An Efficient Modular One-Pot Synthesis of Heparin-Based Anticoagulant Idraparinux

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(26), P. 10309 - 10314

Published: June 3, 2019

Idraparinux is a fully O-sulfated α-methyl glycoside of heparin pentasaccharide motif known to interact with the antithrombin III domain and act as anticoagulant. The current most effective synthesis complicated nonstereoselective, requiring numerous stepwise procedures low yields. We report here an efficient modular one-pot involving use glycosyl phosphate 6-O-tert-butyl diphenyl silyl group d-glucuronic acid-containing disaccharide thioglycoside 6-O-acetyl donor building blocks for α-directing glycosylations l-iduronic acceptor block. uronic acid was incorporated in module used avoid late-stage installation these acidic sugars. demonstrated strategy should be applicable assembly other heparan sulfates regiodefined sulfation pattern functional study.

Language: Английский

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Chemical synthesis of marine saponins

Natural Product Reports, Journal Year: 2018, Volume and Issue: 36(5), P. 769 - 787

Published: Dec. 7, 2018

Covering: 1989-2017 Saponins are characteristic metabolites of starfish and sea cucumbers, occasionally also found in sponges, soft coral, small fish. These steroid or triterpenoid glycosides often show remarkable biological pharmacological activities, such as antifungal, antifouling, shark repellent, antitumor anti-inflammatory activities. Over one thousand marine saponins have been characterized; the majority them can be categorized into three major structural types, i.e., asterosaponins, polyhydroxysteroid glycosides, holostane glycosides. Thus far, only 12 synthesized; those representing types were successfully synthesized recently. The syntheses involve preparation aglycones from terrestrial triterpene materials, installation carbohydrate units, manipulation protecting groups. Herein, we provide a comprehensive review on these syntheses.

Language: Английский

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Dissecting the Essential Role of Anomeric β-Triflates in Glycosylation Reactions

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(28), P. 12501 - 12514

Published: June 24, 2020

Glycosylations promoted by triflate-generating reagents are widespread synthetic methods for the construction of glycosidic scaffolds and glycoconjugates biological chemical interest. These processes thought to proceed with participation a plethora activated high energy intermediates such as α- β-glycosyl triflates, or even increasingly unstable glycosyl oxocarbenium-like species, among which only α-glycosyl triflates have been well characterized under representative reaction conditions. Interestingly, remaining less accessible intermediates, yet be experimentally described, seem particularly relevant in α-selective processes, involving weak acceptors. Herein, we report detailed analysis several paradigmatic illustrative examples reactions, employing combination chemical, NMR, kinetic theoretical approaches, culminating unprecedented detection quantification true triflate within donor mixtures. This achievement was further employed stepping-stone characterization anomerization dynamics, along acceptor substitutions, govern stereochemical outcome reaction. The obtained data conclusively show that, highly dissociative reactions β-close ion pair (β-CIP) formation α-glycoside is necessarily preceded bimolecular α → β interconversion, certain circumstances becomes rate-limiting step. Overall, our results rule out prevalence Curtin–Hammett fast-exchange assumption most glycosylations highlight distinct reactivity properties against neutral anionic

Language: Английский

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Synthesis of carbohydrate building blocksviaregioselective uniform protection/deprotection strategies

Organic & Biomolecular Chemistry, Journal Year: 2019, Volume and Issue: 17(20), P. 4934 - 4950

Published: Jan. 1, 2019

Scope 1: sugar is uniformly protected leaving only one (or two) free hydroxyl group; scope 2: deprotected to liberate group.

Language: Английский

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Glycosylation with 3,5-Dimethyl-4-(2′-phenylethynylphenyl)phenyl (EPP) Glycosides via a Dearomative Activation Mechanism

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(12), P. 4806 - 4810

Published: March 13, 2019

A highly effective and versatile glycosylation method is developed, which uses 3,5-dimethyl-4-(2′-phenylethynylphenyl)phenyl (EPP) glycosides as donors NIS/TMSOTf promoter proceeds via an unprecedented dearomative activation mechanism.

Language: Английский

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