Synthesis of a Conformationally Constrained Heparin‐like Pentasaccharide

An octasulfated pentasaccharide 1 having an L‐iduronic acid moiety in a fixed 1C4 conformation was synthesized by the coupling of a triosyl donor 3 with a disaccharide acceptor 4 followed by deprotection and O‐sulfation. The acceptor 4 was prepared from the fully acetylated 5‐C‐allyl‐β‐D‐glucose building block 7 by means of a TMSOTf‐promoted glycosylation, intramolecular substitution and ozonolysis of the olefinic bond as the key reactions. Compound 1 showed very low activity in an antithrombin 111‐mediated anti‐Xa assay; this reflects the importance of the presence of a flexible L‐iduronic acid moiety in heparin‐like antithrombotics.