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Application of the EF and GH Fragments to the Synthesis of Idraparinux

Author:
Łopatkiewicz, Grzegorz, Buda, Szymon, Mlynarski, Jacek
Source:
Journal of organic chemistry 2017 v.82 no.23 pp. 12701-12714
ISSN:
1520-6904
Subject:
cellobiose, chemical reactions, chemical structure, glucose, organic chemistry, organic compounds
Abstract:
A novel total synthesis of fully protected idraparinux has been achieved. A short and efficient protocol for the synthesis of the EF fragment of idraparinux and its C5′-epi analogue (GH unit) has been developed. The same cellobiose unit was transformed in 14 steps into the fully protected EF and GH disaccharide fragments. The key step of this approach is an epimerization of C5 by an elimination–addition sequence leading to l-ido disaccharide (GH unit) with a total yield of 24% (36% for the EF fragment). 1,6-Anhydro ring opening gave suitable substrates for efficient synthesis of fully protected idraparinux. The fully protected antithrombotic pentasaccharide idraparinux was synthesized in 23 steps for the longest linear route, with a 1.7% overall yield from d-cellobiose and d-glucose.
Agid:
5864593