Chemical Synthesis of an Octasaccharide Derivative Related to Group B Streptococcus Cell-Wall Polysaccharide

Group B Streptococcus (GBS) is the major pathogen that causes invasive infectious diseases in neonates and infants. The development of preventive and therapeutic strategies against GBS infection has been becoming the most pressing subject worldwide. Group B carbohydrate (GBC), the group B-specific polysaccharide that distinguishes GBS with other streptococci species, has been identified as an attractive antigen for diagnosis and vaccine development because of its highly conservative tetra-antennary structure. In this paper, a highly convergent [3 + 5] glycosylation strategy for efficient synthesis of an octasaccharide derivative related to GBC oligosaccharide unit II has been developed. In this synthesis, each glycosylation reaction was efficiently constructed with glycosyl imidates, especially trifluoroacetimidate, as donors, and each glycosidic bond was stereoselectively controlled via the neighboring group participation effect of acyl group on the 2-O-position of imidate donors or the solvent effect of Et₂O. Furthermore, the aminoethylphosphate group was smoothly installed on the 6-O-position of d -glucitol residue using the phosphoramidite method. After global deprotection, the target octasaccharide was successfully obtained from d -glucitol in 29 steps with an overall yield of 1.37%. The free amino group installed on the aminoethylphosphate spacer of the target molecule enables its modification with functionalized biomolecules for further biological studies.      

Synthetic directions towards capsular polysaccharide of Streptococcus pneumoniae serotype 18C

An efficient synthetic strategy has been developed for the synthesis of the tri, tetrasaccharide block and pentasaccharide corresponding to the capsular polysaccharide of Streptococcus pneumonia serotype 18C as their 2-aminoethyl glycosides. A one-pot glycosylation-deprotection, sequential glycosylations strategy has been adopted for the construction of the fragments and pentasaccharide derivative, which were then transformed into target compound after a series of functional group transformations. The synthetic method relies on the use of p-methoxybenzyl ether as an in situ-removable protecting group to reduce the number of reaction steps significantly. Here H₂SO₄-silica has been used successfully as a promoter for all glycosylation reaction. In addition, the synthetic target also contained a free amino group at its reducing end, facilitating its conjugation with other molecules for various biological studies and applications.     

A Concise Synthesis of a BODIPY-Labeled Tetrasaccharide Related to the Antitumor PI-88

A convergent synthetic route to a tetrasaccharide related to PI-88, which allows the incorporation of a fluorescent BODIPY-label at the reducing-end, has been developed. The strategy, which features the use of 1,2-methyl orthoesters (MeOEs) as glycosyl donors, illustrates the usefulness of suitably-designed BODIPY dyes as glycosyl labels in synthetic strategies towards fluorescently-tagged oligosaccharides.     

Synthesis of a Trisaccharide Related to the Cytotoxic Triterpenoid Saponins Isolated from the Bark of Albizia procera

Chemical synthesis of a trisaccharide related to the cytotoxic triterpenoid saponins isolated from the bark of Albizia procera has been accomplished through a concise stepwise glycosylation strategy starting from commercially available D ‐xylose, 2‐acetamido‐2‐deoxy‐D ‐glucose and L ‐arabinose. The target trisaccharide was designed with a 4‐methoxyphenyl (MP) aglycone to extend the scope of conversion to suitable glycoconjugates via selective removal of 4‐methoxyphenyl (MP) group. An unexpected phenomenon, i.e., the arabinosyl residue assumed the ¹C₄ conformation instead of the typical ⁴C₁ form, was observed. Deprotection could restore the normal conformation.     

Stereoselective Synthesis of the O-antigen of A. baumannii ATCC 17961 Using Long-Range Levulinoyl Group Participation

Herein, we described the first synthesis of the pentasaccharide and decasaccharide of the A. baumannii ATCC 17961 O-antigen for developing a synthetic carbohydrate-based vaccine against A. baumannii infection. The efficient synthesis of the rare sugar 2,3-diacetamido-glucuronate was achieved using our recently introduced organocatalytic glycosylation method. We found, for the first time, that long-range levulinoyl group participation via a hydrogen bond can result in a significantly improved β-selectivity in glycosylations. This solves the stereoselectivity problem of highly branched galactose acceptors. The proposed mechanism was supported by control experiments and DFT computations. Benefiting from the long-range levulinoyl group participation strategy, the pentasaccharide donor and acceptor were obtained via an efficient [2+1+2] one-pot glycosylation method and were used for the target decasaccharide synthesis.     

与癌症相关的糖类抗原Globo-H六糖的全合成进展

Globo-H作为一种和乳腺癌、前列腺癌相关的复杂糖类抗原,其发现为糖类疫苗开发和癌症免疫治疗带来了机遇,但如何高效、高纯地获得合成糖类抗原,以供研究和临床应用,也向寡糖合成方法学提出了挑战.综述了1995年Danishefsky首次以糖烯组装策略全合成Globo-H以来的各种新方法,如:Schmidt的三氯乙酰亚胺酯法、Boons的双向糖苷化法、Wong的基于糖基给体活性差异的一锅煮策略、Seeberger的液相线性合成和固相自动组装法、Huang的多组份反复预活化一锅煮法和最新报道的酶法.就糖合成方法学而言,硫苷法依旧可称为"明星方法",糖烯、三氯乙酰亚胺酯和氟代糖也普遍采用,磷酸酯糖基给体在固相合成中的应用正显示出其新的活力.这些方法代表了当今糖化学的水平和发展趋势.     

Stereoselective Synthesis of the Hexasaccharide Repeating Unit of the Cell Wall Polysaccharide from Kineosporia aurantiaca VKM Ac-720T Employing the Direct Glycosylation with Anomeric Hydroxy Sugars Involving Glycosyl Phthalate Intermediates

Synthesis of a suitably protected form of the hexasaccharide repeating unit of the cell wall polymer from Kineosporia aurantiaca VKM Ac-720 ^T has been achieved by the stereoselective direct glycosylation of a trisaccharide acceptor with a trisaccharide donor having an anomeric hydroxy group involving a glycosyl phthalate intermediate. Both the trisaccharide acceptor and the trisaccharide donor were obtained from a common trisaccharide, of which two β-mannopyranosyl linkages were constructed stereoselectively by employing the direct glycosylation method with the anomeric hydroxy sugar involving a glycosyl phthalate intermediate and the 2′-carboxybenzyl glycoside method, respectively.     

Chemical Synthesis Elucidates the Immunological Importance of a Pyruvate Modification in the Capsular Polysaccharide of Streptococcus pneumoniae Serotype 4

Carbohydrate modifications are believed to strongly affect the immunogenicity of glycans. Capsular polysaccharides (CPS) from bacterial pathogens are frequently equipped with a pyruvate that can be placed across the 4,6‐, 3,4‐, or 2,3‐positions. A trans‐2,3‐linked pyruvate is present on the CPS of the Gram‐positive bacterium Streptococcus pneumoniae serotype 4 (ST4), a pathogen responsible for pneumococcal infections. To assess the immunological importance of this modification within the CPS repeating unit, the first total synthesis of the glycan was carried out. Glycan microarrays containing a series of synthetic antigens demonstrated how antibodies raised against natural ST4 CPS specifically recognize the pyruvate within the context of the tetrasaccharide repeating unit. The pyruvate modification is a key motif for designing minimal synthetic carbohydrate vaccines for ST4.     

A Concise Approach to the Synthesis of L-and D-Deoxyribose

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Synthesis of a Tetra- and a Hexasaccharide Donor Corresponding to the Non-Reducing Termini of Mycobacterial 3-O-Methylmannose Polysaccharide (MMP)

Abstract

The blockwise synthesis of the title compounds, namely the tetra- and the hexasaccharide trichloroacetimidates (20) and (23), is described. Both acetates and imidates were employed as glycosyl donors in most of the coupling reactions. As nearly all of the synthetic intermediates contain one or more OCH₃ groups, they are easily identified by NMR spectroscopy the methyl signals. The fully functionalized compounds 20 and 23 correspond to the non-reducing terminal fragments of mycobacterial 3-O-methylmannose polysaccharide (MMP), and can serve as suitable building blocks for the synthesis of higher-order structures of MMP.     

The visualisation of the targeting of phospholipid liposomes to bacteria

Anionic and cationic phospholipid liposomes have been prepared from dipalmitoylphosphatidylcholine (DPPC) — phosphatidylinositol (PI) and DPPC-cholesterol-stearylamine (SA) mixtures over a range of composition and targeted to biofilms of the skin-associated bacterium Staphylococcus epidermidis to establish the optimum PI and SA content for targeting. The interaction of liposomes of optimum composition with the bacteria were visualized by electron microscopy using negative staining with uranyl acetate and phosphotungstic acid. It has been demonstrated that the liposomes absorb extensively to the bacterial surface. Immunoliposomes have been prepared with a covalently linked monoclonal antibody raised to antigenic determinants on the surface of the oral bacterium Streptococcus oralis. The targeting of the immunoliposomes to this bacterium has been visualized using a second gold labelled anti-antibody. As for the anionic and cationic liposomes the immunoliposomes adsorb to the surface of the bacteria. The results add support to the concept of using liposomes for the delivery of bactericides or therapeutic agents to bacteria.     

Synthesis of a Lipodisaccharidic Reagent for the Chemical Modification of Enzymes

ABSTRACT

The preparation of an amphiphilic lipodigalactosyl hemiacetal is described. Use of benzoyl protecting groups and mild conditions for detritylation allow preparation of a 1-α-C-allyl galactosyl acceptor without intramolecular acyl transfer. Condensation with a lipogalactosyl donor and cleavage of the protecting groups gave a C-allyl disaccharide. Reductive ozonolysis of the double bond yielded an aldehyde which spontaneously formed a cyclic hemiacetal with the C-2 hydroxyl group. In the Lewis acid catalyzed allylation of the penta-O-acetyl galactose with allyltrimethylsilane, the reactivity of the β-anomer is much higher than that of the α-anomer.     

A Concise Route to a Key Intermediate in the Total Synthesis of Sempervirine1

Enantiopure γ-amino and γ-hydroxy-β-ketosulfones have been synthesized in high yields from α-diazoketones derived from the α-amino and α-hydroxy acid chiral pools.     

Synthesis and antitumor activity of a group of diosgenyl glycosides

Using orthogonal protection-deprotection glycosylation strategy, a series of diosgenyl glycosides with same of monosaccharides component but different in sequence were synthesized. The antitumor activity in vitro of synthesized diosgenyl glycosides was evaluated by standard MTT assay. It was observed that diosgenyl glycosides with a rhamnopyranosyl at C2′ of glucopyranosyl residue show potent antitumor activity in vitro.     

Development of a chemiluminescent optical fiber immunosensor to detect Streptococcus pneumoniae antipolysaccharide antibodies

A chemiluminescent-based optical fiber immunosensor was developed for the detection of antipneumococcal antibodies. This was accomplished by developing a different chemical procedure utilizing 3-aminopropyl trimethoxysilane and cyanuric chloride to conjugate pneumococcal cell wall polysaccharides to the optical fiber tips, and by improving the sensitivity of the photodetection system. The lowest titer of antipneumococcal antibodies detected by the optical fiber was at a 1:819,200 dilution. The lowest corresponding value by standard enzyme-linked immunosorbent assay was at a 1:98,415 dilution. It was concluded that the optical immunosensor system is an accurate and sensitive method to detect antipneumococcal antibodies and may be an adequate tool to monitor antibodies in specimens such as saliva and urine.