Synthesis of (1S,2S,3R,8S,8aR)-1,2,3,8-tetrahydroxy-6-oxa-5-thioxoindolizidine: A stable reducing swainsonine analog with controlled anomeric configuration

摘要

The title indolizidine, a ring-modified analog of the potent mannosidase inhibitor (-)-swainsonine, has been prepared by intramolecular nucleophilic addition of the sp(2)-type nitrogen atom of a preformed 1,3-oxazine-2-thione heterocycle to the masked aldehyde group in a D-mannose precursor; the stereochemistry of the generated aminoacetalic stereocenter is governed by the generalized anomeric effect, the pseudoanomeric hydroxyl group adopting an axial orientation that mimics that of alpha-D-mannopyranoside aglycons. [References: 27]