. After cooling to room temperature, BSTFA was added to the solution. 500 mg of molecular sieve and 0.0338 mmol of PPh3AuNTf2 were added and stirred at room temperature for 1 hour. After the reaction was complete, the mixture was filtered and evaporated to dryness. Column chromatography (PhMe:MeCN = 6:1) gave a white solid compound 9 (166 mg, 98%): [α] D 25 =-4.6(c

[0087] 1.0, CHCl3); 1H NMR(400MHz, CDCl3)δ9.99(s,1H),8.11-8.04(m,2H),8.04-7.95(m,2H),7.68-7. 58(m,5H),7.53-7.32(m,11H),7.19-7.16(m,1H),6.78(s,1H),5.98(d,J=4.4Hz,1 H),5.60(t,J=5.8Hz,1H),5.49(dd,J=6.1,4.4Hz,1H),4.93(s,1H),4.66-4.40(m, 5H),4.15-3.97(m,4H),2.20(s,3H),2.15(s,3H),1.22-1.11(m,6H),1.07(s,9H); 13 CNMR (100MHz, CDCl3) δ172.2,167.0,166.9,166.0,165.15,162.3,150.5,146.95,146.7,137.9,1 36.2,135.55,135.5,133.7,133.4,132.8,132.7,130.1,130.0,129.8,129.6,129.3,129.1,129,0 ,128.9,128.6,128.5,128.5,128.3,128.2,128.0(2C),125.4,115.4,97.5,97.4,89.2,79.6,77. 4,73.5,71.0,63.9,60.1,60.0,58.9,40.2,26.9,21.5,19.3,19.0,18.9,14.4(2C).HRMS(ESI)m / z calcd for C 54 H 57 N3O 14 SiNa[M+Na] + :1022.3502; found:1022.3502.

[0088] In a sealed container, compound 1c' (101 mg, 0.124 mmol) and receptor 8 (94 mg, 0.248 mmol) were dissolved in dry dichloromethane (7 mL), and BSTFA (139 μL, 0.496 mmol) and PPh3AuNTf2 were added.

[0089] (0.0248 mmol), reacted at 80°C for 8 hours, cooled to room temperature, and then added to it. 400 mg of molecular sieve was added, and the reaction was continued with stirring at room temperature for 1 hour. After the reaction was completed, the mixture was filtered and evaporated to dryness. Column chromatography (toluene / acetonitrile = 7:1) gave a white solid compound 9' (122.8 mg, 99%). [α] D 25 = -12.2 (c 1.5, CHCl3); 1 H NMR(400MHz, CDCl3)δ10.05(br s,1H),8.13-7.95(m,2H),7.93-7.77(m,2H),7.64-7.51(m,6H),7.49-7.30(m,11H),6.92(d ,J=11.9Hz,1H),6.25(dd,J=7.2,1.2Hz,1H),5.51(dd,J=4.9,2.3Hz,1H),5.45(dd,J=7.2,4 .9Hz,1H),4.95(s,1H),4.56(dd,J=12.2,4.7Hz,1H),4.51-4.40(m,3H),4.32(dd,J=14.2,1 .5Hz,1H),4.23-4.08(m,4H),2.26(s,3H),2.08(s,3H),1.23(t,J=7.1Hz,6H),0.99(s,9H); 13 C NMR (100MHz, CDCl3) δ171.8,167.3,167.1,165.9,165.6,161.85,151.5,147.1,147.0, 138.0,135.6,135.5,135.2,133.7,133.6,132.8,132.7,130.1,130.05,129.9,129.3, 129.15,128.7,128.6(2C),128.3,127.95,125.4,115.8,97.8,85.8,80.8,73.85,71.5 ,64.1,60.1,58.9,40.6,29.8,26.8,21.6,19.2,19.1,18.9,14.6,14.5.HRMS(ESI)m / z calcd for C 54 H 57 N3O 14 SiNa[M+Na] + :1022.3502; found:1022.3526.

[0090] Dissolve 9 (166 mg, 0.165 mmol) in THF (3 mL), add HOAc (0.12 mL, 1.98 mmol) and TBAF (260 mg, 0.99 mmol), stir until the substrate reaction is complete as detected by TLC, dilute with EtOAc, wash with saturated NaHCO3 solution, dry with colorless Na2SO4, filter, concentrate by rotary evaporation, and purify by silica gel column chromatography (dichloromethane / methanol = 20:1) to obtain the product deprotected from TBDPS.

[0091] The deprotected compound (38 mg, 0.05 mmol) and donor 1a (46 mg, 0.06 mmol) obtained in the previous step were dissolved in dry dichloromethane (3 mL), and freshly activated [material / material] was added to the solution. Molecular sieve (200 mg) was stirred at room temperature for 15 minutes, followed by the addition of catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol). The reaction was continued for 1 hour, then filtered to dryness, and separated by column chromatography (petroleum ether:dichloromethane:ethyl acetate = 2:2:1) to give solid compound 10 (54.2 mg, 81%). [α] D 25 = -7.3 (c 1.0, CHCl3); 1 H NMR (600MHz, CDCl3) δ8.61(s,1H),8.11-8.03(m,4H),7.99(d,J=7.9Hz,2H),7.92-7.85(m,4H),7.82(d,J=7.9Hz,2H),7.61(d,J=7. 9Hz,1H),7.57-7.40(m,10H),7.40-7.27(m,8H),6.22(s,1H),5.95(d,J=4.2Hz,1H),5.85(t,J=10.0Hz,1H),5.69(q,J=4.6Hz,1H), 5.57(t,J=10.1Hz,1H),5.53(q,J=4.8Hz,1H),5.31(t,J=9.2Hz,1H),4.95(d,J=8.0Hz,1H),4.90(s,1H),4.74-4.64(m,2H),4.59(d ,J=12.3Hz,1H),4.56-4.44(m,2H),4.36(s,2H),4.18-3.94(m,5H),2.24-2.11(m,6H),1.21(t,J=7.9Hz,3H),1.13(t,J=7.9Hz,3H); 13C NMR (150MHz, CDCl3) δ172.15,166.9,166.8,166.3,166.2,166.0,165.4,165.3,165.2,161.9, 149.7,146.6,146.3,138.3,133.8,133.6,133.4,133.3,130.2,130.0,129.9(2C),129.7,129 .6,129.35,129.1,128.9(2C),128.7,128.5(2C),111.8,101.2,97.8,88.5,80.45,73.3,72.9 ,72.4,71.9,71.15,69.9,64.3,63.8,63.3,60.2,60.1,40.3,19.2,14.5,14.4.HRMS(ESI)m / z calcdfor C 72 H 66 N3O 23 [M+H] + :1340.4082; found:1340.4082.

[0092] Following the same reaction steps as in 9 to 10, 9' (50 mg, 0.050 mmol) can be converted into a white solid 10' (50.4 mg, 75%): [α] D 25 = +8.0 (c 1.0, CHCl3); 1 H NMR (400MHz, CDCl3) δ9.29 (s, 1H), 8.17-8.09 (m, 2H), 7.98-7.94 (m, 2H), 7.92 (d, J = 7.7Hz, 2H), 7.90-7.80 (m, 6H), 7.62-7. 47(m,8H),7.46-7.40(m,2H),7.40-7.33(m,5H),7.33-7.27(m,4H),6.42(s,1H),6.16(d,J=5.9Hz,1H),5.85(t,J=9.7Hz,1 H),5.60-5.43(m,3H),5.18(dd,J=9.8,7.8Hz,1H),4.95(s,1H),4.90(d,J=7.8Hz,1H),4.67(t,J=2.9Hz,2H),4.57(dd,J=1 2.2,3.1Hz,1H),4.48-4.35(m,3H),4.29(d,J=13.0Hz,1H),4.19-4.08(m,5H),2.21(s,3H),2.15(s,3H),1.27-1.20(m,6H); 13CNMR(100MHz, CDCl3)δ172.1,167.1(2C),166.3,166.2,165.9,165.6,165.4,165.0,161.8,

[0093] 150.7, 146.7, 146.5, 133.7, 133.6, 133.4, 133.3, 130.2, 130.0, 129.9, 129.8, 129.6, 129.3, 129.0,

[0094] 128.9(2C),128.7(2C),128.7,128.55,128.5(2C),112.3,101.25,98.1,97.9,86.3,81.1,73.9,72.7 ,72.4,71.8,71.7,69.8,64.1,63.3,60.3,60.2,40.6,19.25,19.15,14.6,14.5.HRMS(ESI)m / zcalcd for C 72 H 66 N3O 23 [M+H] + :1340.4082; found:1340.4083.

[0095] Compound 10 (50 mg, 0.037 mmol), 4-ClPN (0.6 mg, 0.74 μmol), and adamantane thiol (1.2 mg, 7.4 μmol) were dissolved in acetonitrile (1 mL), degassed three times under an inert gas atmosphere, and then stirred under 465 nm light for 4 hours. After the reaction was completed, the mixture was subjected to rotary cyclohexane chromatography (EA / PE = 2:1) to give a white, foamy solid, compound 11 (31.2 mg, 80%). [α] D 25 = +3.3(c 0.5, CHCl3), 1H NMR(400MHz,CDCl3)δ8.11-8.03(m,4H),8.03-7.99(m,3H),7.95-7.87(m,4H),7.84-7.80(m,2H),7.65-7.58(m,2H),7.56-7.32(m,15H),7.29(d,J=7.8Hz,2H),6.28(dd,J=8.3,5.6Hz,1H),5.89(t,J=9.7Hz,1H),5.63(t,J=9.7Hz,1H),5.58(d,J=6.4Hz,1H),5.38(dd,J=9.8,7.9Hz,1H),4.98(d,J=7.9Hz,1H),4.78-4.67(m,2H),4.63(dd,J=12.0,3.0Hz,1H),4.54(d,J=2.7Hz,1H),4.48-4.42(m,2H),4.27(d,J=12.9Hz,1H),4.11(dd,J=7.5,3.4Hz,1H),2.68(dd,J=14.4,5.6Hz,1H),2.35(dt,J=14.7,7.4Hz,1H). 13 C NMR(150MHz,CDCl3)δ166.3,166.2,166.0,165.9,165.3,165.15,161.9,149.7,137.5,133.8,133.7,133.6,133.4,133.3,130.0,129.95,129.9(2C),129.7(2C),129.6,129.4,

[0096] 129.25,129.0(2C),128.9,128.7,128.6,128.5,128.4,111.8,101.8,85.9,83.1,75.2,72.9,72.5,71.95,69.7,64.6,64.4,63.1,38.3.HRMS(ESI)m / z calcd forC 58 H 49 N2O 17 [M+H] + :1045.3026;found:1045.3026.

[0097] Compound 10' (66 mg, 0.05 mmol), 4-ClPN (0.8 mg, 0.98 μmol), and adamantane thiol (1.7 mg, 100 μmol) were dissolved in acetonitrile (1 mL), degassed three times under an inert gas atmosphere, and then stirred under 465 nm light for 4 hours. After the reaction was completed, the mixture was subjected to rotary evaporation column chromatography (EA / PE = 2:1) to give a white, foamy solid compound 11' (41.7 mg, 81%). [α] D 25 = -4.5 (c 0.5, CHCl3), 1 H NMR(600MHz, CDCl3)δ8.34(s,1H),8.08-8.04(m,4H),8.03-7.99(m,2H),7.91( ddd,J=8.5,5.4,1.4Hz,4H),7.85-7.79(m,2H),7.62-7.57(m,1H),7.55-7.40( m,10H),7.39(t,J=7.8Hz,2H),7.34(t,J=7.8Hz,2H),7.31-7.26(m,4H),5.92( t,J=9.7Hz,1H),5.84(d,J=1.9Hz,1H),5.68(t,J=9.7Hz,1H),5.63(dt,J=6.5,

[0098] 1.8Hz,1H),5.49(dd,J=9.8,7.9Hz,1H),5.02(d,J=7.9Hz,1H),4.73-4.67(m,2H),4.65(dd,J=12.2,3.1Hz,1H),4.57-4.51(m,2H),4.47(dd,J=12 .2,5.0Hz,1H),4.39(d,J=13.2Hz,1H),4.17(ddd,J=9.9,5.0,3.2Hz,1H),2.46(ddd,J=13.8,10.2,6.4Hz,1H),2.31(ddd,J=13.9,5.5,1.7Hz,1H). 13 C NMR (150MHz, CDCl3) δ166.4,166.3,165.9,165.7,165.3(2C),

[0099] 162.05,149.5,138.6,133.8,133.6,133.5,133.4,133.4,133.3,130.0(2C),129.9(2C),129.7,

[0100] 129.3(2C),129.0,128.9,128.7,128.55,128.5,128.4,111.4,101.6,92.4 ,78.4,78.2,72.9,72.5,72.0,69.7,65.1,64.6,63.0,33.5.HRMS(ESI)m / z calcd for C 58 H 49 N2O 17 [M+H] + :1045.3026; found:1045.3026.

[0101] Dissolve 11 (32 mg, 0.031 mmol) in THF / MeOH (3 mL, V / V = 1:2), add K2CO3 (39 mg, 0.28 mmol), and continue stirring at room temperature for 8 hours. After the reaction is complete, add cation exchange resin (Amberlite IR120, Na-form) to adjust the pH of the system to about 7, then filter and evaporate to dryness. Separate 7 (12.7 mg, 99%) by column chromatography (CH2Cl2 / CH3OH = 3:1).

[0102] 11' (40 mg, 0.038 mmol) was dissolved in THF / MeOH (3 mL, V / V = 1:2), and K2CO3 (47 mg, 0.34 mmol) was added. The mixture was then stirred at room temperature for 8 hours. After the reaction was complete, cation exchange resin (Amberlite IR120, Na-form) was added to adjust the pH of the system to approximately 7. The mixture was then filtered, evaporated to dryness, and separated by column chromatography (CH2Cl2 / CH3OH = 3:1) to obtain 7' (15.3 mg, 95%). [α] D 25 = -30.4 (c 0.4, CH3OH), 1H NMR(600MHz,D2O)δ8.03(s,1H),5.64(s,1H),4.44(d,J=12.2Hz,1H),4.40-4.29(m,4H),3.84(dd,J=13.0,2.6Hz,1H),3.72(d,J=12.3Hz,1H),3.61(dd,J=13.2,3.9Hz,1H),3.54(dd,J=12.5,5.8Hz,1H),3.30(t,J=9.1Hz,1H),3.25(t,J=7.9Hz,1H),3.20(t,J=9.3Hz,1H),3.09(t,J=8.8Hz,1H),1.90(td,J=12.6,10.9,5.3Hz,1H),1.83(dd,J=14.0,5.6Hz,1H). 13 C NMR(150MHz,D2O)δ165.15,151.3,141.1,109.6,101.4,92.3,81.8,75.9,75.6,75.45,72.9,69.45,64.2,61.4,60.6,32.0.HRMS(ESI)m / z calcd for C 16 H 24 N2O 11 Na[M+Na] + :443.1272;found:443.1272。

Claims

1. A method for synthesizing β-D-glucosyl-5-hydroxymethyluracil, characterized in that, Includes the following steps: R1 is selected from Bz, Ac, CA, Lev, TBDPS, TBS, Ts, All, Nap, or Bn; R2 is selected from Bz, Ac, Boc, CA, or Lev. (1) Compound 1a and Compound 2 were dissolved in an organic solvent, and Compound 3 was obtained in the presence of a desiccant and a catalyst; (2) Compounds 3 and 4 were dissolved in an organic solvent and, in the presence of a desiccant and a catalyst, compound 5 was obtained. (3) Compound 5, 4CzlPN and adamantane thiol were dissolved in an organic solvent and reacted completely under a protective atmosphere and under blue LED light to obtain compound 6. (4) Compound 6 was deprotected to obtain compound 7. In steps (1) and (2), the catalyst is a monovalent gold complex and the desiccant is a molecular sieve.

2. A method for synthesizing β-D-glucosyl-5-hydroxymethyluracil, characterized in that, Includes the following steps: R1 and R5 are selected from Bz, Ac, CA, Lev, TBDPS, TBS, Ts, All, Nap, or Bn; R2 is selected from Bz, Ac, Boc, CA, or Lev. S1. Remove the silicon-based protecting group from compound 4 and protect it with the R5 protecting group to obtain 1c and 1c'; wherein, compound 4 is first subjected to the removal of the silicon-based protecting group under the action of acetic acid and tetrabutylammonium fluoride, and the molar ratio of compound 4, acetic acid and tetrabutylammonium fluoride is 1:(5~15):(3~8). S2. Compound 1c or 1c' and compound 8 are dissolved in an organic solvent, and 9 and 9' are obtained under the action of a drying agent, an accelerator and a catalyst. S3. After removing TBDPS protection from 9 or 9', it is dissolved in an organic solvent along with compound 1a, and under the action of a drying agent and a catalyst, compounds 10 and 10' are obtained. S4. Dissolve compound 10 or 10', 4CzlPN and adamantane thiol in an organic solvent, and stir the reaction under a protective atmosphere and under blue LED light to obtain compound 11 or 11'. S5. Remove the protecting group from compound 11 or 11' to obtain compound 7 or 7'; In steps S2 and S3, the catalyst is a monovalent gold complex, the promoter is BSTFA or NIS, and the desiccant is a molecular sieve.

3. The synthesis method according to claim 1, characterized in that, In step (1), the molar ratio of compound 1, compound 2 and catalyst is 1:(1.5~2.5):(0.1~0.3), and the amount of molecular sieve added is 1.5~2.0 g / mmol based on compound 2; in step (2), the molar ratio of compound 3, compound 4 and catalyst is 1:(1~2):(0.2~0.4), and the amount of molecular sieve added is 5~8 g / mmol based on compound 3; in step (3), the molar ratio of compound 5, 4CzlPN and adamantane thiol is 1:(0.01~0.03):(0.1~0.2), the wavelength of the blue LED light is 430~500nm, and the organic solvent is at least one of ethyl acetate, tetrahydrofuran, toluene and acetonitrile.

4. The synthesis method according to claim 2, characterized in that, In step S2, the molar ratio of compound 1c or 1c', compound 8, promoter and catalyst is 1:(1~2):(4~8):(0.02~0.2); the amount of molecular sieve added is 1~2 g / mmol based on compound 8; in step S3, the molar ratio of the deprotected compound and compound 1a is 1:(1~1.5), the molar ratio of compound 1a and catalyst is 1:(0.02~0.2), and the amount of molecular sieve added is 3~5 g / mmol based on the deprotected compound; in step S4, the molar ratio of compound 10 or 10', 4CzlPN and adamantane mercaptan is 1:(0.01~0.03):(0.2~2), the wavelength of the blue LED light is 430~500 nm, and the organic solvent is at least one of ethyl acetate, tetrahydrofuran, toluene and acetonitrile.

5. The synthesis method according to claim 1 or 2, characterized in that, The preparation process of compound 4 is as follows: G1 is selected from Bz, Ac, CA, Lev, TBDPS, TBS, Ts, All, Nap or Bn, G2 is selected from Bz, Ac, Boc, CA or Lev, and X is Cl, Br or I. The specific synthesis process is as follows: a. Compound S2 and 2-halogenated thiophenol were reacted under Lewis acid conditions to give compound S3; b. Compound S3 and 3,3-dimethyl-1-butyne undergo a Sonogashira reaction to give compound 1b; c. Compound 1b was reduced to obtain a triol intermediate; the triol intermediate was reacted with TIPSCl to obtain compound S4; d. Compound S4 and DHPCOOH were subjected to esterification to obtain compound 4.

6. The synthesis method according to claim 5, characterized in that, In step a, the molar ratio of compound S2, 2-halogenated thiophenol, and Lewis acid is 1:(1.5~2):(2~3); in step b, the Sonogashira reaction includes the following steps: dissolving compound S3, Ph3P, Pd(PPh3)2Cl2, and CuI in an organic solvent, cooling to -78℃ to -40℃ in an inert gas atmosphere, adding 3,3-dimethyl-1-butyne, heating to 50~100℃, and reacting until TLC shows complete reaction. The organic solvent is selected from one or more of N,N-dimethylformamide, diisopropanolamine, tetrahydrofuran, dichloromethane, acetone, and toluene; in step c, the molar ratio of the triol intermediate and TIPSCl is 1:(1~1.5).

7. The synthesis method according to claim 1 or 2, characterized in that, The preparation process of compound 1a is as follows: R1 is selected from Bz, Ac, CA, Lev, TBDPS, TBS, Ts, All, Nap, or Bn; R2 is selected from Bz, Ac, Boc, CA, or Lev; X is Cl, Br, or I; and compound S1 undergoes a Sonogashira reaction with 3,3-dimethyl-1-butyne to give compound 1a.

8. According to the synthesis method of claim 3, in step (1), hexafluoroisopropanol is added to the organic solvent, and the volume ratio of the organic solvent to hexafluoroisopropanol is (3~5):

1.

9. The β-D-glucosyl-5-hydroxymethyluracil compound prepared by the synthetic method according to any one of claims 2, 4 to 7, characterized in that, The structure is .

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