Synthetic Approaches to Novel Thiosugar Scaffolds Containing α,β‐Unsaturated Carbonyl Groups

Abstract

The synthesis of new classes of highly functionalized thiosugar derivatives containing α,β‐unsaturated carbonyl functions has been accomplished through simple and efficient strategies. 5‐Thiosugar‐fused butenolides and a 5‐thiohex‐1‐enopyran‐3‐ulose were constructed from easily available starting 3‐uloses by practical and reliable approaches. The reaction sequence used for the bicyclic fused derivatives involved Wittig olefination of protected pento‐ or hexofuran‐3‐uloses, introduction of a sulfhydryl group at C‐5 of the intermediate unsaturated ester and acid‐promoted deprotection, which allowed intramolecular lactonization and conversion into the 5‐thiopyranose form. For the synthesis of a 5‐thiohex‐1‐enopyran‐3‐ulose, a sulfhydryl functionality was introduced at C‐5 on a masked 3‐ulose derived from 1,2:5,6‐di‐O‐isopropylidene‐α‐D‐ribo‐hexofuranos‐3‐ulose. Acidhydrolysis displaced the equilibrium towards the 5‐thiopentopyran‐3‐ulose, which on pyridine‐mediated acetylation underwent 1,2‐elimination of acetic acid to give the desired α,β‐unsaturated 5‐thiopyranulose. This straightforward pathway provided the target compound in 37 % overall yield. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)