Vaccine adjuvant Sulfavant A synthesis method

Abstract

The invention discloses a method for synthesizing a vaccine adjuvant Sulfavant A. The method relates to the technical field of vaccine adjuvant synthesis, and comprises the following steps: selectively removing-OAc groups on different-head carbon in a compound 3 to obtain a compound 4; the compound 4 is subjected to a Schmidt glycosylation reaction to obtain a compound 6, and the reaction formula is as follows: # imgabs0 #, THF is tetrahydrofuran; the DBU is 1, 8-diazabicyclo undec-7-ene, and the DBU is 1, 8- DCM is dichloromethane; the TFK is trifluoroacetone. According to the method, the defects of an existing synthesis route are overcome, the synthesis efficiency and the yield are improved, the cost is reduced, and the post-treatment process is simplified.

Description

Technical Field

[0001] The invention relates to the technical field of vaccine adjuvant synthesis, and in particular to a method for synthesizing vaccine adjuvant Sulfavant A. Background Art

[0002] Vaccine adjuvants are important ingredients that enhance the immunogenicity of vaccines and improve the protective effects of vaccines. Traditional vaccine adjuvants such as aluminum salts and emulsifiers have certain limitations, which may cause adverse reactions and affect the stability of vaccines. Therefore, it is of great significance to develop new, safe and efficient vaccine adjuvants.

[0003] Sulfonylquinol diacylglycerol (SQDG) is composed of a sulfonylquinol sugar head group, two fatty acid chains and a glycerol backbone. It has a unique chemical structure and biological activity. The structural formula is as follows: .

[0004] Studies have shown that SQDG plays an important role in the defense against pathogens. In plants, when invaded by pathogens, the SQDG content or structure on the cell membrane may change, which may activate the plant's defense mechanism, such as inducing the expression of defense-related genes and synthesizing anti-pathogen substances. Therefore, SQDG has broad potential application value and market prospects in the fields of medicinal chemistry and vaccine technology. However, it is difficult to separate and purify SQDG from natural sources, and the unavailability of chemical standards on the market limits its application. Therefore, it is of great significance to develop an effective method for the chemical synthesis of SQDG.

[0005] 1) Patent application document 1: WO2022 / 034429 A1 discloses a synthetic route of sulfoquinolose-diacylglycerol Sulfavant A: This method has the following defects: a) After each step of the experimental reaction, silica gel column chromatography is required for separation and purification, which will inevitably waste a lot of time and cause waste of experimental products, resulting in a low overall yield; b) Preparation of Compound 4 to Compound 5, Compound 6 to Compound 7. These two steps of reaction are often incomplete and produce a large number of by-products, which affect the synthesis of Compound 5 and Compound 7 and result in a low yield; c) 2-Butanone is used in the synthesis of compound 8. This reagent is relatively dangerous and requires extreme caution when handling.

[0006] 2) Patent application document 2: CN117164649A discloses a synthetic route of sulfoquinolose-diacylglycerol Sulfavant A: This method has the following defects: a) After each step of the experimental reaction, silica gel column chromatography is required for separation and purification, which will inevitably waste a lot of time and cause waste of experimental products, resulting in a low overall yield; b) In the preparation of compound 4 to compound 5 and compound 5 to compound 6, expensive metal reagents such as titanium tetrabromide and silver trifluoromethanesulfonate were used, which increased the material cost.

[0007] In summary, in the existing process for preparing Sulfavant A, there are problems such as selective protection and selective removal of protective functional groups, all intermediate products need to be separated and purified by silica gel column chromatography, and some reagents used are expensive and dangerous, resulting in a long production process and a low total yield of the experiment. Therefore, it can only be applied to gram or kilogram production and cannot be applied to large-scale industrial production. Summary of the invention

[0008] To address the deficiencies of the prior art, the present invention provides a method for synthesizing a vaccine adjuvant Sulfavant A, which improves the deficiencies of the existing synthesis route, improves the synthesis efficiency and yield, reduces the cost, and simplifies the post-processing process.

[0009] In order to achieve the purpose of the present invention, the following scheme is proposed: First, the names and structures of the compounds involved in this scheme are described: D-Glucose structural formula: ; The name of compound 2 is 6-O-p-toluenesulfonyl-1,2,3,4-tetra-O-acetyl-D-glucose, and the structural formula is: ; The name of compound 3 is 6-thioacetyl-1,2,3,4-tetra-O-acetyl-D-glucose, and the structural formula is: ; The name of compound 4 is 6-thioacetyl-2,3,4-tri-O-acetyl-D-glucose, and the structural formula is: ; The name of compound 6 is 1,2-O-isopropylidene-3-O-β-[(6-thioacetyl-2,3,4-tri-O-acetyl)-D-glucosyl]-R / S-glycerol, and the structural formula is: ; The name of compound 7 is 3-O-β-[(6-thioacetyl-2,3,4-tri-O-acetyl)-D-glucosyl]-R / S-glycerol, and the structural formula is: ; The name of compound 8 is 1,2-O-distearoyl-3-O-β-[(2,3,4-tri-O-acetyl-6-thioacetyl)-D-glucosyl]-R / S-glycerol, and the structural formula is: ; Compound 9 is named as 1,2-O-distearoyl-3-O-β-(2,3,4-tri-O-acetyl)-D-sulfoquinolose-R / S-glycerol potassium salt, with the structural formula: ; Sulfavant A is 1,2-O-distearoyl-3-O-β-D-sulfoquinol-R / S-glycerol sodium salt, with the structural formula: .

[0010] A method for synthesizing vaccine adjuvant Sulfavant A comprises the following steps: The -OAc group on the anomeric carbon in compound 3 is selectively removed to obtain compound 4; compound 4 is subjected to Schmidt glycosylation reaction to obtain compound 6, and the reaction formula is as follows: Among them, THF is tetrahydrofuran; DBU is 1,8-diazabicycloundec-7-ene; DCM is dichloromethane; TFK is trifluoroacetone.

[0011] Further, the method for synthesizing compound 3 in this scheme is referred to CN117164649A, specifically: the 6th hydroxyl group of D-glucose is introduced with a -Ts protecting group, the remaining hydroxyl groups are introduced with -Ac protecting groups, and the -SAc protecting group replaces the -Ts protecting group to obtain compound 3, and the reaction formula is as follows: Among them, -Ts is p-toluenesulfonyl; -Ac is acetyl; -SAc is thioacetyl; Py is pyridine; TsCl is p-toluenesulfonyl chloride; DMF is dimethylformamide; Ac2O is acetic anhydride.

[0012] Furthermore, the steps for synthesizing compound 4 are as follows: dissolving compound 3 in tetrahydrofuran, adding benzylamine, and stirring at 20°C overnight; after the reaction is completed, adding water to quench the reaction, extracting with ethyl acetate, and drying and concentrating the organic phase; purifying the crude product by a chromatographic column to obtain compound 4, wherein the ratio of petroleum ether to ethyl acetate in the chromatographic column is 1:2.

[0013] Furthermore, the steps for synthesizing compound 6 are as follows: dissolving compound 4 in dichloromethane, adding 1,8-diazabicycloundec-7-ene, replacing the atmosphere with nitrogen three times, cooling to -30°C and slowly dropping trichloroacetonitrile, maintaining -30°C and stirring for 1 hour after the addition is complete, and monitoring the reaction on a plate until compound 4 is completely consumed; then adding trifluoroacetone, acetone glycerol acetal and 4A molecular sieves, replacing the atmosphere with nitrogen three times, cooling to -30°C and slowly dropping boron trifluoride etherate, maintaining -30°C and stirring for 1 hour after the addition is complete, after the reaction is complete, adding triethylamine to quench the reaction, extracting with ethyl acetate, drying and concentrating the organic phase, and purifying the crude product by a chromatographic column to obtain compound 6, wherein the ratio of petroleum ether to ethyl acetate in the chromatographic column is 2:1.

[0014] Further, the method for synthesizing Sulfavant A from compound 6 in this scheme is described in WO2022 / 034429 A1, specifically: selectively opening the acetal protecting group of compound 6 to obtain compound 7; condensing compound 7 with stearic acid to obtain compound 8; oxidizing the -SAc protecting group of compound 8 to -SO3 - , compound 9 is obtained; the peracetyl protecting group of compound 9 is removed, and then compound Sulfavant A is obtained by passing through a sodium ion exchange resin. The reaction formula is as follows: .

[0015] The beneficial effects of the present invention are: 1. Low material cost: The materials required in the entire synthesis process are cheap and easy to obtain, which reduces the material cost.

[0016] 2. Mild reaction conditions: The reaction conditions of the entire synthesis process are mild, which is conducive to improving the yield and purity of the product.

[0017] 3. Simple post-processing: Both intermediate products are synthesized in one pot, which saves the operation time of subsequent experimental treatment and separation and purification.

[0018] 4. High synthesis efficiency: By optimizing the synthesis route, the entire reaction time is greatly shortened and the synthesis efficiency is improved.

[0019] 5. Improved yield: Compared with the traditional method, the yield of the present invention is significantly improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 shows the H NMR spectrum of compound 4; Figure 2 shows the mass spectrum of compound 4; Figure 3 shows the mass spectrum of compound 6; Figure 4 shows the H NMR spectrum of Sulfavant A; Figure 5 The mass spectrum of Sulfavant A is shown. DETAILED DESCRIPTION

[0021] like Figure 1 As shown, this embodiment provides a method for synthesizing vaccine adjuvant Sulfavant A, and the overall reaction formula is as follows: .

[0022] The specific steps are as follows: (1) D-glucose is used to synthesize compound 3. For the specific method, see paragraphs

[0057] to

[0067] of the specification of CN117164649A: A -Ts protecting group is introduced into the 6th hydroxyl group of D-glucose, and -Ac protecting groups are introduced into the remaining hydroxyl groups. The -SAc protecting group replaces the -Ts protecting group to obtain compound 3.

[0023] (2) Compound 3 was synthesized into compound 4 as follows: The first scheme: It is the preferred scheme, 17g 0.042mol compound 3 is dissolved in 350mL tetrahydrofuran, 6.72g 0.054mol benzylamine is added, and stirred at 20°C overnight; after the reaction is completed, water is added to quench the reaction, ethyl acetate is extracted, and the organic phase is dried and concentrated; the crude product is purified by a chromatographic column to obtain 14g compound 4 with a yield of 92%, wherein the ratio of petroleum ether to ethyl acetate in the chromatographic column is 1:2.

[0024] The second scheme: 17g 0.042mol compound 3 was dissolved in 350mL tetrahydrofuran, 2.52g 0.042mol ethylenediamine and 2.52g 0.042mol acetic acid were added dropwise at 10°C, and stirred overnight at 10°C; after the reaction was completed, water was added to quench the reaction, and ethyl acetate was used for extraction, and the organic phase was dried and concentrated; the crude product was purified by a chromatographic column to obtain 13.3g of compound 4 with a yield of 87%, wherein the ratio of petroleum ether to ethyl acetate in the chromatographic column was 1:2.

[0025] The third scheme: 17g 0.042mol compound 3 was dissolved in 350mL tetrahydrofuran, 2.32g 0.046mol hydrazine hydrate was added, and the mixture was stirred at 15°C overnight; after the reaction was completed, water was added to quench the reaction, and the mixture was extracted with ethyl acetate, and the organic phase was dried and concentrated; the crude product was purified by a chromatographic column to obtain 13.6g compound 4 with a yield of 90%, wherein the ratio of petroleum ether to ethyl acetate in the chromatographic column was 1:2.

[0026] The fourth scheme: 17g 0.042mol compound 3 was dissolved in 350mL tetrahydrofuran, 4.80g 0.050mol ammonium carbonate was added, and the mixture was stirred at 25°C overnight; after the reaction was completed, water was added to quench the reaction, and the mixture was extracted with ethyl acetate, and the organic phase was dried and concentrated; the crude product was purified by a chromatographic column to obtain 12.9g compound 4 with a yield of 85%, wherein the ratio of petroleum ether to ethyl acetate in the chromatographic column was 1:2.

[0027] like Figure 1 , Figure 2 As shown, the structural characterization data of compound 4: 1 H NMR (400MHz, CDCl3): δ5.52–5.50(m,2H),5.45–5.44(m,1H),5.40(dd,1H,J=3 .3,10.9Hz),5.16(dd,1H,J=3.4,10.8Hz),5.08-5.06(m,2H),4.68(dd,1H,J= 8.6,15.2Hz),4.28(m,1H),3.78-3.74(m,1H),3.67(d,1H,J=8.8Hz),3.19(d, 1H,J=1.1Hz),3.16-2.97(m,4H),2.36(s,6H),2.20,2.12,2.01(3s,18H);LCMS m / z387.1[M+Na] + .

[0028] (3) Compound 4 was synthesized into compound 6 as follows: The first scheme: which is the preferred scheme, 20g 0.055mol compound 4 is dissolved in 160mL dichloromethane, 2.51g 0.0165mol 1,8-diazabicycloundec-7-ene is added, and after nitrogen replacement 3 times, the temperature is cooled to -30°C and 15.82g 0.110mol trichloroacetonitrile is slowly added dropwise, and after the addition is completed, the temperature is kept at -30°C and stirred for 1h, and the reaction is monitored by a plate until the compound 4 is completely consumed; then 6.16g 0.055mol trifluoroacetone, 9.45g 0.0715mol acetone acetal and 6g 4A molecular sieves are added, and after nitrogen replacement 3 times, the temperature is cooled to -30°C and 1.56g 0.055mol trifluoroacetone, 9.45g 0.0715mol acetone acetal and 6g 4A molecular sieve are slowly added dropwise. 0.011 mol of boron trifluoride ether was added dropwise, and the mixture was stirred at -30 °C for 1 h. After the reaction was completed, triethylamine was added to quench the reaction. The mixture was extracted with ethyl acetate, and the organic phase was dried and concentrated. The crude product was purified by chromatographic column to obtain 21.3 g of compound 6 with a yield of 81%. The ratio of petroleum ether to ethyl acetate in the chromatographic column was 2:1.

[0029] The second solution: 20g 0.055mol compound 4 was dissolved in 160mL dichloromethane, and 2.28g 0.0165mol potassium carbonate was added. After nitrogen replacement 3 times, the temperature was cooled to -10℃ and 15.82g 0.110mol trichloroacetonitrile was slowly added dropwise. After the addition was completed, the temperature was kept at -10℃ and stirred for 1h. The reaction was monitored by the plate until the compound 4 was completely consumed; then 6.16g 0.055mol trifluoroacetone, 9.45g 0.0715mol acetone acetal and 6g 4A molecular sieve were added. After nitrogen replacement 3 times, the temperature was cooled to -10℃ and 1.56g 0.055mol trifluoroacetone, 9.45g 0.0715mol acetone acetal and 6g 4A molecular sieve were slowly added dropwise. 0.011 mol of boron trifluoride ether was added dropwise and stirred at -10 °C for 1 h. After the reaction was completed, triethylamine was added to quench the reaction. The organic phase was extracted with ethyl acetate and dried and concentrated. The crude product was purified by chromatographic column to obtain 20.3 g of compound 6 with a yield of 77%. The ratio of petroleum ether to ethyl acetate in the chromatographic column was 2:1.

[0030] The third scheme: 20g 0.055mol compound 4 was dissolved in 160mL dichloromethane, 2.51g 0.0165mol 1,8-diazabicycloundec-7-ene was added, and the temperature was cooled to -40℃ and 15.82g 0.110mol trichloroacetonitrile was slowly added dropwise. After the addition was completed, the temperature was kept at -40℃ and stirred for 1h. The reaction was monitored by the plate until the compound 4 was completely consumed; then 6.16g 0.055mol trifluoroacetone, 9.45g 0.0715mol acetone acetal and 6g 4A molecular sieve were added, and the temperature was cooled to -40℃ and 1.56g 0.055mol trifluoroacetone, 9.45g 0.0715mol acetone acetal and 6g 4A molecular sieve were slowly added dropwise. 0.011 mol of boron trifluoride ether was added dropwise, and the mixture was stirred at -40 °C for 1 h. After the reaction was completed, triethylamine was added to quench the reaction. The mixture was extracted with ethyl acetate, and the organic phase was dried and concentrated. The crude product was purified by chromatographic column to obtain 20.6 g of compound 6 with a yield of 79%. The ratio of petroleum ether to ethyl acetate in the chromatographic column was 2:1.

[0031] The fourth scheme: 20g 0.055mol compound 4 was dissolved in 160mL dichloromethane, 2.51g 0.0165mol 1,8-diazabicycloundec-7-ene was added, and the temperature was cooled to -20℃ and 15.82g 0.110mol trichloroacetonitrile was slowly added dropwise. After the addition was completed, the temperature was kept at -20℃ and stirred for 1h. The reaction was monitored by the plate until the compound 4 was completely consumed; then 6.16g 0.055mol trifluoroacetone, 9.45g 0.0715mol acetone acetal and 6g 4A molecular sieve were added, and the temperature was cooled to -20℃ and 1.56g 0.055mol trifluoroacetone, 9.45g 0.0715mol acetone acetal and 6g 4A molecular sieve were slowly added dropwise. 0.011 mol of boron trifluoride ether was added dropwise, and the mixture was stirred at -20 °C for 1 h. After the reaction was completed, triethylamine was added to quench the reaction. The mixture was extracted with ethyl acetate, and the organic phase was dried and concentrated. The crude product was purified by chromatographic column to obtain 19.8 g of compound 6 with a yield of 76%. The ratio of petroleum ether to ethyl acetate in the chromatographic column was 2:1.

[0032] like Figure 3 As shown, the structural characterization data of compound 6: 1 H NMR (400MHz, CDCl3): δ5.18(m,1H),5.00(m,2H),4.55(d,J=7.98Hz,1H),4.24(m,1H),4.03(m,2H),3.77-3.68(m,2H),3.63(m,1H),3.25(bd ,J=12.0,1H),3.05(bd,J=10.9Hz,1H),2.34(s,3H),2.09(s,3H),2.04(s,3H),2.00(s,3H),1.41(s,3H),1.34(s,3H);LCMSm / z501.1[M+Na]+ .

[0033] (4) The method for synthesizing compound 6 into Sulfavant A is described in WO2022 / 034429 A1, which is as follows: 28.7 g (0.06 mol) of compound 6 was dissolved in 200 mL of acetonitrile, to which 89.2 g (0.3 mol) of zinc nitrate hexahydrate was added, and the mixture was kept at 50°C for 6 hours under magnetic stirring. After evaporation of the organic phase, it was diluted in 200 mL of dichloromethane and extracted with 200 mL of 1 M NaHCO3 solution. The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated to obtain 19.7 g of compound 7 with a yield of 75%.

[0034] Structural characterization data of compound 7: 1 H NMR (400MHz, CDCl3): δ5.18(bt,J=9.51Hz,1H),4.99(overlapped,2H),4.52(d,J=8.01Hz,1H),3.84(overlapped,3H),3.67- 3.60(overlapped,3H),3.26(bd,1H),3.03(bd,H),2.35(s,3H),2.10(s,3H),2.05(s,3H),2.00(s,3H); LCMSm / z461.1[M+Na] + .

[0035] 19.7 g (0.045 mol) of compound 7 was dissolved in 200 mL of anhydrous dichloromethane, and 21.1 g (0.11 mol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 11.0 g (0.09 mol) of 4-dimethylaminopyridine and 28.2 g (0.1 mol) of stearic acid were added thereto. The mixture was stirred vigorously at room temperature overnight under an inert argon atmosphere. After evaporation, the mixture was purified by a chromatographic column to obtain 40.2 g of compound 8 with a yield of 92%. The ratio of petroleum ether to ethyl acetate in the chromatographic column was 4:1.

[0036] Structural characterization data of compound 8: 1H NMR (400MHz, CDCl3): δ5.41-5.39(m,1H),5.23-5.21(m,1H),5.15-5.13(overlapped,1H),5. 01-4.99(m,1H),4.93-4.91(m,1H),4.33-4.31(m,1H),4.27-4.25(m,1H),4.26-4.24(m,1H),3 .72-3.70(m,1H),3.64-3.62(m,1H),3.23-3.21(m,1H),3.12-3.10(m,1H),2.31-2.29(m,4H) ,2.04(s,6H),1.99(s,3H),1.60e1.57(m,4H),1.37-1.23(m,56H),0.89(t,J=6.3Hz,6H);LCMS m / z993.6[M+Na] + .

[0037] 20.2 g 0.021 mol of compound 8 was thoroughly mixed and dissolved with 130 mL of 80% acetic acid solution, and 2.45 g 0.025 mol of potassium acetate was added under nitrogen protection. After stirring for 10 min, 9.6 mL of 30% H2O2 solution was added and the mixture was reacted at 40°C overnight. After the reaction was complete, the mixture was concentrated under vacuum and passed through a chromatographic column (V DCM :V MeOH =99:1-4:1) to obtain 17.3 g of compound 9 with a yield of 83.1%.

[0038] Structural characterization data of compound 9: 1H NMR (400MHz, CDCl3): δ5.30 (m, 2H), 5.00-4.80 (m, 2H), 4.68 (d, J = 7.2Hz, 1H), 4.31 (dd, J = 10.8Hz, 1H), 4.15-4.00 (m, 3H), 3.75 (m, 1H), 3.20 (m, 2H), 2.33-2.28 (m, 4H), 2.06-1.98 (s, 9H), 1.64-1.55 (m, 4H), 1.34-1.22 (m, 56H), 0.91-0.88 (m, 6H); LCMS m / z 975.6 [MK] - .

[0039] 15 g 0.0147 mol of compound 9 was mixed with 600 mL 85% ethanol aqueous solution to form a suspension, 1.79 mL hydrazine hydrate was added, and the mixture was stirred at room temperature for 10 min. The mixture was then gradually heated to 40 °C, reacted for 4 h, and then stirred overnight at room temperature. The reaction progress was monitored by TLC. After the reaction was completed, acetone was added, and the mixture was stirred at room temperature for 1 h. The solvent was dried by spin drying, and the mixture was separated and purified by silica gel chromatography. After separation, an appropriate amount of MeOH was added to dissolve the product after column chromatography, and the pre-treated Na + The ion exchange resin was used for 30 minutes to obtain 6.58 g of compound Sulfavant A with a yield of 51%.

[0040] like Figure 4 , Figure 5 As shown, the structural characterization data of compound Sulfavant A: 1 H NMR(400MHz,MeOD / CDCl3)δ5.28(s,1H),4.42(t,J=12.5Hz,1H),4.31(d,J=7.6Hz,1H),4.17(dd,J=12.0,6.8Hz,1H),4.02(s,1H),3.75(d,J=5.5Hz,2H) ,3.52–3.31(m,1H),3.26(d,J=7.3Hz,2H),3.10(dd,J=7.4Hz,1H),2.30(dd, J=23.0,16.1Hz,4H),1.62(s,4H),1.27(s,58H),0.89(t,J=6.3Hz,6H);LCMS m / z849.6[M-Na] - .

[0041] The synthesis process of Sulfavant A in the present invention is also applicable to the synthesis process of one or more compounds in a class of SQDG. Specific operation steps: During the condensation reaction, stearic acid is replaced with the corresponding alkane carboxylic acid, and the other synthesis steps are consistent with or similar to the synthesis steps of synthesizing Sulfavant A, so as to synthesize one or more compounds in a class of SQDG.

[0042] The above embodiments are only used to illustrate the technical ideas and features of the present invention, and are not intended to be the only or limit the present invention. It should be understood by those skilled in the art that various changes or equivalent substitutions made to the present invention without departing from the scope of the present invention all fall within the scope of protection of the present invention.

Claims

1. A method for synthesizing a vaccine adjuvant Sulfavant A, characterized in that: The following steps are involved: The -OAc group on the anomeric carbon in compound 3 was selectively removed to obtain compound 4; compound 4 was subjected to Schmidt glycosylation reaction to obtain compound 6, and the reaction formula is as follows: Among them, THF is tetrahydrofuran; DBU is 1,8-diazabicycloundec-7-ene; DCM is dichloromethane; TFK is trifluoroacetone.

2. The method for synthesizing the vaccine adjuvant Sulfavant A according to claim 1, characterized in that: The steps for synthesizing compound 3 are as follows: the 6th hydroxyl group of D-glucose is introduced with a -Ts protecting group, the remaining hydroxyl groups are introduced with -Ac protecting groups, and the -SAc protecting group replaces the -Ts protecting group to obtain compound 3. The reaction formula is as follows: Among them, -Ts is p-toluenesulfonyl; -Ac is acetyl; -SAc is thioacetyl; Py is pyridine; TsCl is p-toluenesulfonyl chloride; DMF is dimethylformamide; Ac2O is acetic anhydride.

3. The method for synthesizing the vaccine adjuvant Sulfavant A according to claim 1, characterized in that: The steps for synthesizing compound 4 are as follows: dissolving compound 3 in tetrahydrofuran, adding benzylamine, and stirring at 10°C to 25°C overnight; after the reaction is completed, adding water to quench the reaction, extracting with ethyl acetate, and drying and concentrating the organic phase; purifying the crude product by a chromatographic column to obtain compound 4, wherein the ratio of petroleum ether to ethyl acetate in the chromatographic column is 1:

2.

4. The method for synthesizing the vaccine adjuvant Sulfavant A according to claim 3, characterized in that: In the step of synthesizing compound 4, benzylamine is replaced by hydrazine hydrate or ammonium carbonate, or by ethylenediamine and acetic acid.

5. The method for synthesizing the vaccine adjuvant Sulfavant A according to claim 3, characterized in that: In the step of synthesizing compound 4, the mixture was stirred at 20°C overnight.

6. The method for synthesizing the vaccine adjuvant Sulfavant A according to claim 1, characterized in that: The steps for synthesizing compound 6 are as follows: dissolving compound 4 in dichloromethane, adding 1,8-diazabicycloundec-7-ene, replacing the atmosphere with nitrogen three times, cooling the temperature to -40°C~-10°C, and then slowly dropping trichloroacetonitrile, maintaining -40°C~-10°C and stirring for 1h after the dropping is complete, and monitoring the reaction with a plate until compound 4 is completely consumed; then adding trifluoroacetone, acetone glycerol acetal and 4A molecular sieves, replacing the atmosphere with nitrogen three times, cooling the temperature to -40°C~-10°C, and then slowly dropping boron trifluoride etherate, maintaining -40°C~-10°C and stirring for 1h after the dropping is complete, and after the reaction is complete, adding triethylamine to quench the reaction, extracting with ethyl acetate, drying and concentrating the organic phase, and purifying the crude product by a chromatographic column to obtain compound 6, wherein the ratio of petroleum ether to ethyl acetate in the chromatographic column is 2:

1.

7. The method for synthesizing the vaccine adjuvant Sulfavant A according to claim 6, characterized in that: In the step of synthesizing compound 6, 1,8-diazabicycloundec-7-ene is replaced with potassium carbonate.

8. The method for synthesizing the vaccine adjuvant Sulfavant A according to claim 6, characterized in that: In the step of synthesizing compound 6, the temperature was -30°C.

9. The method for synthesizing the vaccine adjuvant Sulfavant A according to claim 1, characterized in that: The steps for synthesizing SulfavantA are: The acetal protecting group of compound 6 is selectively opened to obtain compound 7, the structural formula of which is as follows: ； Compound 7 is reacted with stearic acid to obtain compound 8, the structural formula of which is as follows: ； Oxidation of the -SAc protecting group of compound 8 to -SO3 - , compound 9 is obtained, the structural formula is as follows: ； The compound 9 was subjected to removal of the peracetyl protecting group, and then passed through a sodium ion exchange resin to obtain the compound Sulfavant A, the structural formula of which is as follows: 。

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