Short Synthesis of Idraparinux by Applying a 2‐O‐Methyl‐4, 6‐O‐arylmethylene Thioidoside as a 1, 2‐trans‐α‐Selective Glycosyl Donor. Issue 48 (6th December 2018)

• Record Type: Journal Article
• Authors: Demeter, Fruzsina; Veres, Fanni; Herczeg, Mihály; Borbás, Anikó
• Is Part Of: European journal of organic chemistry. Issue 48(2018)
• Page Start: 6901
• Page End: 6912
• Publication Date: 2018-12-06
• Subjects: Hydroboration -- Oxidation -- Diastereoselectivity -- Glycosylation -- Heparin; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201801349
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : The fully O ‐sulfated, O ‐methylated, heparin‐related anticoagulant pentasaccharide idraparinux was prepared by a new synthetic pathway in 38 steps using d ‐glucose and methyl α‐d ‐glucopyranoside as starting materials, with 23 steps for the longest linear route. The l ‐idose‐containing GH fragment was obtained by a short and straightforward synthesis whereby a 4, 6‐cyclic‐acetal‐protected l ‐idosyl thioglycoside bearing a C2‐nonparticipating group was used as the α‐selective glycosyl donor. The novel l ‐idose donor was prepared with high chemo‐ and stereoselectivity by hydroboration–oxidation‐based C5 epimerization starting from an orthogonally protected α‐thioglucoside. The assembly of the pentasaccharide backbone was achieved by an F +GH and DE +FGH coupling sequence with full stereoselectivity in each glycosylation step. Abstract : Our new route to idraparinux is based on a short and straightforward synthesis of a 4, 6‐cyclic‐acetal‐protected l ‐idosyl thioglycoside bearing a C2‐nonparticipating group, which can be used directly as an α‐selective glycosyl donor building block. The assembly of idraparinux was achieved by an F +GH and DE +FGH coupling sequence with full stereoselectivity in each glycosylation step.