Synthesis of Disaccharide Nucleosides by the O‐Glycosylation of Natural Nucleosides with Thioglycoside Donors

Disaccharide nucleosides constitute an important group of naturally‐occurring sugar derivatives. In this study, we report on the synthesis of disaccharide nucleosides by the direct O‐glycosylation of nucleoside acceptors, such as adenosine, guanosine, thymidine, and cytidine, with glycosyl donors. Among the glycosyl donors tested, thioglycosides were found to give the corresponding disaccharide nucleosides in moderate to high chemical yields with the above nucleoside acceptors using p‐toluenesulfenyl chloride (TolSCl) and silver triflate (AgOTf) as promoters. The interaction of these promoters with nucleoside acceptors was examined by ¹H NMR spectroscopic experiments.     

β-Kdo乙硫苷供体的合成

以草酰乙酸和D-阿拉伯糖为原料,经缩合-脱羧,乙酰化,甲酯化和乙硫苷化等4步反应合成了β-Kdo乙硫苷供体,总收率24%,立体选择性单一,其结构经~1H NMR和~(13)C NMR确证。     

1-Fluoropyridinium triflates: versatile reagents for transformation of thioglycoside into O-glycoside, glycosyl azide and sulfoxide

1-Fluoropyridinium triflates are versatile reagents to transform thioglycoside into O-glycoside, glycosyl azide and sulfoxide. The electronic nature of the substituents on the pyridine ring can control their ability to activate thioglycosides.     

Stereoselective Thioconjugation by Photoinduced Thiol-ene Coupling Reactions of Hexo- and Pentopyranosyl d- and l-Glycals at Low-Temperature—Reactivity and Stereoselectivity Study

A comprehensive optimization and mechanistic study on the photoinduced hydrothiolation of different d - and l - hexo- and pentoglycals with various thiols was performed, at the temperature range of RT to −120 °C. Addition of thiols onto 2-substituted hexoglycals proceeded with complete 1,2-cis-α-stereoselectivity in all cases. Hydrothiolation of 2-substituted pentoglycals resulted in mixtures of 1,2-cis-α- and -β-thioglycosides of varying ratio depending on the configuration of the reactants. Hydrothiolation of unsubstituted glycals at −80 °C proceeded with excellent yields and, except for galactal, provided the axially C2-S-linked isomers with high selectivity. Cooling was always beneficial to the efficacy, increased the yields and in most cases significantly raised the stereoselectivity. The suggested mechanism explains the different conformational preferences of the intermediate carbon-centered radicals, which is a crucial factor in the stereoselectivity of the reactions.     

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.     

The α‐Glycosidation of Partially Unprotected N‐Acetyl and N‐Glycolyl Sialyl Donors in the Absence of a Nitrile Solvent Effect

The synthesis of α‐sialosides is one of the most difficult reactions in carbohydrate chemistry and is considered to be both a thermodynamically and kinetically disfavored process. The use of acetonitrile as a solvent is an effective solution for the α‐selective glycosidation of N‐acetyl sialic acids. In this report, we report on the α‐glycosidation of partially unprotected N‐acetyl and N‐glycolyl donors in the absence of a nitrile solvent effect. The 9‐O‐benzyl‐N‐acetylthiosialoside underwent glycosidation in CH₂Cl₂ with a good α‐selectivity. On the other hand, the 4,7,8‐O‐triacetyl‐9‐O‐benzyl‐N‐acetylthiosialoside was converted to β‐sialoside as a major product under the same reaction conditions. The results indicate that the O‐acetyl protection of the sialyl donor was a major factor in reducing the α‐selectivity of sialylation. After tuning of the protecting groups of the hydroxy groups at the 4,7,8 position on the sialyl donor, we found that the 9‐O‐benzyl‐4‐O‐chloroacetyl‐N‐acetylthiosialoside underwent sialylation with excellent α‐selectivity in CH₂Cl₂. To demonstrate the utility of the method, straightforward synthesis of α(2,9) disialosides containing N‐acetyl and/or N‐glycolyl groups was achieved by using the two N‐acetyl and N‐glycolyl sialyl donors.     

Cesium Carbonate–Promoted Michael‐Type Addition of Thiols to Hex‐1‐en‐3‐ulose: A Practical Synthesis of 2‐Deoxy‐1‐thio‐α‐hexopyranosid‐3‐ulose Template

The template 2‐deoxy‐1‐thio‐α‐hexopyranosid‐3‐ulose was synthesized in quantitative yield and high diastereoselectivity by 1,4‐addition of aryl and alkyl thiols to hex‐1‐en‐3‐ulose promoted by cesium carbonate in THF.     

Photoinitiated Thiol-ene Reactions of Enoses: A Powerful Tool for Stereoselective Synthesis of Glycomimetics with Challenging Glycosidic Linkages

Thioglycosides and C-glycosides represent pharmacologically useful classes of glycomimetics that possess a high degree of biological stability. One emerging tool for the stereoselective synthesis of thioglycosides is the photoinitiated addition of thiols to unsaturated sugars. Moreover, thiyl radical-mediated reactions of exo-glycals and 1-substituted endo-glycals offer facile routes to β-C-glycosidic structures. This Concept article summarizes the thiol-ene coupling strategies developed recently by our group and Somsák's group for the synthesis of several kinds of glycomimetics which are difficult to synthesize by conventional methods. One unusual characteristic of the thiol-ene reactions of endo-glycals is that heating inhibits, whereas cooling promotes the reaction. This unique temperature dependence as well as the effects of the enose structures and thiol configurations on the efficacy and stereoselectivity of the reactions are also discussed.     

Synthesis of saccharide precursors for preparation of potential inhibitors of glycosyltranferases

Ethyl 6-O-tert-butyldimethylsilyl-3,4-di-O-acetyl-2-thio-α-D-fructofuranoside (Va), its β-analog (Vb); as well as benzyl 6-O-tert-butyldimethylsilyl-3,4-di-O-acetyl-2-thio-α-D-fructofuranoside (Xa) and its β-analog (Xb), having an unprotected OH group at C-1, were prepared by sequential synthesis starting from commercially available D-fructose. These compounds represent suitable nucleophiles for the preparation of model carbohydrate mimetics of a glycosyltransferase inhibitor type in transition state. The structures of all compounds were confirmed by NMR spectral data and elemental analyses.     

Per-O-Benzylated Ethyl 5-N-Acetyl-α-thiosialoside as a Glycosyl Donor for α-Silylation

Abstract

Per-O-benzylated ethyl 5-N-acetyl-α-thiosialoside 1 was synthesized and its reactivity as a sialyl donor was investigated. It was demonstrated that the reactions of 1 with various primary and secondary alcohol acceptors, including monosaccharides, gave good to excellent yields (53-92%) and acceptable to excellent α-selectivity (α:β?=?2?～?10:1) , showing its promise for application to sialoglycan synthesis.