Zwitterionic polysaccharide PS A2 pentasaccharide repetitive unit compound and decane repetitive unit compound and synthesis method thereof

Abstract

The invention belongs to the technical field of polysaccharide vaccine vector synthesis, and relates to a pentasaccharide repeating unit and decasaccharide repeating unit compound of zwitterionic polysaccharide PS A2 and a synthesis method thereof. The PS A2 pentasaccharide repeating unit is successfully synthesized through a [2 + 2 + 1] strategy, and the technical problems of construction of a mannoheptaose C6-position ether bond, determination of a side chain methyl configuration, efficient construction of a 1, 2-cis-glucosidic bond, synthesis of multiple amino sugars and the like in the synthesis process are solved. The pentasaccharide repeating unit is coupled with other compounds and can be used for researching the potential anticancer effect of the PS A2. The pentasaccharide repeating units with different chiral methyl groups on the side chains provided by the invention can be used for subsequently performing activity screening on the two pentasaccharide repeating units to compare the influence of different methyl chirality on antigenicity, so that a foundation is laid for bacteroides fragilis sugar vaccines; the decasaccharide repeating unit provided by the invention provides a new path for synthesizing long-chain zwitterionic polysaccharide PS A2.

Description

Technical Field

[0001] This invention belongs to the field of polysaccharide vaccine carrier synthesis technology, and relates to a zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound and a decasaccharide repeating unit compound and their synthesis method. Background Technology

[0002] Bacteroides are a rich group of anaerobic pathogens, accounting for more than 25% of the bacteria in the human gut. While essential for the human metabolic system, they can also cause serious diseases such as sepsis and abdominal abscesses. Among Bacteroides, *Bacteroides fragilis* is the most virulent due to its virulence factors, including hemagglutinin, adhesin, polysaccharide capsules, and fimbriae. Because of the high morbidity and mortality rates of *Bacteroides fragilis* infections, this Gram-negative bacterium has been extensively studied in recent years. Research indicates its association with various human diseases, such as inflammatory bowel disease (IBD), colorectal cancer, gynecological infections, gangrenous appendicitis, brain abscess, meningitis, endocarditis, pericarditis, and bacteremia.

[0003] Vaccine development based on bacterial surface polysaccharides faces challenges. Traditional neutral or anionic polysaccharides can only trigger T cell-independent immune responses, resulting in a predominantly transient IgM response and a lack of immune memory. To address this, modern vaccines have established protein-carrier conjugation technology systems. Through chemical conjugation, polysaccharide antigens are linked to carrier proteins such as CRM197, diphtheria toxoid (DT), or tetanus toxoid (TT). This glycoprotein complex, aided by the polypeptide epitopes of the carrier protein, is presented via MHC-II molecules on antigen-presenting cells, effectively activating CD4+ T cells and establishing a Th cell-assisted immune microenvironment. This mechanism not only promotes the conversion of B cell antibody classes from IgM to IgG but also induces the formation of memory B cells, thereby establishing long-lasting immune protection. This technological breakthrough has driven the clinical translation of major products such as multivalent pneumococcal conjugate vaccines (PCV series) and meningococcal conjugate vaccines.

[0004] In studies of the immunogenicity of natural polysaccharides, zwitterionic polysaccharides (ZPS) have exhibited unique biological properties. ZPS can enter antigen-presenting cells (APCs) without protein conjugation and partially dissociate into ZPS fragments, which can be loaded onto the major histocompatibility class II (MHC-II) receptor HLADR. The antigen / MHC-II is presented to the cell surface and can bind to CD4+ T cells via the αβT cell receptor (αβTCR), generating an adaptive immune response. Activated CD4+ T cells release cytokines, which can activate cytotoxic T cells (CTLs) and B cells to produce high-affinity IgG antibodies and memory B cells required for a durable immune response. Based on these unique findings, researchers have begun to explore the potential of ZPS as a novel vaccine vector. In the field of tumor immunotherapy, ZPS glycoantigen complexes, such as Tn-PS A1, STn-PS A1, TF-PS B, and Globo H-PSA1 conjugates, constructed using precise conjugation technology, have been prepared and have elicited strong immune responses. Extensive experimental studies suggest that ZPS may be a potential alternative to carrier proteins for developing next-generation glycoconjugate vaccines.

[0005] Currently, the zwitterionic polysaccharides isolated from Bacteroides fragilis include PS A1, PS A2, and PS B, with the following structures:

[0006]

[0007] PS A1 is a polysaccharide with a tetrasaccharide repeating unit, and its synthesis has been reported by scholars. PSB is a polysaccharide with a hexasaccharide repeating unit, and its synthesis was also reported in 2024. However, there are no reports of PS A2's synthesis to date. Summary of the Invention

[0008] Therefore, the present invention aims to provide a zwitterionic polysaccharide PS A2 with a pentasaccharide repeating unit and its synthetic method, which utilizes abundant raw materials and achieves high yield. The present invention also provides a zwitterionic polysaccharide PS A2 with a decasaccharide repeating unit and its synthetic method, providing a new pathway for the synthesis of zwitterionic polysaccharide PS A2 using the decasaccharide repeating unit synthesized by this method.

[0009] To achieve the above objectives, the present invention adopts the following technical solution:

[0010] This invention provides a zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound, comprising the following structural formula:

[0011]

[0012] Because the compounds have different chiral methyl groups on their side chains, they include compounds 2-1a and 2-1b, whose structures are as follows:

[0013]

[0014] Further activity screening of these two pentasaccharide repeating units and comparison of the effects of different methyl chiralities on antigenicity can lay the foundation for sugar vaccines against Bacteroides fragilis and provide synthetic reference for the subsequent synthesis of long-chain PS A2.

[0015] This invention further provides a method for synthesizing the above-mentioned zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound, comprising the following steps:

[0016] S1, using compounds 2-7 and 2-8 in a molar ratio of 1:1.1 to 1.3 as raw materials, obtained compound 2-5 through glycosylation and deprotection reactions;

[0017] S2, using compounds 2-9 and 2-10 in a molar ratio of 1.3 to 1.5:1 as raw materials, yielded compound 2-6 through glycosylation and deprotection reactions;

[0018] S3, using compounds 2-5 and 2-6 in a molar ratio of 1.1 to 1.3:1 as raw materials, obtained compound 2-3 through glycosylation and deprotection reactions;

[0019] S4, using compounds 2-3 and 2-4 in a molar ratio of 1:1.9 to 2.2 as raw materials, glycosylation reaction yields compound 2-2;

[0020] S5, the compound 2-2 was deprotected to obtain the zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound 2-1;

[0021] PG1 through PG7 are protecting groups, each independently selected from Bn, TCA, TIPS, Ac, (CH2)5N3, Lev, or Mp, where Bn is benzyl, TCA is trichloroacetyl, TIPS is triisopropylsilyl, Ac is acetyl, Lev is levulinyl, and Mp is p-methoxyphenyl. The specific synthetic route is as follows:

[0022]

[0023] Furthermore, the present invention provides a compound 2-7 as described in S1, wherein compound 2-7 comprises 2-7a or 2-7b, and the synthesis process of 2-7a and 2-7b comprises the following steps:

[0024] S1-1, using compound 2-12 as the starting material, compounds 2-14a and 2-14b are synthesized through the following steps S1-11 and S1-12:

[0025] S1-11, the C6 position of compound 2-12 was oxidized using a two-step reaction involving Swern oxidation and Wittig oxidation to yield compound 2-13; the specific synthetic route is as follows:

[0026]

[0027] S1-12, K2OsO4·2H2O, K3Fe(CN)6, and K2CO3 were dissolved in a mixed solvent of t-BuOH and H2O with a volume ratio of 0.9–1.1:1. Compound 2-13 was then added to the mixed solvent and reacted to obtain compounds 2-14a and 2-14b. The molar ratio of K2OsO4·2H2O, K3Fe(CN)6, and K2CO3 to compound 2-13 was 1:59–61:65–67:19–21. The specific synthetic route is as follows:

[0028]

[0029] S1-2, using compound 2-14b as the starting material, compounds 2-18a and 2-18b are synthesized through the following steps S1-21, S1-22, S1-23 and S1-24:

[0030] S1-21, hydroxyl protection of C7 of compound 2-14b yields compound 2-15;

[0031] Preferably, compound 2-14b and n-Bu2SnO in a molar ratio of 1:1.2-1.4 are dissolved in Toluene, refluxed at 110-130°C for 4-6 h, cooled to 75°C, and then protected reagent I, CsF, and CH3CN are added sequentially and reacted for 2-4 h until the reaction is complete to obtain compound 2-15; the molar ratio of protected reagent I, CsF, and compound 2-14b is 1.3-1.5:1.8-2.0:1; the preferred protected reagent I is BnBr.

[0032] S1-22, esterification of the C6 hydroxyl group of compound 2-15 to obtain compound 2-16;

[0033] Preferably, DMAP-Tf, DMAP, and compound 2-24 in a molar ratio of 0.4–0.5:1:0.4–0.5 are dissolved in DCM and mixed to form a reaction solution. Then, compound 2-15 is added to the reaction solution, wherein the molar ratio of compound 2-24 to compound 2-15 is 2–2.1:1. The reaction is allowed to proceed at room temperature until complete, and the reaction is quenched with saturated NaHCO3 solution. After extraction with DCM, compound 2-16 is obtained by washing, drying, filtering, concentrating, and separating.

[0034] The synthesis of compound 2-24 is as follows: 1,3-propanediol was dissolved in DCM, and TEA and TBDPSCl were added sequentially. The reaction was allowed to proceed to completion at room temperature to obtain compound 2-23. Compound 2-23 was then dissolved in a mixed solvent of DCM and H2O at a volume ratio of 1.9–2.1:1. TEMPO and BAIB were added sequentially, and the reaction was allowed to proceed to completion overnight at room temperature. The reaction was quenched with Na2S2O3, extracted with DCM, and the product was washed, dried, filtered, concentrated, and separated to obtain compound 2-24. The molar ratio of compound 2-23 to TEMPO and BAIB was 1:0.55–0.65:1.9–2.1. The specific synthetic route is as follows:

[0035]

[0036] S1-23, under the action of CpTi(Me)2, the ester group in compound 2-16 is converted into an olefin to obtain compound 2-17;

[0037] Preferably, compound Cp2TiCl2 is dissolved in Toluene, cooled to 0°C, and CH3MgCl is added under N2 protection. The reaction is continued at 0°C until completion. The reaction is quenched by adding saturated NH4Cl solution, extracted with Toluene, dried with anhydrous Na2SO4, concentrated under reduced pressure, and then compound 2-16 is dissolved in it. The reaction is continued at 85-95°C until complete. The reaction is quenched with saturated NaHCO3 solution, and then washed, dried, filtered, concentrated, and separated to obtain compound 2-17. The molar ratio of Cp2TiCl2, CH3MgCl to compound 2-16 is 0.9-1.1:5:0.5.

[0038] S1-24, compound 2-17 is subjected to Pd(OH) )2 / C hydrogenation reduces the double bond to a methyl group, yielding compounds 2-18a and 2-18b;

[0039] Preferably, compound 2-17 is dissolved in a mixed solvent of MeOH, EA, and TEA in a volume ratio of 9–11:1:0.1, Pd(OH)₂ / C is added, hydrogen is displaced under an ice bath, and the reaction is allowed to proceed to completion at room temperature. The mixture is then filtered, evaporated to dryness, and directly added to the next step. The product obtained in the previous step is dissolved in THF, TBAF is added, and the reaction is allowed to proceed to completion at room temperature. After concentration and separation, compounds 2-18a and 2-18b are obtained. The molar ratio of compound 2-17 to TBAF is 0.9–1.1:2.5. The specific synthetic route is as follows:

[0040]

[0041] S1-3, using compound 2-18a as the starting material, compound 2-7a is synthesized through the following steps S1-31, S1-32 and S1-33:

[0042] S1-31, the carboxyl group in compound 2-18a is esterified to obtain compound 2-21;

[0043] Preferably, compound 2-18a is dissolved in a mixed solvent of DCM and H2O at a volume ratio of 3:0.9-1.1, and TEMPO and BAIB are added sequentially. The reaction is allowed to proceed overnight at room temperature until complete. The reaction is quenched with Na2S2O3, extracted with DCM, and then washed, dried, filtered, and concentrated to obtain a crude product. The crude product is dissolved in DMF, and a second protective reagent and KHCO3 are added sequentially. The reaction is allowed to proceed overnight at room temperature until complete. After extraction with EA, the product is washed, dried, filtered, concentrated, and separated to obtain compound 2-21. The molar ratio of compound 2-18a, TEMPO, BAIB, the second protective reagent, and KHCO3 is 0.9-1.1:0.6:2.6:1.5:2. The second protective reagent is preferably BnBr.

[0044] S1-32, compound 2-21 is obtained by removing the ketal from compound 2-21 to give compound 2-22;

[0045] Preferably, compound 2-21 is dissolved in 70-90% AcOH by mass and refluxed at 75-90°C to obtain compound 2-22;

[0046] S1-33, hydroxyl protection is performed at the C3 position of compound 2-22 to obtain compound 2-7a;

[0047] Preferably, compound 2-22 and n-Bu2SnO are dissolved in Toluene, refluxed at 120°C for 5–7 h, and then cooled to 70–80°C. Protecting reagent III, CsF, and CH3CN are then added sequentially, and a protecting group is selectively attached at the C3 position at 70–80°C to obtain compound 2-7a. The molar ratio of compound 2-22, n-Bu2SnO, protecting reagent III, and CsF is 0.9–1.1:1.5:1.5:3, and BnBr is preferably the protecting reagent III. The specific synthetic route is as follows:

[0048]

[0049] Alternatively, S1-3 uses compound 2-18b as a starting material to synthesize compound 2-7b via the following steps S1-31, S1-32, and S1-33:

[0050] S1-31, the carboxyl group in compound 2-18b is esterified to obtain compound 2-53;

[0051] Preferably, compound 2-18b is dissolved in a mixed solvent of DCM and H2O at a volume ratio of 3:0.9-1.1, and TEMPO and BAIB are added sequentially. The reaction is allowed to proceed overnight at room temperature until complete. The reaction is quenched with Na2S2O3, extracted with DCM, and the crude product is obtained after washing, drying, filtration, and concentration. The crude product is then dissolved in DMF, and protecting reagent II and KHCO3 are added sequentially. The reaction is allowed to proceed overnight at room temperature until complete. After extraction with EA, the product is obtained after washing, drying, filtration, concentration, and separation to obtain compound 2-53. The molar ratio of compound 2-18b, TEMPO, BAIB, protecting reagent II, and KHCO3 is 0.9-1.1:0.6:3:1.5:2. The preferred protecting reagent II is BnBr.

[0052] S1-32, compound 2-53 is obtained by removing the ketal to give compound 2-54;

[0053] Preferably, compound 2-53 is dissolved in 70-90% AcOH by mass and refluxed at 75-90°C to obtain compound 2-54;

[0054] S1-33, hydroxyl protection is performed at the C3 position of compound 2-54 to obtain compound 2-7b;

[0055] Preferably, compound 2-54 and n-Bu2SnO are dissolved in Toluene, refluxed at 110–130°C for 5–7 h, and then cooled to 70–80°C. Protecting reagent III, CsF, and CH3CN are then added sequentially, and a protecting group is selectively attached at the C3 position at 70–80°C to obtain compound 2-7b. The molar ratio of compound 2-54, n-Bu2SnO, protecting reagent III, and CsF is 0.9–1.1:1.5:1.5:2, and BnBr is preferably the protecting reagent III. The specific synthetic route is as follows:

[0056]

[0057] Furthermore, the present invention provides compounds 2-8 as described in S1, the synthesis of which includes the following steps:

[0058] S1-4, using compound 2-27 as a raw material, wherein the two hydroxyl groups on C2 and C4 of compound 2-27 are subjected to an upper protecting group, azide inversion, amino inversion and amino protection to obtain compound 2-28;

[0059] S1-5, compound 2-28 is desulfurized to obtain compound 2-29;

[0060] Preferably, compound 2-28 is dissolved in DCM, and NIS and TFA are added sequentially at 0°C. The reaction is carried out at 0°C until complete, the reaction is quenched with Na2S2O3, extracted with DCM, and then washed, dried, filtered, concentrated and separated to obtain compound 2-29. The molar ratio of compound 2-28, NIS and TFA is 0.9-1.1:2:4.

[0061] Compound 2-29 was then glycosylated with the trifluoroacetylimine ester activator PTFAI under Cs₂CO₃ conditions to obtain compound 2-8. Preferably, compound 2-29 was dissolved in Acetone, cooled to 0°C, and Cs₂CO₃ and PTFAI were added sequentially. The reaction was allowed to proceed at room temperature until complete, and the reaction was quenched with TEA. After concentration and separation, compound 2-8 was obtained. The molar ratio of compound 2-29 to Cs₂CO₃ and PTFAI was 0.9–1.1:2:1.5. The specific synthetic route is as follows:

[0062]

[0063] Furthermore, the present invention provides a compound 2-5 as described in S1, which is prepared by using compounds 2-7 and 2-8 in a molar ratio of 1.1 to 1.3:1 as raw materials, and undergoing a stereoselective glycosylation reaction in a DCM solvent system with TBSOTf as a catalyst at -40°C to obtain compound 2-48; compound 2-48 is dissolved in a mixed solvent of acetonitrile and water in a volume ratio of 4:0.9 to 1.1, and CAN is added at 0°C. After reacting at room temperature to remove the PG7 protecting group from compound 2-48, compound 2-49 is obtained. The molar ratio of compound 2-48 to CAN is 0.9–1.1:3; compound 2-49 undergoes a glycosylation reaction with PTFAI under Cs₂CO₃ conditions to obtain compound 2-5. Preferably, compound 2-49 is dissolved in Acetone, cooled to 0°C, and Cs₂CO₃ and PTFAI are added sequentially. The reaction is carried out at room temperature until complete, and the reaction is quenched by adding TEA. After concentration and separation, compound 2-5 is obtained; the molar ratio of compound 2-49 to Cs₂CO₃ and PTFAI is 0.9–1.1:2:1.5; the specific synthetic route is as follows:

[0064]

[0065] Furthermore, the present invention provides compounds 2-6 as described in S2, the synthesis of which includes the following steps:

[0066] S2-1, using compounds 2-9 and 2-10 in a molar ratio of 1.3–1.5:1 as starting materials, was synthesized by glycosylation in a DCM system under TBSOTf catalysis at -20°C to yield compound 2-50; the specific synthetic route is as follows:

[0067]

[0068] S2-2, Compound 2-50 was deprotected by the PG5 protecting group to obtain compound 2-6;

[0069] Preferably, compound 2-50 is dissolved in a mixed solvent of DCM and H2O at a volume ratio of 10:0.9-1.1. A buffer solution with pH=7 and DDQ are added sequentially at 0°C, and the reaction is allowed to proceed to completion at room temperature. The reaction is quenched with saturated Na2S2O3, extracted with DCM, and then washed, dried, filtered, concentrated, and separated to obtain compound 2-6. The molar ratio of compound 2-50 to DDQ is 1:1.9-2.1. The specific synthetic route is as follows:

[0070]

[0071] Furthermore, the present invention provides a compound 2-3 as described in S3, the synthesis of which includes the following steps:

[0072] S3-1, using compounds 2-5 and 2-6 in a molar ratio of 1.1–1.3:1 as starting materials, was synthesized by glycosylation in a DCM system under TBSOTf catalysis at -20°C to yield compound 2-51; the specific synthetic route is as follows:

[0073]

[0074] S3-2, Compound 2-51 was deprotected by the PG6 protecting group to obtain compound 2-3;

[0075] Preferably, compound 2-51 is dissolved in a mixed solution of AcOH and Py at a volume ratio of 0.9–1.1:4, 80% hydrazine hydrate is added at 0°C, and the reaction is carried out at room temperature until complete. After dilution with EA, the mixture is washed, dried, filtered, and separated to obtain compound 2-3. The specific synthetic route is as follows:

[0076]

[0077] Furthermore, the present invention provides a compound 2-2 as described in S4, the synthesis method of which is as follows: dissolving compounds 2-3 and 2-4 in DCM, and adding freshly activated... MS, cooled to -20℃, then TBSOTf was added, and the reaction was carried out at -20℃ until complete. After quenching the reaction with TEA, the mixture was separated by concentrated column chromatography to obtain compound 2-2.

[0078] Furthermore, the synthesis of compound 2-1, a zwitterionic polysaccharide PS A2 pentasaccharide repeating unit, described in S5, includes the following steps:

[0079] S5-1, using compound 2-2 as a raw material, the PG3 protecting group is removed to obtain compound 2-52;

[0080] Preferably, compound 2-2 is dissolved in a mixed solvent of THF and Py at a volume ratio of 1:0.9–1.1, cooled to 0°C, and then the HF / Py mixture is added. The reaction is carried out at 40°C until complete. After quenching the reaction with solid NaHCO3, compound 2-52 is obtained by filtration and separation. The specific synthetic route is as follows:

[0081]

[0082] S5-2, after hydrogenation and removal of protecting groups, compound 2-52 yields zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound 2-1;

[0083] Preferably, compound 2-52 is dissolved in a mixed solution of t-BuOH and H2O at a volume ratio of 6-8:3, Pd(OH)2 / C is added, hydrogen is replaced three times under an ice bath, and the reaction is carried out at room temperature for 4-6 days. The mixture is then evaporated to dryness to obtain the crude product. The crude product is dissolved in a 0.8-1.2M lithium hydroxide solution and reacted at room temperature until the reaction is complete to obtain the zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound 2-1. The specific synthetic route is as follows:

[0084]

[0085] This invention further provides a zwitterionic polysaccharide PS A2 decansaccharide repeating unit compound, comprising the following structural formula:

[0086]

[0087] Because the compounds have different chiral methyl groups on their side chains, they include compounds 3-1a and 3-1b, whose structures are as follows:

[0088]

[0089] This invention further provides a method for synthesizing the above-mentioned zwitterionic polysaccharide PS A2 decasaccharide repeating unit compound, characterized by comprising the following steps:

[0090] (1) Using compounds 3-6 and 3-5 in a molar ratio of 2–2.1:1 as starting materials, compound 3-4 was obtained by glycosylation in a DCM system under the catalysis of TBSOTf at -20°C; the specific synthetic route is as follows:

[0091]

[0092] (2) Compound 3-4 was deprotected by the PG6 protecting group to obtain compound 3-3;

[0093] Preferably, compound 3-4 is dissolved in a mixed solution of AcOH and Py at a volume ratio of 0.9–1.1:4, 80% hydrazine hydrate is added at 0°C, and the reaction is carried out at room temperature until complete. After dilution with EA, the solution is washed, dried, filtered, and separated to obtain compound 3-3. The specific synthetic route is as follows:

[0094]

[0095] (3) Using the aforementioned compound 3-3 in a molar ratio of 2.5 to 2.7:1 and a monosaccharide compound as raw materials, compound 3-2 was obtained by glycosylation in a DCM system under the catalysis of TfOH at -20°C; the specific synthetic route is as follows:

[0096]

[0097] (4) After hydrogenation and removal of the protecting group, compound 3-2 is obtained as decansaccharide repeating unit compound 3-1;

[0098] Preferably, compound 3-2 is dissolved in a mixed solvent of THF and Py in a volume ratio of 3:0.9–1.1, cooled to 0°C, and then the HF / Py mixture is added. The reaction is carried out at 40°C until complete. After quenching the reaction with solid NaHCO3, the mixture is filtered, separated, and distilled under reduced pressure to obtain compound 3-1. The specific synthetic route is as follows:

[0099]

[0100] Furthermore, the present invention provides a compound 3-6 described in step (1), the synthesis method of which is as follows:

[0101] Compound 2-51, after the PG5 protecting group is removed, yields compound 3-12. Preferably, compound 2-51 is dissolved in a mixed solvent of acetonitrile and water at a volume ratio of 4:0.9-1.1, and CAN is added at 0°C. The mixture is then heated to room temperature to remove the PG5 protecting group from compound 2-51, yielding compound 3-12. The molar ratio of compound 2-51 to CAN is 0.9-1.1:3. Compound 3-12 undergoes a glycosylation reaction with PTFAI under Cs2CO3 conditions to yield compound 3-6. Preferably, compound 3-12 is dissolved in Acetone, cooled to 0°C, and Cs2CO3 and PTFAI are added sequentially. The reaction is carried out at room temperature until complete, and the mixture is concentrated and separated to obtain compound 2-5. The molar ratio of compound 3-12 to Cs2CO3 and PTFAI is 0.9-1.1:2:1.5. The specific synthetic route is as follows:

[0102]

[0103] Furthermore, the present invention provides a compound 3-5 described in step (1). The synthesis method of this compound is as follows: compound 2-51 is dissolved in a mixed solvent of THF and Py with a volume ratio of 1:0.9-1.1, cooled to 0°C, and then an HF / Py mixture is added. The reaction is carried out at 35-45°C until the reaction is complete. After adding NaHCO3 solid to quench the reaction, the mixture is filtered and separated to obtain compound 3-5. The specific synthesis route is as follows:

[0104]

[0105] The beneficial effects of this invention are as follows: This invention successfully synthesized the pentasaccharide repeating unit of PS A2 using a [2+2+1] strategy, overcoming technical difficulties such as the construction of the C6 ether bond of mannohepose and the determination of the side chain methyl configuration, efficient construction of 1,2-cis-glycosidic bonds, and the synthesis of multiple amino sugars during the synthesis process. The pentasaccharide repeating unit provided by this invention can be coupled with other compounds to study the potential anticancer effects of PS A2. The pentasaccharide repeating units with different chiral methyl groups on the side chain provided by this invention allow for subsequent activity screening of these two types of pentasaccharide repeating units, comparing the effect of different methyl chirality on antigenicity, laying the foundation for sugar vaccines against Bacteroides fragilis, and also providing a synthetic reference for the subsequent synthesis of long-chain PS A2. This invention also provides a method for synthesizing a decasaccharide repeating unit, which provides a new route for the synthesis of zwitterionic polysaccharide PS A2. Attached Figure Description

[0106] To more clearly illustrate the technical solution of the present invention, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0107] Appendix Figure 1 Compound 2-1, a pentasaccharide repeating unit of the zwitterionic polysaccharide PS A2. 1 H NMR spectrum;

[0108] Appendix Figure 2 Compound 2-1, a pentasaccharide repeating unit of the zwitterionic polysaccharide PS A2. 13 C NMR spectrum;

[0109] Appendix Figure 3 Compound 3-1 is a zwitterionic polysaccharide PS A2 decansaccharide repeating unit. 1 H NMR spectrum;

[0110] Appendix Figure 4 Compound 3-1 is a zwitterionic polysaccharide PS A2 decansaccharide repeating unit. 13 C10 NMR spectrum. Detailed Implementation

[0111] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. All mentioned embodiments are implemented based on the technical solutions of the present invention, and detailed implementation processes are given. However, it should be stated that the scope of protection of the present invention is not limited to the following embodiments.

[0112] The following embodiments provide detailed implementation procedures for the technical solutions of the present invention. Unless otherwise specified, the experimental methods used in the following experimental examples are conventional methods; unless otherwise specified, the materials and reagents used are commercially available.

[0113] Example 1: Synthesis of zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound

[0114] The zwitterionic polysaccharide PS A2 is a polysaccharide with a pentasaccharide repeating unit structure, the structure of which is as follows:

[0115] The compound is [→3)-α-D-AATp-(1→2)-α-D-HeppNAc-(1→3)-α-D-ManpNAc-(1→4)[α-L-Fucp-(1→2)]-β-D-ADGp-(1→], which contains multiple rare sugars, 1,2-cis-glycosidic bonds, and complex functional groups such as amino, acetamide, and carboxyl groups. This invention employs a [2+2+1] convergent synthetic strategy to construct the PS A2 pentasaccharide repeating unit.

[0116] The synthetic route for compound 2-1, the pentasaccharide repeating unit of the zwitterionic polysaccharide PS A2, in this embodiment is as follows:

[0117] The PS A2 pentasaccharide repeating unit consists of five monosaccharide molecules and 3-hydroxybutyric acid. The five monosaccharides are AAT, mannohepose, 2-acetaminomannose, triacetaminoglucosamine, and fucose. Compound 2-1 can be obtained from 2-2 via desilication, hydrogenation, and deacetylation. Pentasaccharide 2-2 was synthesized using a [2+2+1] convergent synthesis strategy: the all-benzyl trifluoroacetylimine donor 2-4 underwent glycosylation with the tetrasaccharide acceptor 2-3, and the α-configuration pentasaccharide product 2-2 was successfully obtained by adding diethyl ether. Tetrasaccharide 2-3 is obtained by glycosylation of disaccharide trifluoroacetylimine donor 2-5 and disaccharide acceptor 2-6. Disaccharide donor 2-5 is obtained by de-Mp-linking after glycosylation of trifluoroacetylimine donor 2-8 and monosaccharide acceptor 2-7. Disaccharide 2-6 is obtained by de-Nap after glycosylation of trifluoroacetylimine donor 2-9 and monosaccharide acceptor 2-10.

[0118] Since PS A2 contains five different monosaccharide building blocks, including 1,2-trans-α and 1,2-cis-β glycosidic bonds, the construction of the 1,2-cis-α glycosidic bond is very challenging. When constructing the glycosidic bonds of compounds 2-5, since the trifluoroacetylimine donors 2-8 do not have neighboring groups, a TIPS is selectively installed at the C3 position of 2-8. The stereoselectivity of the glycosidic bond is controlled by the TIPS. In the synthesis of the pentasaccharide 2-2, this invention provides a method of selectively adding diethyl ether to control the stereoselectivity.

[0119] I. Synthesize compounds 2-7 (including 2-7a and 2-7b) according to the following synthetic route.

[0120] Synthetic compound 2-11

[0121]

[0122] The synthesis of compound 2-11 was performed using the method described in the literature: Emmadi, M.; Kulkarni, SS Nat. Prod. Rep. 2014, 31, 870-879.

[0123] Synthetic compound 2-12

[0124]

[0125] Compound 2-11 (16.10 g, 36.4 mmol) was dissolved in (CH3)2C(OCH3)2, and CSA (1.70 g, 7.3 mmol, 0.2 eq) was added. The reaction was carried out at room temperature for 4 h, and the reaction was confirmed to be complete by TLC. The reaction was quenched by adding TEA, and the pH was adjusted to neutral. The crude product was obtained by concentration under reduced pressure. The crude product was dissolved in 150 mL of DMF and cooled to 0 °C in an ice bath. BnBr (6.48 mL, 54.6 mmol, 1.5 eq) was added, followed by the slow addition of NaH (2.91 g, 72.8 mmol, 2 eq) in portions. The reaction was carried out at 0 °C for 6 h, and the reaction was confirmed to be complete by TLC. The reaction solution was poured into ice water in portions to quench the unreacted NaH, and the mixture was extracted with a large amount of EA. The organic phase was washed successively with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, and evaporated to dryness to obtain the crude product. The crude product was dissolved in 200 mL of THF, and TBAF (23.79 g, 91.0 mmol, 2.5 eq) was added. The mixture was reacted at room temperature for 4 h. The reaction was confirmed to be complete by TLC. The reaction solution was evaporated to dryness and separated by column chromatography (PE / EA = 7:1) to give a white solid 2-12 (10.3 g, 24.8 mmol, 68%). [α] D 25 = +85.8(c1.0,CHCl3). 11H NMR (600 MHz, CDCl3) δ 7.36 - 7.27 (m, 1H), 6.98 - 6.72 (m, 1H), 5.67 (s, 1H), 4.92 (d, J = 11.5 Hz, 1H), 4.66 (d, J = 11.5 Hz, 1H), 4.49 (t, 1H), 4.37 (d, J = 5.7 Hz, 1H), 3.85 - 3.75 (m, 1H), 3.71 (dd, J = 11.7, 4.3 Hz, 1H), 3.63 (dd, J = 9.9, 7.1 Hz, 1H), 1.53 (s, 1H), 1.42 (s, 1H). 13 13C NMR (100 MHz, CDCl3) δ 155.2, 149.8, 138.1, 128.4, 128.1, 127.8, 117.9, 114.7, 109.7, 96.3, 78.7, 75.8, 75.6, 73.0, 69.4, 62.2, 55.6, 28.0, 26.4. HRMS (ESI) Calculated for C 24 H 24 O6Na [M + Na] + 439.1727, found 439.1725.3.

[0126] Synthesis of Compound 2-13

[0127]

[0128] (COCl)₂ (6.10 mL, 72.0 mmol, 3 eq) was dissolved in 30 mL of dry DCM and cooled to -78 °C. DMSO (6.82 mL, 96 mmol, 96 mmol) was dissolved in 35 mL of dry DCM and slowly added dropwise to the (COCl)₂ solution. The reaction was stirred at -78 °C for 0.5 h. Then, compound 2-12 (10.0 g, 24.0 mmol) was dissolved in 100 mL of dry DCM and slowly added dropwise to the reaction solution. After reacting at -78 °C for 1 h, TEA (16.67 mL, 120.0 mmol, 5 eq) was added to the reaction solution, the refrigeration was turned off, and the reaction was allowed to proceed for 20 min. TLC was used to confirm the complete reaction of the starting material. The reaction solution was quenched in water, extracted with DCM, washed with water and saturated NaCl, dried over anhydrous Na₂SO₄, filtered, and evaporated to dryness to obtain a colorless crude liquid. This crude product was then directly added to the next step after being dried by an oil pump. Ph3PCH3Br (31.22 g, 96.0 mmol, 4 eq) was dissolved in 60 mL of dry THF and cooled to 0 °C. n-BuLi was slowly added dropwise to the Ph3PCH3Br solution. After reacting at 0 °C for 1 h, the temperature was lowered to -78 °C. 40 mL of the crude product solution was slowly added to the reaction system. The refrigeration was turned off, and the reaction was allowed to proceed for 12 h. TCL analysis indicated complete reaction of the starting material. The reaction was quenched with saturated NH4Cl solution, extracted with EA, and the organic phase was washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and separated by column chromatography (PE / EA = 15:1) to obtain compound 2-13 (6.15 g, 14.9 mmol, 62%). [α] D 25 = +85.8 (c 1.0, CHCl3). 1 HNMR(400MHz, CDCl3)δ7.39-7.21(m,5H),7.02-6.93(m,2H),6.84-6.76(m,2H),6.02-5.8 9(m,1H),5.64(s,1H),5.35(dt,J=17.3,1.5Hz,1H),5.20(dt,J=10.7,1.4Hz,1H),4.87(d, J=11.6Hz,1H),4.64(d,J=11.6Hz,1H),4.51-4.41(m,1H),4.37(d,J=5.7Hz,1H),4.22(dd ,J=10.0,5.6Hz,1H),3.74(s,3H),3.38(dd,J=10.1,7.0Hz,1H),1.51(s,3H),1.41(s,3H). 13C NMR (100MHz, CDCl3) δ155.1,150.2,138.2,134.7,128.3,128.0,127.7,118.0,117.5,11 4.6,109.6,96.5,79.5,78.7,75.9,73.1,69.6,55.6,28.0,26.5.HRMS(ESI)Calculated for C 24 H 24 O6Na[M+Na] + 435.1778, found 435.1779.

[0129] Synthesize compounds 2-14a and 2-14b

[0130]

[0131] K₂O₅O₂·2H₂O (274.4 mg, 0.75 mmol, 0.05 eq), K₃Fe(CN)₆ (14.72 g, 44.7 mmol, 3 eq), and K₂CO₃ (6.8 g, 49.2 mmol, 3.3 eq) were dissolved in a mixed solvent of 75 mL t-BuOH and 75 mL H₂O. The mixture was cooled to 0 °C, and compound 2-13 (6.15 g, 14.9 mmol) was added to the reaction system. The reaction was carried out at 0 °C for 24 h, and TLC was used to confirm the completeness of the reaction. The mixture was extracted with EA, washed with water and saturated NaCl, dried over anhydrous Na₂SO₄, filtered, concentrated under reduced pressure, and separated by column chromatography (PE / EA = 4:1) to obtain white solid 2-14a (2.41 g, 5.4 mmol, 36%) and white solid 2-14b (2.63 g, 5.9 mmol, 40%). Compound 2-14a: 1 H NMR (400MHz, CDCl3) δ7.39-7.28 (m, 5H), 6.93 (d, 2H), 6.84 (d, J = 9.1Hz, 2H), 5.77 (s ,1H),4.94(d,J=11.3Hz,1H),4.68(d,J=11.2Hz,1H),4.50(t,J=6.3Hz,1H),4.37(d, J=5.7Hz,1H),3.93(t,J=5.0Hz,1H),3.83-3.78(m,1H),3.77(s,3H),3.71(dd,1H),3 .44(dd,J=11.5,6.2Hz,1H),3.35(dd,J=11.5,4.8Hz,1H),1.56(s,3H),1.42(s,3H). 13C NMR (100MHz, CDCl3) δ155.2,148.6,138.0,128.4,128.2,127.9,117.3,114.8, 109.8,95.5,78.7,75.4,74.9,73.3,69.7,68.9,64.5,55.6,28.0,26.4.2-14b: 1 H NMR (400MHz, CDCl3) δ7.41-7.28(m,5H),6.97(d,J=9.1Hz,2H),6.83(d,J=9.0H z,2H),5.66(s,1H),5.00(d,J=11.4Hz,1H),4.66(d,J=11.4Hz,1H),4.51(t,J=6 .2Hz,1H),4.38(d,J=5.8Hz,1H),3.83(dd,J=10.2,5.3Hz,1H),3.78(d,J=8.3Hz ,4H),3.69(dd,J=9.3,6.8Hz,1H),3.56-3.41(m,2H),1.56(s,3H),1.43(s,3H). 13 C NMR (100MHz, CDCl3) δ155.2,149.4,137.1,128.6,128.3,128.2,117.6,114.8,109.9,96.0,78. 6,78.5,77.4,77.0,76.7,75.6,73.1,72.8,68.3,63.1,55.6,28.0,26.3.HRMS(ESI)Calculated for C 24 H 30 O8Na[M+Na] + 469.1833, found 469.1831.

[0132] Synthesis of compound 2-15

[0133]

[0134] Compound 2-14b (2.63 g, 5.9 mmol) and n-Bu2SnO (2.02 g, 8 mmol, 1.5 eq) were dissolved in 25 mL of dry Toluene and refluxed at 120 °C for 5 h. The mixture was then cooled to 75 °C, and BnBr (0.96 mL, 8.1 mmol, 1.5 eq), CsF (1.64 g, 10.8 mmol, 2 eq), and 25 mL of dry CH3CN were added sequentially. The reaction was carried out at 75 °C for 3 h. The reaction was confirmed to be complete by TLC. The mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (PE / EA = 6:1) to give a white solid 2-15 (2.38 g, 4.4 mmol, 82%). [α]D25 = +89.4 (c 1.0, CHCl3). 1 H NMR (400MHz, CDCl3) δ7.38-7.19(m,10H),6.95(d,J=9.0Hz,1H),6.78(d,J=9. 0Hz,1H),5.64(s,1H),4.93(d,J=11.3Hz,1H),4.61(d,J=11.3Hz,1H),4.49(t, J=6.2Hz,1H),4.41-4.26(m,3H),4.06-3.97(m,1H),3.85-3.71(m,5H),3.47(d d,J=10.0,3.2Hz,1H),3.38(dd,J=10.0,6.8Hz,1H),1.54(s,3H),1.41(s,3H). 13 C NMR (100MHz, CDCl3) δ155.1,149.8,138.2,137.6,128.5,128.3,128.2,127.9,127.7,127.5,117.6,114 .7,109.7,96.0,78.7,77.5,75.6,73.3,72.8,72.2,70.9,68.6,55.6,27.9,26.3.HRMS(ESI)Calculated for C 31 H 36 O8Na[M+Na]+559.2302, found 559.2291.

[0135] Synthetic compound 2-16

[0136] Synthetic compound 2-24

[0137]

[0138] 1,3-Propanediol (5.50 mL, 76.0 mmol, 3 eq) was dissolved in 50 mL of DCM, followed by the addition of TEA (5.20 mL, 38.0 mmol, 1.5 eq) and TBDPSCl (6.60 mL, 25.5 mmol). The reaction was allowed to proceed at room temperature for 8 h, and TLC analysis confirmed complete reaction. The solution was concentrated under reduced pressure and separated by column chromatography (PE / EA = 8:1) to give a white solid 2-23 (7.38 g, 23.5 mmol, 92%). [α] D 25 = -9.4(c1.0, CHCl3). 1 H NMR (400MHz, CDCl3) δ7.74-7.62(m,4H),7.48-7.33(m,6H),3.83(dt,J=8.2,5.7Hz,4H),2.48(s,1H),1.79(p,J=5.7Hz,2H),1.06(s,9H). 13 C NMR(100MHz, CDCl3)δ135.6,133.4,129.8,127.8,63.1,61.7,34.4,26.9,19.2.HRMS(ESI)Calculated forC 19 H 27 OSi[M+H] + 315.1775, found 315.1775.

[0139] Compound 2-23 (7.38 g, 23.5 mmol) was dissolved in a mixed solvent of 80 mL DCM and 40 mL H2O. TEMPO (2.20 g, 14.1 mmol, 0.6 eq) and BAIB (15.13 g, 46.9 mmol, 2 eq) were added sequentially. The reaction was allowed to proceed overnight at room temperature. TLC analysis confirmed complete reaction. The reaction was quenched with Na2S2O3, extracted with DCM, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and separated by column chromatography (PE / EA = 5:1) to give a white solid 2-24 (6.33 g, 19.3 mmol, 82%). [α] D 25 = -14.0 (c 1.0, CHCl3). 1 H NMR (400MHz, CDCl3) δ7.76-7.54(m,4H),7.48-7.32(m,6H),3.95(t,J=6.2Hz,2H),2.60(t,J=6.2Hz,2H),1.04(s,9H). 13C NMR(100MHz, CDCl3)δ177.3,135.6,133.3,129.8,127.8,59.7,37.5,26.74,19.2.HRMS(ESI)Calculated forC 19 H 25 O3Si[M+H] + 329.1568, found 329.1570.

[0140] Synthetic compound 2-16

[0141]

[0142] DMAP-Tf (3.56 g, 8.8 mmol, 2 eq), DMAP (2.39 g, 19.6 mmol, 4.5 eq), and 2-24 (2.89 g, 8.8 mmol, 2 eq) were dissolved sequentially in 23 mL of DCM and stirred for 2 min. Then, 2-15 (2.38 g, 4.4 mmol) was added to the reaction solution, and the reaction was allowed to proceed at room temperature for 8 min. The reaction was confirmed to be complete by TLC. The reaction was quenched with saturated NaHCO3 solution, extracted with DCM, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and separated by column chromatography (PE / EA = 15:1) to obtain a colorless liquid 2-16 (3.54 g, 4.2 mmol, 95%). [α] D 25 = +58.3 (c 1.0, CHCl3). 1 H NMR (400MHz, CDCl3) δ7.67-7.60(m,4H),7.43-7.27(m,10H),7.27-7.15(m,6H),7.01-6.94(m,2H),6.78-6.71(m,2H ),5.61(s,1H),5.52-5.45(m,1H),4.87(d,J=11.5Hz,1H),4.56(d,J=11.5Hz,1H),4.44(t,J=6.2Hz,1H),4.39(s,2H ),4.32(d,J=6.1Hz,1H),4.00(dd,J=10.3,2.2Hz,1H),3.82-3.75(m,2H),3.73-3.70(m,1H),3.70-3.67(m,1H),3.6 6(s,3H),3.57(dd,J=10.3,6.7Hz,1H),2.42-2.29(m,1H),2.29-2.19(m,1H),1.47(s,3H),1.39(s,3H),1.00(s,9H). 13CNMR(100MHz,CDCl3)δ170.5,155.0,149.9,138.13,138.08,135.57,135.5 5,133.6,133.5,129.7,128.29,128.27,128.0,127.72,127.69,127.6,127. 54,127.50,117.9,114.5,109.7,96.2,79.1,75.7,75.6,72.9,72.5,71.0, 68.9,67.7,59.6,55.6,37.6,27.9,26.8,26.4,19.1.HRMS(ESI)Calculated for C 50 H 59 O 10 Si[M+H] + 869.36914, found 869.369.

[0143] Synthetic compound 2-17

[0144]

[0145] Compound Cp2TiCl2 (2.10 g, 8.4 mmol, 2 eq) was dissolved in 20 mL of dry Toluene, cooled to 0 °C, and 2.5 M CH3MgCl (16.8 mL, 42.0 mmol, 10 eq) was slowly added dropwise under N2 protection. The reaction was carried out at 0 °C for 1 h, and the reaction was quenched with saturated NH4Cl solution. The mixture was extracted with Toluene, dried over anhydrous Na2SO4, and concentrated under reduced pressure to about 10 mL. Compound 2-16 (3.54 g, 4.2 mmol) was dissolved in 10 mL of dry Toluene and reacted at 90 °C for 4 h. The reaction was confirmed to be complete by TLC. The reaction was quenched with saturated NaHCO3 solution, extracted with EA, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and separated by column chromatography (PE / EA = 20:1) to give a colorless liquid 2-17 (2.87 g, 3.4 mmol, 80%). [α] D 25 = +33.1(c1.0,CHCl3). 1H NMR (400MHz, CDCl3) δ7.43-7.19(m,10H),7.08-6.95(m,2H),6.88-6.71(m,2H),5.53(s,1H),4 .86(d,J=11.4Hz,1H),4.58(d,J=11.4Hz,1H),4.48(d,J=11.9Hz,1H),4.44(t,J=6.1Hz,1H),4. 37(d,J=11.9Hz,1H),4.31(d,J=5.8Hz,1H),3.92-3.78(m,4H),3.76(s,3H),3.68-3.55(m,3H) ,3.44(dd,J=10.2,3.1Hz,1H),1.75-1.64(m,1H),1.49(s,3H),1.40(s,3H),1.12-0.96(m,4H). 13 C NMR (100MHz, CDCl3) δ155.1,150.3,138.1,137.7,134.8,129.7,128.4,128.3,128.1,127.9,127.7,127.7,127.7,118.3,114.6,10 9.6,96.7,79.0,77.3,75.54,75.5,75.4,73.4,72.6,71.2,70.4,60.00,55.7,39.1,27.9,26.6,26.4,20.9.HRMS(ESI)Calculated for C 51 H 60 O9SiNa[M+Na] + 867.3899, found 867.3897.

[0146] Synthesize compounds 2-18a and 2-18b

[0147]

[0148] Compound 2-17 (2.87 g, 3.4 mmol) was dissolved in a mixed solvent of 27 mL MeOH, 2.7 mL EA, and 0.27 mL TEA. 1.4 g of Pd(OH)₂ / C was added, and the mixture was reacted with hydrogen in an ice bath at room temperature for 48 h. The reaction was confirmed to be complete by TLC. The product was filtered, evaporated to dryness, and directly added to the next step. The product obtained in the previous step was dissolved in 20 mL THF, and TBAF (2.22 g, 8.5 mmol, 2.5 eq) was added. The reaction was confirmed to be complete by TLC at room temperature for 4 h. After concentration under reduced pressure, the product was separated by column chromatography (PE / EA = 5:1) to give colorless oily liquids 2-18a (447.3 mg, 0.79 mmol, 23%) and 2-18b (1.1 g, 1.8 mmol, 53%). Compound 2-18a: [α] D 25 = +57.3 (c 1.0, CHCl3). 1 H NMR (400MHz, CDCl3) δ7.34-7.25(m,10H),7.06-6.95(m,2H),6.85-6.75(m,2H),5.53(s,1H),4.8 6(d,J=11.4Hz,1H),4.58(d,J=11.4Hz,1H),4.48(d,J=11.9Hz,1H),4.44(t,J=6.1Hz,1H),4.37(d ,J=11.9Hz,1H),4.31(d,J=5.8Hz,1H),3.93-3.78(m,4H),3.76(s,3H),3.67-3.56(m,3H),3.44( dd,J=10.2,3.1Hz,1H),1.77-1.63(m,1H),1.58-1.50(m,1H),1.49(s,3H),1.07(d,J=0.8Hz,3H). 13 C NMR (100MHz, CDCl3) δ155.1,150.3,138.1,137.7,134.8,129.7,128.4,128.3,128.1,127.9,127.7,127.7,127.7,118.3,114. 6,109.6,96.7,79.0,77.3,75.5,75.5,75.4,73.4,72.6,71.2,70.4,60.0,55.7,39.1,27.9,26.4,20.9.HRMS(ESI)Calculated for C 35 H 44 O9Na[M+Na] + 631.28775, found 631.28737. Compound 2-18b: [α] D25 = +66.5 (c 1.0, CHCl3). 1 H NMR (400MHz, CDCl3) δ7.41-7.14(m,10H),7.03-6.94(m,2H),6.90-6.77(m,2H),5.63(s,1H),5.00-4 .81(m,1H),4.58(d,J=11.3Hz,1H),4.49-4.26(m,4H),3.94(d,J=10.3Hz,1H),3.90-3.83(m,2H),3.8 2-3.78(m,1H),3.77(d,J=4.3Hz,3H),3.73-3.65(m,1H),3.59(dd,J=10.3,4.8Hz,1H),3.55-3.44(m, 2H),1.73-1.61(m,1H),1.58-1.47(m,4H),1.40(s,3H),1.17(d,J=6.1Hz,3H).HRMS(ESI)Calculated for C 35 H 44 O9Na[M+Na] + 631.2878, found 631.2872.

[0149] Synthetic compound 2-21

[0150]

[0151] Compound 2-18a (1.10 g, 1.8 mmol) was dissolved in a mixed solvent of 13.5 mL DCM and 4.5 mL H2O. TEMPO (171.9 mg, 1.1 mmol, 0.6 eq) and BAIB (1.55 g, 4.8 mmol, 3 eq) were added sequentially. The reaction was allowed to proceed overnight at room temperature. The reaction was confirmed to be complete by TLC. The reaction was quenched with Na2S2O3, extracted with DCM, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was dissolved in 1 mL of DMF, and BnBr (0.32 mL, 2.7 mmol, 1.5 eq) and KHCO3 (360.4 mg, 3.6 mmol, 2 eq) were added sequentially. The reaction was carried out at room temperature for 8 h. The reaction was confirmed to be complete by TLC. The product was extracted with EA, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and separated by column chromatography (PE / EA = 10:1) to give a colorless liquid 2-21 (998.0 mg, 1.4 mmol, 74%). [α] D 25 = +63.1(c 1.0, CHCl3). 1H NMR (400MHz, CDCl3) δ7.36-7.17(m,15H),7.08-6.96(m,2H),6.84-6.71(m,2H),5.54(s,1H),5.06(t,J=12.8Hz,2H),4.8 5(d,J=11.4Hz,1H),4.57(d,J=11.4Hz,1H),4.44(t,J=6.2Hz,1H),4.37(dd,J=26.0,12.0Hz,2H),4.31(d,J=5.8Hz,1H), 4.08(h,J=6.3Hz,1H),3.95-3.87(m,2H),3.79-3.74(m,1H),3.73(s,3H),3.56(dd,J=10.1,5.3Hz,1H),3.49(dd,J=10.1 ,6.7Hz,1H),2.68(dd,J=15.1,6.6Hz,1H),2.36(dt,J=17.0,8.5Hz,1H),1.48(s,3H),1.39(s,3H),1.09(d,J=6.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ171.3,155.1,150.4,138.5,138.4,136.0,128.5,128.3,128.25,128.16,128.0,127.54,127.51,127.4,118. 4,114.6,109.5,96.8,79.2,77.3,75.61,75.60,73.2,72.7,70.6,70.1,66.1,55.6,42.3,27.9,26.5,20.7.HRMS(ESI)Calculated for C 42 H 48 O 10 Na[M+Na] + 735.3140, found 735.3141.

[0152] Synthetic compound 2-22

[0153]

[0154] Compound 2-21 (998.0 mg, 1.4 mmol) was dissolved in 10 mL of AcOH (80%) and refluxed at 80 °C for 4.5 h. The reaction was confirmed to be complete by TLC. After concentration under reduced pressure, the product was separated by column chromatography (PE / EA = 2:1) to give 2-22 (791.1 mg, 1.2 mmol, 84%). [α] D 25 = +52.6 (c 1.0, CHCl3).1 H NMR (400MHz, CDCl3) δ7.50-7.10(m,15H),6.99-6.83(m,2H),6.82-6.72(m,2H),5.41(d,J=1.5Hz,1H) ,5.15(q,J=12.4Hz,2H),4.80(d,J=11.0Hz,1H),4.50(d,J=11.0Hz,1H),4.41-4.33(m,2H),4.29(dd,J =8.4,6.2,4.0Hz,1H),4.11(dd,J=8.8,3.2Hz,1H),3.98(s,1H),3.88-3.80(m,2H),3.80-3.69(m,4H) ,3.54-3.41(m,3H),2.60(dd,J=15.6,8.5Hz,1H),2.51(dd,J=15.6,3.9Hz,1H),1.23(d,J=6.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ172.7,155.1,150.2,138.4,138.3,135.7,128.7,128.41,128.38,128.29,128.25,128.0,127.6,127. 5,118.0,114.64,99.0,78.4,75.8,74.6,73.2,73.0,72.5,72.3,72.0,71.3,66.7,55.6,42.3,20.2.HRMS(ESI)Calculated forC 39 H 44 O 10 Na[M+Na] + 695.2827, found 695.2827.

[0155] Synthesize compound 2-7a

[0156]

[0157] Compound 2-22 (791.1 mg, 1.2 mmol) and n-Bu2SnO (448.1 mg, 1.8 mmol, 1.5 eq) were dissolved in 4 mL of dry Toluene and refluxed at 120 °C for 5 h. The mixture was then cooled to 75 °C, and BnBr (0.21 mL, 1.8 mmol, 1.5 eq), CsF (546.8 g, 3.6 mmol, 2 eq), and 4 mL of dry CH3CN were added sequentially. The reaction was carried out at 75 °C for 3 h, and TLC analysis showed complete reaction. The solution was concentrated under reduced pressure and separated by column chromatography (PE / EA = 3:1) to give 2-7a (762.9 mg, 1.0 mmol, 86%). [α]D 25 = +82.6 (c 1.0, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 7.34 - 7.16 (m, 15H), 7.01 - 6.93 (m, 2H), 6.81 - 6.73 (m, 2H), 5.32 (d, J = 1.5 Hz, 1H), 5.05 (s, 2H), 4.74 (d, J = 11.4 Hz, 1H), 4.66 (d, J = 11.4 Hz, 1H), 4.39 (q, J = 11.8 Hz, 2H), 4.13 - 4.04 (m, 2H), 4.01 (s, 1H), 3.91 (dd, J = 15.1, 8.2 Hz, 2H), 3.82 (t, J = 9.3 Hz, 1H), 3.71 (s, 3H), 3.65 (dd, J = 10.0, 5.9 Hz, 1H), 3.60 - 3.47 (m, 1H), 2.66 (dd, 1H), 2.41 (dd, J = 15.2, 6.0 Hz, 1H), 1.11 (d, J = 6.2 Hz, 3H). 13 1C NMR (100 MHz, CDCl3) δ 171.4, 155.1, 150.4, 138.5, 138.3, 136.0, 128.6, 128.6, 128.4, 128.3, 128.0, 127.9, 127.7, 127.6, 118.4, 114.6, 98.9, 77.5, 77.1, 76.8, 76.1, 74.5, 73.3, 72.4, 72.4, 72.1, 71.0, 70.5, 66.3, 55.7, 42.3, 20.6. HRMS (ESI) Calculated for C 46 H 50 O 10 [M + Na] + 785.3296, found 785.3306.

[0158] Synthesis of Compound 2 - 53

[0159]

[0160] Compound 2-18b (500.0 mg, 0.82 mmol) was dissolved in a mixed solvent of 7.5 mL DCM and 2.5 mL H2O. TEMPO (76.9 mg, 0.49 mmol, 0.6 eq) and BAIB (793.8 mg, 2.46 mmol, 3 eq) were added sequentially. The reaction was allowed to proceed overnight at room temperature. The reaction was confirmed to be complete by TLC. The reaction was quenched with Na2S2O3, extracted with DCM, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was dissolved in 1 mL of DMF, and BnBr (0.15 mL, 1.23 mmol, 1.5 eq) and KHCO3 (164.2 mg, 1.6 mmol, 2 eq) were added sequentially. The mixture was reacted at room temperature for 8 h. The reaction was confirmed to be complete by TLC. The product was extracted with EA, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and separated by column chromatography (PE / EA = 10:1) to obtain a colorless liquid 2-53 (434.8 mg, 0.61 mmol, 74%). 1 H NMR (400MHz, CDCl3) δ7.36-7.19(m,15H),7.06-6.94(m,2H),6.80-6.60(m,2H),5.52(s,1H) ),5.01(q,J=12.3Hz,2H),4.86(d,J=11.4Hz,1H),4.58(d,J=11.4Hz,1H),4.46-4.35(m,3H) ,4.30(d,1H),4.11-4.01(m,1H),3.96-3.86(m,2H),3.79-3.69(m,4H),3.61-3.48(m,2H), 2.53(dd,J=15.2,5.7Hz,1H),2.30(d,1H),1.50(s,3H),1.39(s,3H),1.19(d,J=6.1Hz,3H).

[0161] Synthetic compound 2-54

[0162]

[0163] Compound 2-53 (434.8 mg, 0.61 mmol) was dissolved in 5 mL of AcOH (80%) and refluxed at 80 °C for 4.5 h. The reaction was confirmed to be complete by TLC. After concentration under reduced pressure, the product was separated by column chromatography (PE / EA = 2:1) to obtain 2-54 (334.7 mg, 0.51 mmol, 84%). 1HNMR (400MHz, CDCl3) δ7.52-7.13(m,15H),7.06-6.86(m,2H),6.85-6.69(m,2H),5.41(d,J=1 .5Hz,1H),5.15(q,J=12.4Hz,2H),4.80(d,J=11.0Hz,1H),4.50(d,J=11.0Hz,1H),4.42-4.33 (m,2H),4.33-4.23(m,1H),4.11(dd,J=8.8,3.2Hz,1H),3.98(s,1H),3.88-3.79(m,2H),3.79 -3.70(m,4H),3.58-3.29(m,3H),2.55(ddd,J=19.6,15.6,6.2Hz,2H),1.24(t,J=7.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ172.7,155.1,150.2,138.4,138.3,135.7,128.6,128.41,128.38,128.29,128.25,128.0, 127.6,127.5,118.0,114.6,99.0,78.4,75.8,74.6,73.1,73.0,72.5,72.3,72.0,71.3,66.7,55.6,42.3,20.2.

[0164] Synthetic compound 2-7b

[0165]

[0166] Compounds 2-54 (334.7 mg, 0.51 mmol) and n-Bu2SnO (191.6 mg, 0.77 mmol, 1.5 eq) were dissolved in 4 mL of dry Toluene and refluxed at 120 °C for 5 h. The mixture was then cooled to 75 °C, and BnBr (90.7 μL, 0.77 mmol, 1.5 eq), CsF (154.9 mg, 1.02 mmol, 2 eq), and 4 mL of dry CH3CN were added sequentially. The reaction was carried out at 75 °C for 3 h, and TLC analysis confirmed complete reaction. The solution was concentrated under reduced pressure and separated by column chromatography (PE / EA = 3:1) to give 2-7b (762.9 mg, 1.0 mmol, 86%). 1H NMR (400MHz, CDCl3) δ7.43-7.16(m,20H),7.01-6.91(m,2H),6.85-6.70(m,2H),5.42(d,J=1.3Hz,1H),5.12(q,J=1 2.4Hz,2H),4.82(dd,J=13.1,11.3Hz,2H),4.68(d,J=11.3Hz,1H),4.55(d,J=10.9Hz,1H),4.39(q,2H),4.28-4.21 (m,1H),4.19(s,1H),4.07(dd,J=8.9,3.3Hz,1H),3.97(t,1H),3.91(d,J=9.9Hz,1H),3.86(dd,J=7.0,5.1Hz,1H), 3.73(s,3H),3.58-3.44(m,2H),2.59(dd,J=15.2,7.7Hz,1H),2.45(dd,J=15.2,5.1Hz,1H),1.21(d,J=6.1Hz,3H). 13 C NMR (100MHz, CDCl3) δ172.2,155.1,150.3,138.5,138.4,138.2,135.8,128.52,128.48,128.29,128.27,128.2,128.00,127.8,12 7.5,127.43,127.40,118.1,114.6,99.2,80.3,78.0,77.3,74.7,73.,73.1,72.9,72.6,71.8,71.6,68.2,66.6,55.6,42.4,20.2.

[0167] II. Synthesize compounds 2-8 according to the following synthetic route.

[0168] Synthetic compound 2-25

[0169]

[0170] The synthesis of compounds 2-25 was performed using the method described in the literature: Alex, C.; Visansirikul, S.; Zhang, Y.; Yasomanee, JP; et al. Carbohydr Res. 2020, 488, 107900.

[0171] Synthetic compound 2-26

[0172]

[0173] The synthesis of compounds 2-26 was performed using the method described in the literature: Alex, C.; Visansirikul, S.; Zhang, Y.; Yasomanee, JP; et al. Carbohydr Res. 2020, 488, 107900.

[0174] Synthetic compound 2-27

[0175]

[0176] The synthesis of compound 2-27 was performed using the method described in the literature: Brand, C.; Kettelhoit, K.; Werz, D.B. Org. Lett. 2012, 14, 5126-5129.

[0177] Synthetic compound 2-28

[0178]

[0179] Compound 2-27 (5.0 g, 11.7 mmol, 1 eq) was dissolved in Py (11.4 mL, 140.4 mmol, 12 eq) and 50 mL of DCM. Tf₂O (11.9 mL, 70.2 mmol, 6 eq) was added at -10 °C, and the temperature was slowly increased to 10 °C over 2 h. After reacting for 18 h, the reaction was confirmed to be complete by TLC. The reaction solution was quenched in ice water, extracted with DCM, and the organic phase was washed with water, saturated NaHCO₃, and saturated NaCl. The mixture was dried over anhydrous Na₂SO₄, filtered, concentrated under reduced pressure, and dried by an oil pump to obtain the crude product. The crude product was dissolved in 15 mL of dry CH₃CN and cooled to -30 °C. TBAN₃ (3.16 g, 11.1 mmol, 0.95 eq) was dissolved in 5 mL of dry CH₃CN and slowly added to the reaction solution. The reaction was carried out at -30 °C for 28 h, and the reaction was confirmed to be complete by TLC. NH3·MeOH (7M, 10.0 mL) was added to the reaction solution, and the reaction solution was slowly heated to 5 °C and reacted for 24 h. The reaction was confirmed to be complete by TLC, and the reaction solution was concentrated under reduced pressure to obtain the crude product. The obtained crude product was dissolved in 25 mL of dry THF, cooled to 0 °C, and TCACl (2.6 mL, 23.4 mmol, 2 eq) and TEA (6.5 mL, 46.8 mmol, 4 eq) were added sequentially. The reaction was then carried out at room temperature for 1.5 h. The reaction was confirmed to be complete by TLC, and the reaction was quenched by adding saturated NaHCO3. The product was extracted with EA, washed with water and saturated NaCl, filtered, dried over anhydrous Na2SO4, filtered again, and separated by column chromatography under reduced pressure (PE / EA = 60:1) to obtain 2-28 (3.6 g, 6.1 mmol, 52%). 1H NMR (400MHz, CDCl3) δ7.51(d,J=8.1Hz,2H),7.18(d,J=7.9Hz,2H),6.26(d,J=9.8Hz,1H),4.33(d,J=10.0 Hz,1H),4.18-4.09(m,1H),2.99(t,J=9.8Hz,1H),2.37(s,3H),1.25(d,J=7.4Hz,3H),1.21-0.99(m,21H). 13 C NMR(100MHz, CDCl3)δ162.3,139.5,135.5,130.2,125.5,92.6,85.5,74.3,73.6,63.7,55.7,21.3,18.1,18.1,18.0,17.1,12.7,12.7.HRMS(ESI)Calculated for C 24 H 38 Cl3N4O3SSi[M+H] + 595.1494, found 595.1439.

[0180] Synthetic compound 2-29

[0181]

[0182] Compound 2-28 (3.6 g, 6.1 mmol) was dissolved in 30 mL of dry DCM and cooled to 0 °C. NIS (2.7 g, 12.2 mmol, 2 eq) and TFA (1.0 mL, 25.3 mmol, 2.5 eq) were added sequentially. The reaction was carried out at 0 °C for 8 min. The reaction was detected by TLC to be complete. The reaction was quenched with Na2S2O3, extracted with DCM, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, and separated by vacuum concentration column chromatography (PE / EA = 7:1) to obtain 2-29 (2.2 g, 4.5 mmol, 74%). 1H NMR(400MHz, CDCl3) δ6.78(t,J=10.5Hz,1H),5.39(d,J=3.6Hz,0.3H),4.64(d,J=8.0Hz,0 .7H),4.47-4.34(m,0.7H),4.30(dd,J=9.7,4.3Hz,0.0.3H),4.24-4.18(m,0.6H),3.82(dd ,J=10.1,4.6Hz,0.7H),3.76-3.70(m,0.7H),3.29(dd,J=10.2,3.6Hz,0.3H),3.15(dd,J= 10.0,8.0Hz,0.7H),1.26(d,J=6.4Hz,2.1H),1.20(d,J=6.5Hz,0.9H),1.19-0.76(m,21H). 13 C NMR (100MHz, CDCl3) δ162.62,162.57,96.8,92.7,92.1,77.2,71.7,70.2,68.6,66.9,65.6,6 3.2,56.5,55.6,18.1,18.1,18.04,18.00,16.6,16.6,12.8,12.7.HRMS(ESI)Calculatedfor C 17 H 32 Cl3N4O4Si[M+H] + 489.1253, found 489.1258.

[0183] Synthetic compounds 2-8

[0184]

[0185] Compound 2-29 (2.2 g, 4.5 mmol) was dissolved in 20 mL of Acetone and cooled to 0 °C. Cs₂CO₃ (2.9 g, 9.0 mmol, 2 eq) and PTFAI (1.1 mL, 6.8 mmol, 1.5 eq) were added sequentially. The reaction was allowed to proceed at room temperature for 2 h. The reaction was confirmed to be complete by TLC. TEA was added to quench the reaction. The mixture was then separated by concentrated column chromatography under reduced pressure (PE / EA = 60:1) to give 2-8 (2.5 g, 3.8 mmol, 84%). 1HNMR(400MHz, Acetone-d6)δ7.36(t,J=7.8Hz,2H),7.15(t,J=7.4Hz,1H),6.91(d,J=7.5Hz,2H),5.92-5.39(m,1H), 4.17(s,1H),3.98(s,1H),3.77(t,J=8.7Hz,1H),2.80(d,J=13.2Hz,1H),1.31(d,J=6.3Hz,3H),1.28-1.07(m,21H). 13 C NMR (100MHz, Acetone-d6) δ205.4,205.2,205.0,143.4,128.8,124.5,119.1,96.4,73 .2,70.1,65.6,64.5,17.6,17.5,16.5,12.8,12.5,12.2,12.0.HRMS(ESI)Calculated for C 25 H 36 Cl3F3N5O4Si[M+H] + 660.1549, found 660.1553.

[0186] III. Synthesize compounds 2-5 (including 2-5a and 2-5b) according to the following synthetic route.

[0187] Synthetic compound 2-48

[0188]

[0189] Compounds 2-8 (500.0 mg, 0.74 mmol, 1.2 eq) and 2-7a (473.0 mg, 0.62 mmol) were dissolved in 6 mL of LDCM. MS drying and dehydration), add freshly activated MS, cooled to -40℃ and stirred for 10 min, then TBSOTf (27.6 μL, 0.12 mmol, 0.2 eq) was added, and the reaction was carried out at -20℃ for 4 h. TLC analysis showed the reaction was complete. TEA was added to quench the reaction, and the mixture was separated by concentration column chromatography (PE / EA = 10:1) to give a white solid 2-48 (550.7 mg, 0.446 mmol, 72%). [α] D 25 = +75.5(c1.0,CHCl3). 11H NMR (400 MHz, CDCl3) δ 7.41 - 7.19 (m, 20H), 7.00 - 6.94 (m, 2H), 6.81 - 6.75 (m, 2H), 6.72 (d, J = 9.6 Hz, 1H), 5.29 (s, 1H), 5.23 (d, J = 3.4 Hz, 1H), 5.10 - 4.97 (m, 2H), 4.85 (d, J = 10.8 Hz, 1H), 4.77 (s, 2H), 4.64 (d, J = 10.8 Hz, 1H), 4.38 (s, 2H), 4.37 - 4.32 (m, 1H), 4.32 - 4.21 (m, 2H), 4.10 (d, J = 6.9 Hz, 4H), 3.97 (d, J = 7.2 Hz, 1H), 3.88 (t, J = 5.4 Hz, 1H), 3.73 (s, 3H), 3.63 - 3.48 (m, 2H), 3.22 (dd, J = 10.3, 3.4 Hz, 1H), 2.74 (dd, J = 15.3, 6.2 Hz, 1H), 2.39 (dd, J = 15.3, 6.7 Hz, 1H), 1.19 - 1.07 (m, 27H). 13 13C NMR (100 MHz, CDCl3) δ 171.2, 162.5, 155.3, 150.2, 138.44, 138.42, 138.40, 136.0, 128.54, 128.45, 128.4, 128.36, 128.29, 128.25, 128.22, 128.1, 127.7, 127.6, 127.5, 127.4, 已解决。 118.4, 114.7, 99.5, 98.5, 92.8, <77.5, 76.1, 74.74, 74.67, 73.2, 73.1, 72.7, 72.4, 70.9, 68.1, 66.2, 65.8, 62.5, 56.5, 55.7, 42.1, 20.8, 18.2, 18.1, 16.5, 12.9. HRMS (ESI) Calculated for C 63 H 79 Cl3N4O 13 SiNa [M + Na] + 1255.4371, found 1255.4379.

[0190] Synthesize compound 2 - 49

[0191]

[0192] It should be noted that there seems to be an incomplete part in the translation of the 13C NMR content in line 2. You may need to check and correct it according to the actual situation.Compound 2-48 (550.7 mg, 0.446 mmol) was dissolved in a mixed solvent of 4 mL CH3CN and 1 mL H2O. CAN (734.6 mg, 1.34 mmol, 3 eq) was added at 0 °C, and the mixture was reacted at room temperature for 3 h. The reaction was confirmed to be complete by TLC. The reaction was quenched with saturated Na2S2O3, extracted with EA, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, and evaporated to dryness. The mixture was then separated by column chromatography (PE / EA = 3:1) to give a colorless liquid 2-49 (372.5 mg, 0.33 mmol, 78%). [α] D 25 = +66.4 (c 1.0, CHCl3). 1 H NMR (600MHz, CDCl3) δ7.41-7.19(m,20H),6.70(dd,J=13.0,9.7Hz,1H),5.24(d,J=3.9Hz,1H),5.14(d,J= 1.8Hz,1H),5.05(dd,J=6.1,3.0Hz,3H),4.85(d,J=11.0Hz,1H),4.72(s,2H),4.62(t,J=11.0Hz,2H),4.4 4-4.36(m,3H),4.31(dd,J=10.4,4.5Hz,1H),4.29-4.24(m,1H),4.22-4.13(m,2H),4.02-3.92(m,5H),3. 68-3.47(m,3H),3.21(dd,J=10.4,3.9Hz,1H),2.78-2.71(m,1H),2.46-2.40(m,1H),1.27-1.05(m,27H). 13C NMR (150MHz, CDCl3) δ171.3,171.2,162.6,138.4,138.3,137.9,135.92,135.89,128.5,128.44,128.42,128.39,128 .37,128.34,128.24,128.22,128.1,127.8,127.71,127.66,127.61,127.57,127.5,127.4,99.1,98.9,94.0,93.5,9 2.8,79.7,77.6,76.0,75.7,74.78,74.75,74.2,73.5,73.2,73.2,72.6,72.5,72.2,70.6,70.5,68.4,68.1,66.7,66.2,65.7,62.8,62.5,56.5,56.3,42.3,42.1,20.8,20.7,18.21,18.16,18.14,18.11,16.5,16.33,13.07,12.9,12.7.

[0193] Synthetic compound 2-5a

[0194]

[0195] Compound 2-49 (372.5 mg, 0.33 mmol) was dissolved in 3.3 mL of Lacetone, cooled to 0 °C, and then Cs₂CO₃ (215.0 mg, 0.66 mmol, 2.0 eq) and PTFAI (87.8 μL, 0.495 mmol, 1.5 eq) were added sequentially. The mixture was gradually restored to room temperature and reacted for 2 h. The reaction was confirmed to be complete by TLC. The reaction was quenched by the addition of TEA, and the mixture was separated by reduced pressure concentration column chromatography (PE / EA = 20:1) to obtain a colorless viscous liquid 2-5a (334.0 mg, 0.257 mmol, 78%). [α] D 25 = +50.2(c 1.0, CHCl3). 11H NMR (400 MHz, Acetone-d6) δ 7.55 - 7.42 (m, 3.3H), 7.39 - 7.23 (m, 22.2H), 7.16 - 7.10 (m, 1.1H), 6.90 (d, J = 7.8 Hz, 2.2H), 5.37 (d, J = 3.9 Hz, 1.1H), 5.09 (d, J = 1.0 Hz, 2.2H), 4.90 (d, J = 11.0 Hz, 1.1H), 4.85 (d, J = 11.8 Hz, 1.1H), 4.75 (s, 1.1H), 4.69 (d, J = 11.0 Hz, 1.1H), 4.48 - 4.40 (m, 4.4H), 4.37 (s, 1H), 4.26 - 4.15 (m, 2.2H), 4.05 - 3.92 (m, 4.4H), 3.65 (dd, J = 10.1, 5.4 Hz, 1.1H), 3.57 (dd, J = 10.1, 6.5 Hz, 1.1H), 2.72 (dd, J = 15.3, 7.1 Hz, 1.1H), 2.52 (dd, J = 15.3, 6.0 Hz, 1.1H), 1.27 (d, J = 6.1 Hz, 3.3H), 1.23 - 1.10 (m, 23.1H), 1.08 (d, J = 6.4 Hz, 3.3H). 13 13C NMR (100 MHz, Acetone-d6) δ 206.5, 206.3, 206.1, 171.5, 163.4, 163.3, 144.6, 139.6, 139.5, 139.43, 137.38, 129.7, 129.3, <129.1, 129.09, 129.06, 129.03, 128.9, 128.8, 128.5, 128.4, 128.3, 128..2, 128.1, 125.2, 120.2, 78.0, 76.2, 75.2, 74.8, 74.2, 73.6, 73.2, 72.8, 71.4, 69.1, 66.9, 66.5, 62.8, 57.5, 57.4, 42.8, 21. .1, 18.7, 18.6, 16.7, 13.6. HRMS (ESI) Calculated for C 64 H 77 Cl3F3N5O 12 SiNa [M + Na] + [[ID=,10]]12320.4248, found 12320.4246.

[0196] Synthesis of Compound 2 - 56

[0197]

[0198] Compounds 2-8 (500.0 mg, 0.74 mmol, 1.2 eq) and 2-7b (473.0 mg, 0.62 mmol) were dissolved in 6 mL of LDCM. MS drying and dehydration), add freshly activated MS, cooled to -40℃ and stirred for 10 min, then TBSOTf (27.6 μL, 0.12 mmol, 0.2 eq) was added, and the reaction was carried out at -20℃ for 4 h. The reaction was confirmed to be complete by TLC. The reaction was quenched by TEA, and the product was separated by vacuum concentration column chromatography (PE / EA = 10:1) to give a white solid 2-56 (550.7 mg, 0.446 mmol, 72%). [α] D 25 = +74.9 (c 1.0, CHCl3). 1 H NMR (400MHz, CDCl3) δ7.55-7.17(m,20H),7.03-6.89(m,2H),6.79-6.74(m,2H),6.71(d,J=9.6Hz,1H),5.26(d,J=5.7Hz, 1H),5.22(d,J=3.9Hz,1H),4.96(q,2H),4.87(d,J=11.0Hz,1H),4.76(s,2H),4.61(d,J=9.8Hz,1H),4.42(s,2H),4.38(dd ,J=10.4,4.4Hz,1H),4.33-4.22(m,2H),4.12-3.95(m,5H),3.92-3.85(m,1H),3.70(s,3H),3.65-3.53(m,2H),3.22(dd,J =10.4,3.9Hz,1H),2.58(dd,J=15.3,5.6Hz,1H),2.30(dd,J=15.3,7.5Hz,1H),1.20(d,J=6.0Hz,4H),1.19-1.07(m,23H). 13C NMR (100MHz, CDCl3) δ171.0,162.5,155.3,150.3,138.5,138.4,138.3,136.0,128.52,1 28.45,128.4,128.3,128.2,128.13,128.11,127.67,127.65,127.5,127.4,127.3,118. 5,114.6,99.4,98.6,92.8,77.0,76.0,74.8,74.6,73.19,73.16,72.6,72.2,70.8,68.1 ,66.1,65.9,62.6,56.5,55.6,42.2,20.6,18.2,18.1,16.5,12.9.HRMS(ESI)Calculated for C 63 H 79 Cl3N4O 13 SiNa[M+Na] + 1255.4371, found 1255.4373.

[0199] Synthetic compound 2-57

[0200]

[0201] Compound 2-56 (550.7 mg, 0.446 mmol) was dissolved in a mixed solvent of 4 mL CH3CN and 1 mL H2O. CAN (734.6 mg, 1.34 mmol, 3 eq) was added at 0 °C, and the mixture was reacted at room temperature for 3 h. The reaction was confirmed to be complete by TLC. The reaction was quenched with saturated Na2S2O3, extracted with EA, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, and separated by vacuum concentration column chromatography (PE / EA = 3:1) to give a colorless liquid 2-57 (372.5 mg, 0.33 mmol, 78%). [α] D 25 = +66.9(c1.0,CHCl3). 11H NMR(400MHz,CDCl3)δ7.40 - 7.23(m,20H),6.71(d,J = 9.5Hz,1H),5.25(d,J = 3.9Hz,1H),5.15 - 5.06(m,2H),5.00(d,J = 1.8Hz,1H),4.86(d,J = 11.1Hz,1H),4.72(s,2H),4.57(d,J = 11.1Hz,1H),4.53 - 4.45(m,2H),4.32(dd,J = 10.4,4.4Hz,1H),4.30 - 4.23(m,2H),4.17 - 4.11(m,1H),4.11 - 4.02(m,2H),4.02 - 3.98(m,1H),3.98 - 3.94(m,1H),3.91(t,J = 9.6Hz,1H),3.73 - 3.64(m,2H),3.59(dd,J = 10.9,7.7Hz,1H),3.18(dd,J = 10.4,3.8Hz,1H),2.68(dd,J = 16.1,9.7Hz,1H),2.46(dd,J = 16.1,3.2Hz,1H),1.22 - 1.07(m,27H). 13 13C NMR(100MHz,CDCl3)δ172.4,162.5,138.6,138.4,138.3,135.6,128.6,128.45,128.39,128.3,128.2,128.1,128.0,127.7,127.62,127.57,127.4,127.35,127.31,98.8,93.8,92.8,77.2,75.1,75.0,74.83,74.80,73.2,72.5,70.2,69.6,69.4,68.0,66.5,65.7,62.4,56.6,42.0,19.5,18.22,18.16,18.1,16.5,12.9.

[0202] Synthesize compound 2 - 5b

[0203]

[0204] Compound 2-57 (372.5 mg, 0.33 mmol) was dissolved in 3.3 mL of Lacetone, cooled to 0 °C, and then Cs₂CO₃ (215.0 mg, 0.66 mmol, 2 eq) and PTFAI (87.8 μL, 0.495 mmol, 1.5 eq) were added sequentially. The mixture was gradually restored to room temperature and reacted for 2 h. The reaction was confirmed to be complete by TLC. The reaction was quenched by the addition of TEA, and the mixture was separated by concentrated column chromatography under reduced pressure (PE / EA = 20:1) to give a colorless viscous liquid 2-5b (334.0 mg, 0.257 mmol, 78%). [α] D 25 = +51.8(c 1.0, Acetone). 1 H NMR (400MHz, Acetone-d6) δ7.55-7.44(m,3.3H),7.39-7.23(m,22H),7.12-7.07(m,.11H),6.87(d,J=7.8Hz,.2.2H),5.35(d, J=3.9Hz,1.1H),5.14(q,2.2H),4.94(d,J=11.0Hz,1.1H),4.85(d,J=11.8Hz,1.1H),4.77(d,J=11.8Hz,1.1H),4.69(d,J=11. 1Hz,1.1H),4.53-4.43(m,4.4H),4.35(s,1.1H),4.22-4.13(m,2.2H),4.06-3.91(m,4.4H),3.72-3.56(m,2.2H),2.73(dd,J= 15.2, 6.4Hz, 1.1H), 2.46 (dd, J=15.3, 6.5Hz, 1.1H), 1.25 (d, J=6.1Hz, 3.3H), 1.23-1.11 (m, 23.1H), 1.06 (d, J=6.4Hz, 3.3H). 13C NMR (100MHz, Acetone-d6) δ206.3,171.4,163.3,163.2,144.6,139.6,139.39,139.37,13 7.33,129.6,129.2,129.12,129.07,129.0,128.95,128.91,128.87,128.8,128.5,128.4 0,128.36,128.14,128.08,125.2,120.2,100.3,93.9,77.9,76.2,75.3,74.7,74.5,73.6,73.1,72.7,71.7,69.1,66.9,66.5,62.9,57.5,57.4,42.9,21.1,18.7,18.6,16.7,13.6.

[0205] IV. Synthesize compounds 2-9 according to the following synthetic route.

[0206] The synthesis methods of compounds 2-9 were adopted from the literature: Guo Kaiyan. Study on glycosylation of dimethylamino sugar receptor activated by hydrogen bond [D]. Jiangxi Normal University. and Zhou Meimei. Study on synthesis of Escherichia coli serotype 64 dithioO-antigen and zwitterionic polysaccharide PS A2 fragment [D]. Jiangxi Normal University.

[0207] V. Synthesize compound 2-10 according to the following synthetic route.

[0208] The method for synthesizing compound 2-41 was adopted from the literature: Zhou Meimei. Study on the synthesis of Escherichia coli serotype 64 disulfide O-antigen and zwitterionic polysaccharide PS A2 fragment [D]. Jiangxi Normal University.

[0209] Synthetic compound 2-42

[0210]

[0211] Compound 2-41 (11.5 g, 20.4 mmol) was dissolved in 110 mL of dry DMF and cooled to 0 °C. 2,6-lutidine (4.8 mL, 40.8 mmol, 2 eq) and TBSOTf (7.0 mL, 30.6 mmol, 1.5 eq) were added sequentially. The mixture was reacted at room temperature for 10 h. The reaction was confirmed to be complete by TLC. The reaction solution was quenched in ice water, extracted with EA, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, and evaporated to dryness. The mixture was separated by column chromatography (PE / EA = 5:1) to give a white solid 2-42 (8.8 g, 15.1 mmol, 74%). 1HNMR(400MHz, CDCl3)δ7.79(d,J=8.3Hz,2H),7.27(d,J=8.1Hz,2H),6.96-6.90(m,2H),6.86- 6.80(m,2H),5.04(dd,J=9.8,8.0Hz,1H),4.82(d,J=7.9Hz,1H),4.37(dd,J=10.8,1.8Hz,1H) ,4.17(dd,J=10.8,5.9Hz,1H),3.81(s,3H),3.67-3.56(m,1H),3.55-3.44(m,2H),2.93-2.76 (m,2H),2.75-2.61(m,2H),2.41(s,3H),2.23(s,3H),0.93(s,9H),0.24(s,3H),0.15(s,3H). 13 C NMR (100MHz, CDCl3) δ205.9,171.3,155.7,151.1,145.0,132.6,129.8,128.0,118.7,114.5,100.3,75 .0,71.8,69.3,68.2,68.0,55.6,37.7,29.8,27.8,25.8,21.6,18.0,-4.3,-4.8.HRMS(ESI)Calculated for C 31 H 43 N3O 10 SSiNa[M+Na] + 700.2331, found 700.2331.

[0212] Synthetic compound 2-43

[0213]

[0214] Compound 2-42 (9.4 g, 16.2 mmol) was dissolved in 47 mL of dry Acetone, and NaI (7.5 g, 51.7 mmol, 3 eq) was added. The mixture was reacted overnight at 65 °C. The reaction was confirmed to be complete by TLC. The product was filtered and evaporated to dryness. The concentrated crude product was dissolved in EA, washed with water and saturated NaCl, dried over anhydrous Na2SO4, and filtered and evaporated to dryness. The resulting crude product was dissolved in 324 mL of dry Toluene, and AIBN (532.0 mg, 3.2 mmol, 3 eq) was added. The mixture was heated to 80 °C, and then n-Bu3SnH (13.8 mL, 48.6 mmol, 0.2 eq) was added. The reaction was allowed to proceed for 1.5 h. The reaction was confirmed to be complete by TLC. The product was separated by concentrated column chromatography under reduced pressure (PE / EA = 3:1) to give a white solid 2-43 (4.3 g, 8.7 mmol, 54%).

[0215] Synthetic compound 2-44

[0216]

[0217] Compound 2-43 (5.5 g, 11.4 mmol) was dissolved in 55 mL of dry THF, cooled to 0 °C, and then TEA (3.2 mL, 22.8 mmol, 2.0 eq) and TCACl (1.8 mL, 17.1 mmol, 1.5 eq) were added sequentially. The reaction was allowed to proceed at room temperature for 1.5 h. The reaction was confirmed to be complete by TLC. The reaction was quenched with water, extracted with EA, and the organic phase was washed with water and saturated NaCl. The mixture was dried over anhydrous Na₂SO₄, filtered, and separated by vacuum concentration column chromatography (PE / EA = 7:1) to give a white solid 2-44 (6.15 g, 9.6 mmol, 84%). [α] D 25 = -19.1 (c 1.0, CHCl3). 1 H NMR (400MHz, CDCl3) δ6.99-6.97(m,2H),6.89(d,J=9.6Hz,1H),6.83-6.81(m,2H) ,5.08(dd,J=10.6,7.7Hz,1H),4.97(d,J=7.7Hz,1H),4.19(q,J=19.8,9.6Hz,1H) ,3.77(s,3H),3.63-3.54(m,1H),3.54-3.47(m,1H),2.81-2.66(m,2H),2.66-2.5 2(m,2H),2.15(s,3H),1.35(d,J=6.1Hz,3H),0.87(s,9H),0.09(d,J=3.5Hz,6H). 13 C NMR (100MHz, CDCl3) δ206.1,172.4,162.3,155.7,151.3,118.8,114.7,100.5,92.5,74.6,7 4.4,72.0,58.4,55.8,37.9,30.0,28.0,25.9,18.8,18.0,-3.5,-3.6.HRMS(ESI)Calculated forC 26 H 38 Cl3NO8Si[M+Na] + 648.1325, found 648.1320.

[0218] Synthetic compound 2-45

[0219]

[0220] Compound 2-44 (3.5 g, 5.6 mmol) was dissolved in a mixed solvent of 44 mL CH3CN and 11 mL H2O, cooled to 0 °C, and CAN (9.2 g, 16.8 mmol, 3 eq) was added. The reaction was allowed to proceed at room temperature for 2.5 h, and TLC was used to confirm complete reaction. The reaction was quenched with saturated Na2S2O3, extracted with EA, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, and evaporated to dryness. The mixture was then separated by column chromatography (PE / EA = 3:1) to give a colorless liquid 2-45 (2.4 g, 4.4 mmol, 78%). [α] D 25 = +88.5 (c 1.0, CHCl3). 1 H NMR (400MHz, CDCl3) δ6.60(d,J=9.5Hz,1H),5.19(d,J=3.4Hz,1H),4.85-4.73(m,1H),4.28(q,J=10.0Hz,1H),4.07-3.89(m,2H),3.49-3.31 (m,2H),2.69-2.58(m,2H),2.54-2.41(m,2H),2.09(d,J=11.8Hz,3H),1.16(d,J=6.1Hz,3H),0.77(d,J=3.3Hz,9H),-0.01(d,J=6.0Hz,6H). 13 C NMR (100MHz, CDCl3) δ207.6,206.6,173.0,172.4,162.2,162.0,95.5,92.6,89.4,74.7,74.1,71.8,68.6,58.4, 54.7,37.9,37.8,29.9,29.8,28.1,25.79,25.76,18.44,18.41,18.01,17.9,-3.6,-3.7.HRMS(ESI)Calculated for C 19 H 32 Cl3NO7SiNa[M+Na] + 542.0906, found 542.0904.

[0221] Synthetic compound 2-46

[0222]

[0223] Compound 2-46 (917.9 mg, 1.3 mmol) and 5-azidopentanol (251.9 mg, 2.0 mmol, 1.5 eq) were dissolved in 13 mL of DCM. MS drying and dehydration), add freshly activated MS, cooled to -20℃ and stirred for 10 min, then added TBSOTf (59.7 μL, 0.26 mmol, 0.2 eq), reacted at -20℃ for 4 h, and the reaction was confirmed to be complete by TLC. The reaction was quenched by adding TEA, and separated by concentrated column chromatography (PE / EA = 5:1) to obtain a colorless viscous liquid compound 2-47 (678.4 mg, 1.05 mmol, 81%). 1 H NMR(400MHz, CDCl3) δ6.70(d,J=9.6Hz,1H),4.83-4.75(m,1H),4.49(d,J=7.6Hz,1H),4. 10(dd,J=19.7,9.6Hz,1H),3.90-3.80(m,1H),3.55-3.42(m,2H),3.42-3.35(m,1H),3.2 8(t,J=6.9Hz,2H),2.79-2.64(m,2H),2.63-2.57(m,2H),2.17(s,3H),1.68-1.56(m,6H) ,1.45(dd,J=13.5,6.4Hz,2H),1.31(d,J=6.1Hz,3H),0.86(s,9H),0.08(d,J=7.8Hz,6H). 13 C NMR (100MHz, CDCl3) δ206.0,172.2,162.0,100.7,92.4,74.7,74.0,72.1,69.5,58.3,51. 4,37.6,29.9,29.0,28.6,27.8,25.8,23.2,18.6,17.9,-3.6,-3.7.HRMS(ESI)Calculated for C 24 H 41 Cl3N4O7SiNa[M+Na] + 653.1702, found 653.1700.

[0224] Synthetic compound 2-10

[0225]

[0226] Compound 2-47 (300.0 mg, 0.49 mmol) was dissolved in a mixed solvent of 15 mL Py and 15 mL THF. HF / Py (1.5 mL) was added at 0 °C, and the reaction was carried out at 40 °C for 28 h. The reaction was confirmed to be complete by TLC. The pH was adjusted to weakly alkaline by adding NaHCO3, and the mixture was filtered. Separation was achieved by concentrated column chromatography (PE / EA = 2:1) to give a white solid 2-10 (212.7 mg, 0.040 mmol, 82%). [α] D 25= ±37.7 (c 1.0, CHCl3). 1 H NMR (400MHz, CDCl3) δ7.36-7.23(m,1H),4.88-4.78(m,1H),4.52(d,J=7.8Hz, 1H),4.12-3.98(m,1H),3.87(dt,J=9.6,6.3Hz,1H),3.60-3.42(m,2H),3.35( dd,J=18.0,8.6Hz,1H),3.32-3.22(m,2H),2.75-2.69(m,2H),2.63-2.56(m,2 H),2.17(s,3H),1.67-1.57(m,4H),1.50-1.39(m,2H),1.36(d,J=6.1Hz,3H). 13 C NMR (100MHz, CDCl3) δ205.9,173.0,164.1,100.5,92.1,75.2,73.4,71.6,69.5, 58.8,51.4,37.76,29.75,29.01,28.6,27.9,23.2,17.5.HRMS(ESI)Calculated for C 18 H 27 Cl3N4O7Na[M+Na] + 539.0837, found 539.0837.

[0227] VI. Synthesize compounds 2-6 according to the following synthetic route.

[0228] Synthetic compound 2-50

[0229]

[0230] Compounds 2-9 (1271.9 mg, 1.79 mmol, 1.4 eq) and 2-10 (662.8 mg, 1.28 mmol) were dissolved in 13 mL of LDCM. MS drying and dehydration), add freshly activated MS, cooled to -20℃ and stirred for 10 min, then TBSOTf (59.7 μL, 0.26 mmol, 0.2 eq) was added, and the reaction was carried out at -20℃ for 4 h. TLC analysis showed the reaction was complete. TEA was added to quench the reaction, and the mixture was separated by concentration column chromatography (PE / EA = 10:1) to give a white solid 2-50 (489.1 mg, 0.446 mmol, 72%). [α] D 25 = -17.7 (c1.0, CHCl3). 11H NMR (400 MHz, CDCl3) δ 7.86 - 7.75 (m, 4H), 7.51 - 7.41 (m, 3H), 7.29 - 7.17 (m, 5H), 6.84 (d, J = 7.6 Hz, 1H), 5.22 (d, J = 2.7 Hz, 1H), 4.87 (dd, J = 14.7, 7.2 Hz, 2H), 4.79 (d, J = 11.1 Hz, 1H), 4.64 (d, J = 11.2 Hz, 1H), 4.55 (d, J = 11.1 Hz, 1H), 4.47 (d, J = 7.6 Hz, 1H), 4.44 - 4.39 (m, 1H), 4.34 (dd, J = 11.6, 4.6 Hz, 1H), 4.22 - 4.08 (m, 3H), 4.01 - 3.94 (m, 1H), 3.89 - 3.81 (m, 1H), 3.55 - 3.44 (m, 4H), 3.27 (t, J = 6.8 Hz, 2H), 2.75 - 2.65 (m, 2H), 2.65 - 2.54 (m, 2H), 2.16 (s, 3H), 1.98 (s, 3H), 1.66 - 1.56 (m, 4H), 1.49 - 1.40 (m, 2H), 1.38 (d, J = 4.8 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 205.9, 172.2, 170.7, 162.6, 161.8, 137.3, 134.7, 133.3, 133.1, 128.5, 128.4, 128.3, 128.1, 128.0, 127.7, 127.4, 126.3, 126.2, 126.1, 100.5, 92.5, 92.4, 72.2, 72.0, 71.9, 71.4, 69.6, 62.6, 57.3, 52.0, 51.4, 37.7, 29.8, 29.0, 28.6, 27.8, 23.2, 20.8, 18.3. HRMS (ESI) Calculated for C 46 1H 53 16Cl6N5O 13 [M + Na] + 1116.1663, found​​​​​​​​Compound 2-50 (107.5 mg, 0.098 mmol) was dissolved in a mixed solvent of 1 mL DCM and 0.1 mL H2O. 0.1 mL buffer (pH = 7) and DDQ (45.4 mg, 0.2 mmol, 2 eq) were added sequentially at 0 °C. The reaction was allowed to proceed for 3 h at room temperature. TLC was used to confirm the completeness of the reaction. The reaction was quenched with saturated Na2S2O3, extracted with DCM, washed with water and saturated NaCl, dried over anhydrous Na2SO4, filtered, and separated by vacuum concentration column chromatography (PE / EA = 2:1) to obtain a white solid 2-6 (65.6 mg, 0.069 mmol, 70%). 1 H NMR (400MHz, CDCl3) δ7.64(d,J=9.0Hz,1H),7.33-7.27(m,5H),6.71(d,J=8.3Hz,1H),5.12(d,J=1.9Hz,1H),5.02(dd,J=10.5,7.6Hz,1H), 4.82(d,J=11.2Hz,1H),4.66(d,J=11.2Hz,1H),4.52(d,J=7.6Hz,1H),4.32(dd,J=7.6,3.6Hz,1H),4.27(d,J=9.8Hz,1H),4.25-4.16(m,3H) ,3.97-3.91(m,1H),3.91-3.83(m,1H),3.73(t,J=9.2Hz,1H),3.64-3.55(m,1H),3.53-3.47(m,1H),3.44(t,J=9.2Hz,1H),3.24(t,J=6.8H z,2H),2.94(d,J=2.9Hz,1H),2.71(t,J=6.2Hz,2H),2.59(t,J=6.3Hz,2H),2.17(s,3H),1.96(s,3H),1.69-1.51(m,4H),1.49-1.31(m,5H). 13 C NMR (100MHz, CDCl3) δ205.7,172.1,170.5,162.9,162.1,137.5,128.6,128.5,128.1,100.6,99.0,92.5,92.2,80.8,74.6, 73.1,71.8,71.2,70.5,69.7,62.8,57.4,55.7,51.3,37.7,29.8,28.9,28.5,27.9,23.1,20.7,18.1.HRMS(ESI)Calculated for C 35 H 45 Cl6N5O 13 Na[M+Na]+ 976.1038, found 976.1038.

[0234] VII. Synthesize compounds 2-3 (including 2-3a and 2-3b) according to the following synthetic route.

[0235] Synthetic compound 2-51a

[0236]

[0237] Compounds 2-5a (81.6 mg, 0.0628 mmol, 1.2 eq) and 2-6 (50.0 mg, 0.0523 mmol) were dissolved in 1 mL of LCM. MS drying and dehydration), add freshly activated MS, cooled to -20℃ and stirred for 10 min, then TBSOTf (3.0 μL, 0.013 mmol, 0.2 eq) was added, and the reaction was carried out at -20℃ for 4 h. TLC analysis showed the reaction was complete. TEA was added to quench the reaction, and the mixture was separated by reduced pressure column chromatography (PE / EA = 4:1) to give a white solid 2-51a (75.7 mg, 0.0366 mmol, 70%). HRMS (ESI) Calculated for C 91 H 116 Cl9N9O 24 SiNa[M+Na] + 2084.4991, found 2084.4985.

[0238] Synthesize compound 2-3a

[0239]

[0240] Compound 2-51a (75.7 mg, 0.0366 mmol) was dissolved in a mixed solution of 0.2 mL AcOH and 0.8 mL Py. 80% hydrazine hydrate (3.5 μL, 0.072 mmol, 2 eq) was added at 0 °C, and the reaction was carried out at room temperature for 35 min. The reaction was confirmed to be complete by TLC. The solution was diluted with EA, washed with water, NaHCO3, and saturated NaCl, dried over anhydrous Na2SO4, filtered, and evaporated to dryness. The solution was then separated by column chromatography (PE / EA = 4:1) to give a white solid 2-3a (56.1 g, 0.0285 mmol, 78%). 11H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 7.3 Hz, 1H), 7.38 - 7.16 (m, 25H), 6.66 (dd, J = 8.7, 5.5 Hz, 2H), 5.11 (dd, J = 9.3, 6.0 Hz, 3H), 5.07 - 5.01 (m, 2H), 4.85 (d, J = 11.4 Hz, 1H), 4.73 (d, J = 11.9 Hz, 1H), 4.69 - 4.58 (m, 3H), 4.44 (dd, J = 11.5, 2.9 Hz, 2H), 4.41 - 4.34 (m, 2H), 4.33 - 4.21 (m, 4H), 4.21 - 4.12 (m, 2H), 4.11 - 4.02 (m, 4H), 3.95 - 3.85 (m, 4H), 3.85 - 3.78 (m, 2H), 3.71 (dd, J = 1,0.2, 4.8 Hz, 2H), 3.61 - 3.52 (m, 2H), 3.52 - 3.39 (m, 3H), 3.26 (t, J = 6.7 Hz, 2H), 3.16 (dd, J = 10.3, 3.9 Hz, / / 1H), 2.77 (dd, J = 7.3, 7.1 Hz, 2H), 2.45 (dd, J = 15.3, 5.6 Hz, 1H), 1.96 (s, 3H), 1.67 - 1.56 (m, 4H), 1.49 - 1.39 (m, 2H), 1.32 (d, J = 6.2 Hz, 3H), 1.26 (d, J = 5.9 Hz, 3H), / / 1.20 - 1.05 (m, 21H), 0.95 (d, J = 6.4 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 171. ,9, 170.3, 162.5, 162.1, 161.2, 138.7, 138.6, 138.1, 136.7, 135.8, 128.6, 128.55, 128.41, 128.37, 128.33, 128.25, 128.2, 128.1, 12 / / 7.8, 127.6, 127.6, 127.49, 127.3, 102.7, 99.2, 97.1, 92.8, 92.7, 92.5, 79.6, 78.2, 77.3, 74.5, 74.4, 74.2, 73.4, 73.1, 72.5, 71.3, 70.7, 70.3, 70.1, 69.4, 68.1, 66.4, 65.8, 62.5, 58.0, / / 56.3, 54.6, 51.3, 42.5, 29.1, 28.6, 23.3, 20.7, / / 20.7, 19.2, 18.2, 18.1, 16.4, 12.8.

[0241] Synthesize compound 2 - 51b

[0242] Note: There seem to be some formatting and potential errors in the original text (like the " / / " in the NMR data which might be incorrect characters). The translation is done based on the best understanding of the provided text.

[0243] Compounds 2-5b (81.6 mg, 0.0628 mmol, 1.2 eq) and 2-6 (50.0 mg, 0.0523 mmol) were dissolved in 1 mL of LCM. MS drying and dehydration), add freshly activated MS, cooled to -20℃ and stirred for 10 min, then added TBSOTf (3.0 μL, 0.013 mmol, 0.2 eq), reacted at -20℃ for 4 h, and the reaction was complete as detected by TLC. The reaction was quenched by adding TEA, and separated by vacuum concentration column chromatography (PE / EA = 4:1) to give a white solid 2-51b (75.7 mg, 0.0366 mmol, 70%). 1 H NMR (400MHz, CDCl3) δ7.80 (s, 1H), 7.39-7.18 (m, 25H), 6.71 (d, J = 8.4Hz, 1H), 6.64 (d, J = 9.6Hz, 1H), 5.23 (d, J = 12.5Hz, 1H), 5.17-5.04 (m, 5H) ,4.84(d,J=11.5Hz,1H),4.70-4.57(m,4H),4.49-4.36(m,5H),4.29-4. 23(m,2H),4.23-3.88(m,11H),3.88-3.79(m,3H),3.70-3.57(m,2H),3. 55-3.43(m,3H),3.26(t,J=6.8Hz,2H),3.15(dd,J=10.4,3.9Hz,1H),2.81(dd,J=14.8,5.9Hz,1H),2.70-2.62(m,2H),2.58-2.43(m,3H),2.12( s,3H),2.00(s,3H),1.65-1.55(m,4H),1.47-1.39(m,2H),1.36(d,J=6. 1Hz,3H),1.28-1.24(m,3H),1.22-1.05(m,21H),0.90(d,J=6.4Hz,3H). 13C NMR (100MHz, CDCl3) δ206.1,171.8,171.7,170.4,162.4,162.1,161.1,138.6,138.55,138.48,136 .8,136.0,128.61,128.57,128.5,128.4,128.3,128.2,128.1,127.9,127.8,127.6,127.5,127.45 ,127.42,127.40,100.6,99.0,92.8,92.7,92.4,74.8,74.3,73.2,72.9,71.5,69.3,68.1,66.6,65.8,62.6,56.3,51.4,37.7,29.8,29.0,28.6,27.7,23.2,21.2,20.8,18.8,18.2,18.1,16.4,12.8.

[0244] Synthetic compound 2-3b

[0245] The synthesis of compound 2-3b differs from that of compound 2-3a in that compound 2-51a is replaced with 2-51b. The structure of the synthesized 2-3b is shown below:

[0246]

[0247] 8. Synthesize compound 2-2 (including 2-2a and 2-2b) according to the following synthetic route.

[0248] Synthesize compound 2-2a

[0249]

[0250] Compounds 2-3a (56.1 mg, 0.0285 mmol) and 2-4 (34.5 mg, 0.057 mmol, 2 eq) were dissolved in 1 mL of DCM ( MS drying and dehydration), add freshly activated MS, cooled to -20℃ and stirred for 10 min, then added TBSOTf (3.0 μL, 0.013 mmol, 0.2 eq), reacted at -20℃ for 4 h, and the reaction was confirmed to be complete by TLC. The reaction was quenched by adding TEA, and separated by concentrated column chromatography (PE / EA = 3:1) to obtain colorless liquid 2-2a (75.7 mg, 0.0366 mmol, 70%). 1H NMR(400MHz,CDCl3)δ7.38-7.17(m,40H),6.82(s,1H),6.66(d,J=9.4Hz,1H),5.13(dd,J=7.6,3.4Hz,2H),5.08(d,J=3.3Hz,1H),5.02(d,J=5.6Hz,3H),4.91(d,J=11.5Hz,1H),4.81(d,J=11.4Hz,1H),4.76(d,J=11.8Hz,1H),4.72-4.70(m,2H),4.67-4.60(m,5H),4.48(d,J=11.9Hz,1H),4.45-4.39(m,2H),4.37-4.31(m,2H),4.27-4.18(m,4H),4.13-3.97(m,7H),3.94-3.81(m,7H),3.71-3.51(m,7H),3.47(dd,J=14.9,6.3Hz,2H),3.23(t,J=6.8Hz,2H),3.15(dd,J=10.2,3.8Hz,1H),2.78(dd,J=7.2,6.3Hz,1H),2.42(dd,J=7.1,6.7Hz,1H),1.97(s,3H),1.66-1.53(m,4H),1.44-1.36(m,2H),1.34(d,J=4.8Hz,3H),1.25(d,J=5.9Hz,3H),1.15-1.06(m,24H),0.98(d,J=6.4Hz,3H). 13C NMR (100MHz, CDCl3) δ171.4,170.3,162.4,161.8,161.2,138.69,138.65 ,138.52,138.50,138.48,138.4,137.0,136.0,128.6,128.5,128.45,128 1.4,128.37,128.31,128.26,128.21,128.16,128.14,128.08,128.0,12 7.8,127.7,127.6,127.50,127.46,127.32,127.30,127.2,102.2,99.0,9 8.2,96.9,92.8,92.6,92.5,79.8,79.5,77.2,76.9,76.6,75.8,74.8,74 .7,74.3,74.2,73.9,73.1,72.9,72.6,72.4,71.4,70.8,70.3,69.6,68.0 ,67.2,66.0,65.8,62.7,62.5,58.1,56.3,51.3,42.4,29.1,28.6,23.2,20.8,20.6,19.0,18.2,18.1,16.8,16.5,12.8,1.0.HRMS(ESI)Calculated for C 113 H 138 Cl9N9O 26 SiNa[M+Na] + 2379.6719, found 2402.6618.

[0251] Synthesize compound 2-2a

[0252] The synthesis of compound 2-2b differs from that of compound 2-2a in that compound 2-3a is replaced with 2-3b. The structure of the synthesized 2-2b is shown below:

[0253]

[0254] IX. Synthesize the zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound 2-1 (including 2-1a and 2-1b) according to the following synthetic route.

[0255] Synthetic compound 2-52a

[0256]

[0257] Compound 2-2a (75.7 mg, 0.0366 mmol) was dissolved in a mixed solution of 1 mL THF and 1 mL Py. HF / Py (0.1 mL) was added at 0 °C, and the reaction was carried out at 40 °C for 48 h. The reaction was confirmed to be complete by TLC. NaHCO3 solid was added to quench the reaction, and the mixture was filtered and evaporated to dryness. The mixture was separated by column chromatography (PE / EA = 3:1) to obtain a colorless liquid 2-52a (50.8 mg, 0.0228 mmol, 80%). 1 H NMR (400MHz, CDCl3) δ7.34-7.21 (m, 40H), 6.80 (s, 1H), 6.66 (d, J = 8.9Hz, 1H), 5.15 (d ,J=3.1Hz,1H),5.05(s,4H),4.89(dd,J=18.4,11.6Hz,3H),4.79-4.74(m,1H),4.71(s ,2H),4.68-4.59(m,5H),4.55(d,J=11.9Hz,1H),4.44(dd,J=13.3,9.1Hz,2H),4.40(s ,2H),4.34-4.29(m,1H),4.26-4.15(m,4H),4.14-4.04(m,5H),4.02-3.90(m,4H),3.8 9-3.78(m,5H),3.70-3.64(m,3H),3.59(d,J=5.6Hz,2H),3.53-3.44(m,3H),3.24(t,J =6.8Hz,2H),3.06(dd,J=10.6,3.7Hz,1H),2.77(dd,J=15.2,6.2Hz,1H),2.44(dd,J=1 5.2,6.7Hz,1H),1.99(s,3H),1.80(s,1H),1.65-1.53(m,4H),1.44-1.37(m,2H),1.34 (d,J=2.9Hz,3H),1.28(d,J=5.9Hz,3H),1.09(d,J=6.4Hz,3H),1.00(d,J=6.4Hz,3H). 13C NMR (100MHz, CDCl3) δ171.6,170.4,163.7,161.9,161.2,138.8,138.7,138.6,138.51,138.47,137.0,136.0,128.60,128.56,128 .5,128.45,128.41,128.39,128.35,128.27,128.24,128.22,128.18,128.1,127.9,127.8,127.7,127.54,127.51,127.48,127.42 ,127.38,127.33,127.29,127.2,102.2,99.5,98.2,97.1,92.6,92.5,92.4,79.6,79.4,74.8,74.2,74.0,73.2,72.7,72.3,71.4,70.8,70.2,69.7,67.7,67.3,66.2,64.8,62.8,60.4,58.2,55.9,51.3,44.9,42.0,29.1,28.6,23.2,20.8,20.6,19.0,16.9,16.5.

[0258] Synthetic compound 2-1a

[0259]

[0260] The crude product 2-52a (50.8 mg, 0.0228 mmol) was dissolved in a mixed solution of 7 mL t-BuOH and 3 mL H2O. 200 mg Pd(OH)2 / C was added, and the mixture was purged with hydrogen three times in an ice bath. The reaction was carried out at room temperature for 5 days, and the solution was evaporated to dryness to obtain the crude product. The crude product was then dissolved in 1 mL of 1 M lithium hydroxide solution and reacted at room temperature for 3 h. The reaction was confirmed to be complete by TLC, and the mixture was separated by gel column chromatography (DCM / MeOH = 1:1) to obtain a white solid 2-1a (19.6 mg, 0.01778 mmol, 78%). 1H NMR(600MHz,D2O)δ5.36(d,J=15.8Hz,1H),5.17(s,1H),4.89-4.81(m,2H),4.47(d,J=7.7Hz ,1H),4.26-3.96(m,6H),3.93-3.81(m,3H),3.81-3.51(m,15H),3.35-3.24(m,2H),2.93-2. 83(m,2H),2.37(q,J=14.4Hz,2H),1.98(s,3H),1.95-1.86(m,6H),1.80(d,J=3.4Hz,2H),1. 63-1.48(m,4H),1.36-1.26(m,2H),1.27-1.16(m,6H),1.11-1.04(m,3H),1.04-0.93(m,3H). 13 C NMR(150MHz,D2O)δ180.3,175.6,174.5,173.5,101.6,100.5,99.9,98.8,97.9 ,80.5,79.8,78.4,76.8,74.1,73.7,73.5,72.9,71.8,71.7,70.1,69.8,69.4,6 7.9,67.0,66.9,66.2,66.0,61.5,59.9,56.5,53.1,52.2,51.3,44.3,39.3,28 .3,26.5,23.1,22.5,22.2,21.9,21.8,20.3,17.8,15.4.HRMS(ESI)Calculated for C 46 H 81 N5O 25 [M+H] + 1103.5221, found 1104.5293.

[0261] Synthesize compounds 2-52b and 2-1b

[0262] The synthesis of compound 2-52b differs from that of compound 2-52a in that compound 2-2a is replaced with 2-2b. Similarly, the synthesis of compound 2-1b differs from that of compound 2-1a in that compound 2-52a is replaced with 2-52b. The structures of the synthesized 2-52b and 2-1b are shown below:

[0263]

[0264] Example 2: Synthesis of zwitterionic polysaccharide PS A2 decansaccharide repeating unit compound

[0265] 1. Synthesize compounds 3-6 (including 3-6a and 3-6b).

[0266] Synthesize compound 3-6a

[0267]

[0268] First, compound 3-12a was synthesized using compound 2-51a as a starting material. The specific synthesis process is the same as the experimental process in Example 1 for synthesizing compound 2-49 using compound 2-48 as a starting material.

[0269]

[0270] Compound 3-12a (145.0 mg, 0.07 mmol) was dissolved in 3 mL of Acetone, cooled to 0 °C, and Cs₂CO₃ (48.3 mg, 0.15 mmol, 2 eq) and PTFAI (16.8 μL, 0.11 mmol, 1.5 eq) were added sequentially. The mixture was gradually restored to room temperature and reacted for 2 h. The reaction was confirmed to be complete by TLC. The mixture was then separated by concentrated column chromatography under reduced pressure (PE / EA = 10:1) to obtain a colorless viscous liquid 3-6a (135.4 mg, 0.05 mmol, 74%). 1 H NMR (400MHz, Acetone) δ7.43-7.22(m,27H),7.13(t,J=7.5Hz,1H),6.95(d,J= 7.8Hz,2H),6.41(s,1H),5.36(dd,J=5.7,2.1Hz,2H),5.27(d,J=3.9Hz,1H),5 .18(d,J=12.6Hz,1H),5.03(d,J=12.7Hz,1H),4.88(m,2H),4.73-4.67(m,2H) ,4.64(dd,J=11.8,5.9Hz,3H),4.58(m,1H),4.53(d,J=12.1Hz,1H),4.44(d,J =12.1Hz,1H),4.42-4.39(m,1H),4.39-4.24(m,6H),4.20-4.11(m,4H),4.05( m,5H),3.94-3.86(m,2H),3.81(dd,J=10.4,3.4Hz,1H),3.66(dd,J=10.4,7.3 Hz,1H),2.73(m,2H),2.56-2.49(m,3H),2.10(s,3H),1.99(s,3H),1.37(d,J= 6.1Hz, 3H), 1.34 (d, J = 6.0Hz, 3H), 1.18-1.09 (m, 21H), 1.00 (d, J = 6.4Hz, 3H). 13C NMR(101MHz,Acetone)δ205.51,205.41,171.67,170.97,169.84,162.39,162.32,162.13,162.06,161.26,1 61.17,143.63,139.09,139.01,138.97,137.85,136.69,128.82,128.47,128.41,128.38,128.16,128.13,1 28.09, 128.05, 128.01, 127.93, 127.86, 127.82, 127.80, 127.67, 127.58, 127.54, 127.40, 127.35, 127.31, 127.23, 127.17, 127.10, 127.04, 126.79, 124.37, 119.40, 99.64, 99.29, 98.19, 93.06, 92.83, 92.79, 80.02, 7 7.07,76.92,75.73,74.57,74.51,74.16,74.02,72.87,72.80,72.51,71.96,71.62,70.66,69.42,69.27,69.24,68.26,65.84,65.77,65.42,62.60,62.18,56.66,56.57,54.42,54.32,53.82,42.22,37.06,36.89,31. 76,29.80,29.63,29.57,29.50,29.48,29.44,29.38,29.19,28.99,28.80,28.74,28.61,28.42,27.54,26.87,22.45,22.08,20.56,20.37,19.93,18.20,17.83,17.79,17.75,17.67,17.61,15.98,13.51,12.71,12.61.

[0271] Synthetic compound 3-6b

[0272] The synthesis of compound 3-6b differs from that of compound 3-6a in that compound 2-51a is replaced with 2-51b, and compound 3-12a is replaced with 3-12b. The structural formulas of compounds 3-12b and 3-6b are shown below:

[0273]

[0274] 2. Synthesize compounds 3-5 (including 3-5a and 3-5b).

[0275] Synthetic compound 3-5a

[0276]

[0277] Compound 2-51a (270.3 mg, 0.11 mmol) was dissolved in a mixture of 1 mL THF and 1 mL Py. HF / Py (0.1 mL) was added at 0 °C, and the reaction was carried out at 40 °C for 48 h. The reaction was confirmed to be complete by TLC. NaHCO3 solid was added to quench the reaction, and the mixture was filtered and evaporated to dryness. The mixture was separated by column chromatography (PE / EA = 3:1) to give a colorless liquid 3-5 (211.5 mg, 0.10 mmol, 84%). 1 H NMR (400MHz, CDCl3) δ7.55(d,J=8.8Hz,1H),7.28(m,29H),6.69(d,J=8.9Hz,2H),5.17-5.05(m,4H),4.99(dd,J=10.0,7.5Hz,1H),4.93 -4.84(m,2H),4.69-4.53(m,5H),4.51-4.38(m,5H),4.34(dd,J=7.5,3.5Hz,1H),4.28-4.15(m,5H),4.09(m,6H),4.00-3.88(m,4H),3.8 8-3.74(m,5H),3.70(dd,J=10.4,4.3Hz,1H),3.59-3.42(m,5H),3.26(t,J=6.8Hz,2H),3.07(dd,J=10.6,3.7Hz,1H),2.79(dd,J=15.1, 6.7Hz,1H),2.67(m,2H),2.51(m,4H),2.12(s,3H),2.00(s,3H),1.59(m,4H),1.39(m,5H),1.28(d,J=6.0Hz,3H),0.99(d,J=6.6Hz,3H). 13CNMR(101MHz,CDCl3)δ206.14,171.92,171.78,170.50,163.66,162.19,161 .18,138.71,138.51,138.42,136.86,135.93,128.63,128.59,128.41,128.3 8, 128.34, 128.28, 128.21, 128.14, 128.03, 127.93, 127.64, 127.56, 127.51, 127.48, 127.45, 127.29, 100.50, 99.56, 97.32, 92.60, 92.55, 92.40, 79.19, 77.42,77.30,77.10,76.93,76.79,76.29,74.97,74.27,74.22,73.25,72.77,72.23,71.61,71.21,71.12,70.30,69.45,67.58,66.31,64.81,62.62,60. 30,57.42,55.97,54.14,51.36,45.01,42.24,37.74,37.71,32.26,29.80,29.02,28.58,27.80,23.38,23.19,20.81,20.75,20.36,18.73,16.52,12.84.

[0278] Synthetic compound 3-5a

[0279] The synthesis of compound 3-5b differs from that of compound 3-5a in that compound 2-51a is replaced with 2-51b. The structural formula of compound 3-5b is shown below:

[0280]

[0281] 3. Synthesize compounds 3-4 (including 3-4a and 3-4b).

[0282] Synthetic compound 3-4a

[0283]

[0284] Compounds 3-6a (200.0 mg, 0.08 mmol) and 3-5a (130.0 mg, 0.06 mmol) were dissolved in 1 mL of DCM ( MS drying and dehydration), add freshly activated MS, cooled to -20℃ and stirred for 10 min, then added TBSOTf (3.0 μL, 0.013 mmol, 0.3 eq), reacted at -20℃ for 4 h, and the reaction was confirmed to be complete by TLC. The reaction was quenched by adding TEA, and separated by concentrated column chromatography (PE / EA = 3:1) to obtain colorless liquid 3-4a (153.9 mg, 0.04 mmol, 55%). 1 H NMR (600MHz, CDCl3) δ7.33-7.17(m,50H),6.67(d,J=9.6Hz,3H),6.58(d,J=9.4Hz,1H),5.18-4.95( m,12H),4.87(dd,J=11.1,6.6Hz,2H),4.80(d,J=11.9Hz,1H),4.68-4.55(m,9H),4.49-4.46(m,2H) ,4.45(d,J=3.7Hz,2H),4.43(d,J=3.0Hz,1H),4.40(d,J=6.1Hz,1H),4.38-4.31(m,5H),4.27-4.23 (m,2H),4.23-4.14(m,8H),4.12-3.97(m,9H),3.93(m,4H),3.87-3.78(m,6H),3.76(t,J=9.1Hz,1H) ,3.74-3.69(m,2H),3.67(dd,J=10.4,3.9Hz,1H),3.56(m,1H),3.51(m,2H),3.48-3.41(m,4H),3.2 6(t,J=6.9Hz,3H),3.18(dd,J=10.3,4.0Hz,1H),2.78(m,2H),2.69-2.63(m,3H),2.62-2.41(m,7H), 2.12(s,3H),2.09(s,3H),2.01(d,J=8.1Hz,6H),1.60(m,4H),1.45-1.39(m,2H),1.37(d,J=6.1Hz, 3H), 1.32 (dd, J=13.1, 6.5Hz, 6H), 1.21 (d, J=6.1Hz, 3H), 1.09 (t, J=7.6Hz, 21H), 1.01-0.95 (m, 6H). 13C NMR (151MHz, CDCl3) δ206.21,206.01,171.89,171.84,171.62,170.65,170.43,162.45,162.28,162.14,162.10,161.16,138 .69,138.56,138.38,138.35,138.33,138.23,136.88,136.78,135.87,130.92,128.84,128.69,128.64,128.61,128.58,128 .48,128.41,128.37,128.31,128.25,128.21,128.19,128.17,128.11,128.08,128.01,127.99,127.64,127.60,127.56,127.52,127.46,127.40,127.38,127.32,127.21,100.56,100.41,99.31,98.83,97.29,96.50,92.78,92.55,92.49,92.36,79.59 ,79.28,77.24,77.03,76.82,76.06,75.48,74.96,74.76,74.37,74.14,73.25,73.16,72.88,72.82,72.30,72.23,72.04,71.52,71.39,71.25,71.01,70.42,69.41,68.10,66.29,66.25,65.87,65.57,65.45,62.54,62.49,60.41,59.83,57.42,57.08 ,56.28,55.20,54.08,51.34,42.60,42.18,37.72,37.67,31.44,30.57,30.19,29.78,29.32,29.01,28.57,27.75,27.62,23.18,20.86,20.78,20.55,20.17,19.18,18.70,18.34,18.20,18.09,17.95,16.46,16.39,14.20,13.73,13.02,12.82,12.62.

[0285] Synthetic compound 3-4b

[0286] The synthesis of compound 3-4b differs from that of compound 3-4a in that compound 3-6a is replaced with 3-6b, and compound 3-5a is replaced with 3-5b. The structural formula of compound 3-4b is shown below:

[0287]

[0288] 4. Synthesize compounds 3-3 (including 3-3a and 3-3b).

[0289] Synthesize compound 3-3a

[0290]

[0291] Compound 3-4a (140.6 mg, 0.04 mmol) was dissolved in a mixed solution of 0.2 mL AcOH and 0.8 mL Py. 80% hydrazine hydrate (3.5 μL, 0.08 mmol, 2 eq) was added at 0 °C, and the reaction was carried out at room temperature for 35 min. The reaction was confirmed to be complete by TLC. The solution was diluted with EA, washed with water, NaHCO3, and saturated NaCl, dried over anhydrous Na2SO4, filtered, and evaporated to dryness. The solution was then separated by column chromatography (PE / EA = 4:1) to give a white solid 3-3a (118.2 mg, 0.03 mmol, 89%). 1 H NMR (600MHz, CDCl3) δ7.34-7.18(m,51H),6.73-6.60(m,4H),5.12-4.97(m,9H),4.85(dd,J=23.6,11.0Hz,2H),4.72-4.55(m,8H),4. 51-4.41(m,5H),4.40-4.30(m,6H),4.24(m,5H),4.21-4.14(m,4H),4.13-4.03(m,6H),3.98(dt,J=18.1,6.5Hz,3H),3.94-3.86(m,5H ),3.85-3.78(m,4H),3.74-3.65(m,3H),3.60(m,2H),3.54-3.49(m,3H),3.26(t,J=6.8Hz,2H),3.14(m,2H),2.78(m,2H),2.46(m,2H) ,1.99-1.92(m,6H),1.60(m,4H),1.47-1.40(m,2H),1.38-1.29(m,9H),1.24(d,J=6.4Hz,3H),1.19-1.05(m,21H),1.00-0.94(m,6H). 13C NMR (151MHz, CDCl3) δ172.04,170.35,162.52,162.44,162.06,161.18,161.07,138.44,138.2 9,138.06,136.74,135.82,128.60,128.57,128.55,128.52,128.49,128.36,128.31,128.27,1 28.25, 128.23, 128.18, 128.16, 128.09, 128.06, 127.86, 127.63, 127.60, 127.53, 127.51, 127.48, 127.44, 127.43, 127.40, 127.26, 103.08, 102.71, 100.08, 99.53, 99.18, 97.72, 97.50, 92.7 9,92.66,92.44,79.55,77.90,77.24,77.03,76.82,74.55,74.30,74.16,73.45,73.26,73.03,72.41,72.16,71.50,71.31,70.61,70.36,69.85,69.39,68.07,66.41,65.77,65.38,62.50,59 .79,59.38,58.09,56.29,55.20,54.60,51.30,51.29,50.85,42.53,42.00,29.14,29.10,28.57,23.25,23.23,23.21,21.03,20.75,19.15,18.71,18.18,18.05,16.47,16.45,16.30,12.80.

[0292] Synthetic compound 3-3b

[0293] The synthesis of compound 3-3b differs from that of compound 3-3a in that compound 3-4a is replaced with 3-4b. The structural formula of compound 3-3b is shown below:

[0294]

[0295] 5. Synthesize compounds 3-2 (including 3-2a and 3-2b).

[0296] Synthesize compound 3-2a

[0297]

[0298] Compounds 3-3a (190.0 mg, 0.054 mmol) and 2-4 (132.8 mg, 0.021 mmol, 4 eq) were dissolved in 1 mL of LDC ( MS drying and dehydration), add freshly activated MS, cooled to -20℃ and stirred for 10 min, then TfOH (3.7 μL, 0.016 mmol, 0.3 eq) was added, and the reaction was carried out at -20℃ for 4 h. The reaction was confirmed to be complete by TLC. The reaction was quenched by adding TEA, and separated by concentrated column chromatography (PE / EA = 3:1) to obtain colorless liquid 3-2a (138.0 mg, 0.030 mmol, 57%). 1 H NMR (600MHz, CDCl3) δ7.35-7.25(m,55H),7.24-7.16(m,32H),6.66(m,2H),5.21-5 .17(m,1H),5.14(d,J=4.0Hz,1H),5.10(m,1H),5.06(m,1H),5.01(m,4H),4.97(d,J =7.4Hz,2H),4.92(m,4H),4.89-4.85(m,2H),4.81(d,J=6.6Hz,2H),4.78(t,J=6.1H z,1H),4.75(d,J=11.6Hz,2H),4.72-4.59(m,16H),4.55(m,4H),4.50-4.39(m,7H), 4.38-4.29(m,5H),4.23(m,11H),4.17-4.10(m,5H),4.10-3.95(m,12H),3.91(m,5H ),3.88-3.78(m,8H),3.65(m,4.4Hz,8H),3.54(m,4H),3.46(m,5H),3.24(m,2H),3. 14(dd,J=10.3,4.1Hz,1H),2.79(m,2H),2.41(m,2H),2.02-1.95(m,6H),1.59(m,4H ),1.46-1.40(m,2H),1.32(m,9H),1.24(d,J=6.1Hz,3H),1.08m,27H),1.00(m,6H). 13C NMR (151MHz, CDCl3) δ171.40,171.28,170.50,170.34,167.72,162.44,162.26,161.88,161.18,138.73,138.64,138.56,138.48,138.38 ,138.21,137.10,136.91,136.00,135.94,132.31,130.91,128.84,1 28.57,128.53,128.47,128.44,128.39,128.35,128.29,128.24,128 .21,128.19,128.17,128.14,128.11,128.06,128.03,127.97,127.95,127.88,127.83,127.64,127.59,127.54,127.51,127.48,127.44,127.40,127.38,127.30,127.28,127.25,127.21,127.15,126.97,102.09,100.19,99.06,98.21,98.16,97.20,92.82,92.76,92.61,92.4 1,79.56,79.51,77.25,77.04,76.82,76.42,74.81,74.73,74.50,74.36,74.22,74.03,73.95,73.19,73.11,73.02,72.83,72.68,72.60,72.29,71.86,71.61,71.02,70.71,70.29,69.64,68.04,67.59,67.26,66.08,65.98,65.79,65.57,65.51,65.33,62.66,62.50,59.47,58 .27,57.42,56.33,55.68,51.29,44.88,42.26,41.86,32.27,31.51,31.44,30.57,30.19,30.14,29.69,29.31,29.09,28.57,27.21,23.40,23.22,20.92,20.80,20.76,20.66,19.18,19.01,18.57,18.19,18.06,16.90,16.83,16.55,16.33,14.12,13.73,13.01,12.81,12.61.

[0299] Synthetic compound 3-2b

[0300] The synthesis of compound 3-2b differs from that of compound 3-2a in that compound 3-3a is replaced with 3-3b. The structural formula of compound 3-2b is shown below:

[0301]

[0302] 6. Synthesize compound 3-1 (including 3-1a and 3-1b).

[0303] Synthetic compound 3-1a

[0304]

[0305] The crude product 3-2a (75 mg, 0.017 mmol) was dissolved in a mixed solvent of 1 mL Py and 3 mL THF. HF / Py (0.1 mL) was added at 0 °C, and the reaction was carried out at 40 °C for 48 h. TLC confirmed the reaction was complete. NaHCO3 solid was added to quench the reaction. The mixture was filtered, evaporated to dryness, and separated by column chromatography (PE / EA = 3:1). Vacuum distillation under reduced pressure yielded a colorless viscous liquid. 100 mg Pd(OH)2 / C was added to a mixed solution of 7 mL t-BuOH and 3 mL H2O of the obtained crude product. Hydrogen was replaced three times in an ice bath, and the mixture was reacted with hydrogen at room temperature for 5 days. Evaporation yielded the crude product. The crude product was dissolved in 1 mL of 1 M lithium hydroxide solution and reacted at room temperature for 3 h. TLC confirmed the reaction was complete. Gel column chromatography (H2O / MeOH = 1:1) yielded a white solid 3-1a (16 mg, 0.011 mmol, 63%). 11H NMR (600 MHz, D2O) δ 5.33 - 5.25 (m, 2H), 5.18 - 5.11 (m, 2H), 4.96 (d, J = 3.5 Hz, 1H), 4.85 (m, 1H), 4.80 (m, 2H), 4.58 (d, J = 8.0 Hz, 1H), 4.44 (d, J = 4.8 Hz, 1H), 4.43 (d, J = 7.8 Hz, 1H), 4.21 - 4.02 (m, 11H), 3.97 (s, 1H), 3.92 (d, J = 10.5 Hz, 1H), 3.83 (q, J = 9.9 Hz, 5H), 3.77 (s, 2H), 3.73 - 3.50 (m, 28H), 3.47 (d, J = 7.5 Hz, 2H), 3.31 - 3.22 (m, 4H), 2.84 (t, J = 7.6 Hz, 2H), 2.40 (s, 4H), 1.95 (s, 3H), 1.93 (s, 3H), 1.90 - 1.83 (m, 11H), 1.52 (m, 4H), 1.30 - 1.24 (m, 2H), 1.24 - 1.14 (m, 12H), 1.05 (d, J = 6.5 Hz, 3H), 1.03 (d, J = 6.5 Hz, 3H), 0.98 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.4 Hz, 3H). 13 13C NMR (151 MHz, D2O) δ 175.68, 174.67, 174.65, 174.46, 173.52, 173.48, 103.80, 101.61, 100.66, 100.40, 99.86, 99.50, 99.15, 99.08, 97.78, 80.92, 80.31, 80.15, 79.83, 79.05, 78.48, 76.79, 74.28, 74.15, 73.65, 73.50, 72.93, 72.90, 71.86, 71.79, 71.73, 70.08, 69.79, 69.41, 68.90, 68.49, 68.14, 67.90, 66.97, 66.81, 66.75, 66.47, 66.17, 65.91, 61.93, 61.50, 59.95, 56.49, 55.10, 53.07, 52.28, 51.31, 50.47, 39.33, 28.36, 26.46, 26.36, 22.67, 22.49, 22.20, 22.02, 21.92, 21.88, 21.76, 20.47, 20.38, 17.95, 17.92, 17.79, 17.73, 15.67, 15.47, 15.44, 15.40.[[ID=?]] [[ID=?]]

[0306] Synthesize compound 3 - 1b[[ID=?]]

[0307] The synthesis of compound 3-1b differs from that of compound 3-1a in that compound 3-2a is replaced with 3-2b. The structural formula of compound 3-1b is shown below:

[0308]

[0309] The abbreviations in the above embodiments are as follows: Ac is acetyl, Ac2O is acetic anhydride, AcOH is glacial acetic acid, aq is aqueous solution, All is allyl, BAIB is iodophenyl diacetic acid, Bn is benzyl, brs is a broad singlet, Bu2SnO is dibutyltin oxide, Bz is benzoyl, CSA is camphor sulfonic acid, DCM is dichloromethane, DBU is 1,8-diazobisspirocyclic [5.4.0]undec-7-ene, dd is a doublet, DDQ is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, DTT is... Dithiothreitol, DIPEA is diisopropylethylamine, DMAP is 4,4-dimethylaminopyridine, DMF is dimethylformamide, DTBMP is 2,6-di-tert-butyl-4-methylpyridine, EA is ethyl acetate, EDCI is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, eq is equivalent, iPr is isopropyl, m is multiplet, M is moles per liter, Me is methyl, mg is milligram, min is minute, mL is milliliters, mmol is millimole, mol is mole, Mp is p-methoxyphenyl, Ms is minute. Sub-sieve or mass spectrometry, Nap is 2-(bromomethyl)naphthalene, NBS is N-bromosuccinimide, NMR is nuclear magnetic resonance, PE is petroleum ether, ppm is parts per million, Py is pyridine, rt is room temperature, s is singlet, t is triplet or time, TMS is trimethylsilyl, TMSOTf is trimethylsilyl trifluoromethanesulfonate, TBAN3 is tetrabutylammonium azide, t-Bu is tert-butyl, TBAF is tetrabutylammonium fluoride, TBDPS is tert-butyldiphenylsilyl, TBS is tert-butyldimethylsilyl, TBSOTf is tert-butyl Dimethylsilyl trifluoromethanesulfonate, TEMPO is 2,2,6,6-tetramethylpiperidine oxide, Tf is trifluoromethanesulfonate, TIPS is triisopropylsilyl, TEA is triethylamine, TFA is trifluoroacetic acid, THF is tetrahydrofuran, TLC is thin-layer chromatography, TolSH is p-toluenethiophenol, Ts is p-toluenesulfonyl, TsOH is p-toluenesulfonic acid, Toluene is toluene, Cp2TiCl2 is dichlorodicyclopentadiene, NIS is N-iodosuccinimide, PTFAI is trifluoroacetylimide, and CAN is cerium ammonium nitrate.

[0310] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound, characterized in that, Including the following structural formulas:

2. A method for synthesizing the zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound according to claim 1, characterized in that, Includes the following steps: S1, using compounds 2-7 and 2-8 in a molar ratio of 1:1.1 to 1.3 as raw materials, obtained compound 2-5 through glycosylation and deprotection reactions; S2, using compounds 2-9 and 2-10 in a molar ratio of 1.3 to 1.5:1 as raw materials, yielded compound 2-6 through glycosylation and deprotection reactions; S3, using compounds 2-5 and 2-6 in a molar ratio of 1.1 to 1.3:1 as raw materials, undergoes glycosylation and deprotection reactions to obtain compound 2-3; S4, using compounds 2-3 and 2-4 in a molar ratio of 1:1.9 to 2.2 as raw materials, glycosylation reaction yields compound 2-2; S5, the compound 2-2 was deprotected to obtain the zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound 2-1; PG1 to PG7 are protecting groups, each independently selected from Bn, TCA, TIPS, Ac, (CH2)5N3, Lev or Mp, where Bn is benzyl, TCA is trichloroacetyl, TIPS is triisopropylsilyl, Ac is acetyl, Lev is acetylacetyl, and Mp is p-methoxyphenyl.

3. The method for synthesizing the zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound as described in claim 2, characterized in that, Compound 2-7 in S1 includes 2-7a or 2-7b, and the synthesis process of 2-7a and 2-7b includes the following steps: S1-1, using compound 2-12 as the starting material, compounds 2-14a and 2-14b are synthesized through the following steps S1-11 and S1-12: S1-11, the C6 position of compound 2-12 is oxidized by a two-step reaction of Swern oxidation and Wittig to obtain compound 2-13; S1-12, K2OsO4·2H2O, K3Fe(CN)6 and K2CO3 are dissolved in a mixed solvent of t-BuOH and H2O in a volume ratio of 1:0.9 to 1.1, and compound 2-13 is added to the mixed solvent at 0°C to react and obtain compounds 2-14a and 2-14b; the molar ratio of K2OsO4·2H2O, K3Fe(CN)6 and K2CO3 to compound 2-13 is 1:59 to 61:65 to 67:19 to 21; S1-2, using compound 2-14b as the starting material, compounds 2-18a and 2-18b are synthesized through the following steps S1-21, S1-22, S1-23 and S1-24: S1-21, hydroxyl protection of C7 of compound 2-14b yields compound 2-15; S1-22, esterification of the C6 hydroxyl group of compound 2-15 to obtain compound 2-16; S1-23, under the action of CpTi(Me)2, the ester group in compound 2-16 is converted into an olefin to obtain compound 2-17; S1-24, compound 2-17 is hydrogenated with Pd(OH)2 / C to reduce the double bond to methyl, yielding compounds 2-18a and 2-18b; S1-3, using compound 2-18a as the starting material, compound 2-7a is synthesized through the following steps S1-31, S1-32 and S1-33: S1-31, the carboxyl group in compound 2-18a is esterified to obtain compound 2-21; S1-32, compound 2-21 is obtained by removing the ketal from compound 2-21 to give compound 2-22; S1-33, hydroxyl protection is performed at the C3 position of compound 2-22 to obtain compound 2-7a; or, S1-3, using compound 2-18b as the starting material, compound 2-7b is synthesized through the following steps S1-31, S1-32 and S1-33: S1-31, the carboxyl group in compound 2-18b is esterified to obtain compound 2-53; S1-32, compound 2-53 was deketed to obtain compound 2-54; S1-33, hydroxyl protection is performed at the C3 position of compound 2-54 to obtain compound 2-7b; 4. The method for synthesizing the zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound as described in claim 2, characterized in that, The synthesis of compounds 2-8 described in S1 includes the following steps: S1-4, using compound 2-27 as a raw material, wherein the two hydroxyl groups on C2 and C4 of compound 2-27 are subjected to an upper protecting group, azide inversion, amino inversion and amino protection to obtain compound 2-28; S1-5, compound 2-28 is desulfurized to obtain compound 2-29; compound 2-29 undergoes a glycosylation reaction with PTFAI under Cs2CO3 conditions to obtain compound 2-8; 5. The method for synthesizing the zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound as described in claim 2, characterized in that, The synthesis method of compound 2-5 in S1 is as follows: using compounds 2-7 and 2-8 in a molar ratio of 1.1 to 1.3:1 as raw materials, compound 2-48 is obtained by glycosylation reaction; after removing the PG7 protecting group from compound 2-48, compound 2-49 is obtained; compound 2-49 is glycosylated with PTFAI under Cs2CO3 conditions to obtain compound 2-5.

6. The method for synthesizing the zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound as described in claim 2, characterized in that, The synthesis of compounds 2-6 described in S2 includes the following steps: S2-1, using compound 2-9 and compound 2-10 in a molar ratio of 1.3 to 1.5:1 as raw materials, glycosylation reaction yields compound 2-50; S2-2, Compound 2-50 was deprotected by the PG5 protecting group to obtain compound 2-6; 7. The method for synthesizing the zwitterionic polysaccharide PS A2 pentasaccharide repeating unit compound as described in claim 2, characterized in that, The synthesis of compounds 2-3 described in S3 includes the following steps: S3-1, using compound 2-5 and compound 2-6 in a molar ratio of 1.1 to 1.3:1 as raw materials, compound 2-51 was obtained by glycosylation reaction; S3-2, Compound 2-51 was deprotected by the PG6 protecting group to obtain compound 2-3; 8. A zwitterionic polysaccharide PS A2 decansaccharide repeating unit compound, characterized in that, Including the following structural formulas:

9. A method for synthesizing the zwitterionic polysaccharide PS A2 decasaccharide repeating unit compound according to claim 8, characterized in that, Includes the following steps: (1) Using compounds 3-6 and 3-5 in a molar ratio of 2 to 2.1:1 as raw materials, compound 3-4 was obtained by glycosylation reaction; (2) Compound 3-4 was deprotected by the PG6 protecting group to obtain compound 3-3; (3) Compound 3-3 and a monosaccharide compound in a molar ratio of 2.5 to 2.7:1 were used as raw materials and subjected to a glycosylation reaction to obtain compound 3-2; (4) After hydrogenation and removal of the protecting group, compound 3-2 is obtained as decansaccharide repeating unit compound 3-1; 10. The method for synthesizing the zwitterionic polysaccharide PS A2 decasaccharide repeating unit compound as described in claim 9, characterized in that, The synthesis process of compounds 3-6 is as follows: compound 2-51 is deprotected by the PG5 protecting group to obtain compound 3-12; compound 3-12 undergoes a glycosylation reaction with PTFAI under Cs2CO3 conditions to obtain compound 3-6; Compound 3-5 was prepared by removing the PG3 protecting group from compound 2-51 as a raw material.

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