Short synthesis of idraparinux by applying a 2-O-methyl-4,6-O-arylmethylene thioidoside as a 1,2-trans α-selective glycosyl donor

Demeter, Fruzsina and Veres, Fanni and Herczeg, Mihály and Borbás, Anikó (2018) Short synthesis of idraparinux by applying a 2-O-methyl-4,6-O-arylmethylene thioidoside as a 1,2-trans α-selective glycosyl donor. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. pp. 1-14. ISSN 1434-193X (Submitted)

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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.

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