INSTALLATION OF THE PYRUVATE UNIT IN GLYCIDIC ALDEHYDES VIA A WITTIG OLEFINATION MICHAEL ADDITION SEQUENCE UTILIZING A THIAZOLE-ARMED CARBONYL YLID - A NEW STEREOSELECTIVE ROUTE TO 3-DEOXY-2-ULOSONIC ACIDS AND THE TOTAL SYNTHESIS OF DAH, KDN, AND 4-EPI-KDN

A method for the installation of the (2-thiazolylcarbonyl)methylene group, i.e. a masked pyruvate unit owing to the thiazole to formyl equivalence, in sugar-derived aldehydes has been developed. The strategy involves stereoselective carbon-carbon and carbon-oxygen bond formation, the former consisting of a Wittig olefination with a thiazole-armed carbonyl ylid, the latter involving a conjugate addition of the benzyl oxide anion to the resultant E alpha,beta-enone. This addition was mainly anti (ds 78-85%) to a resident gamma-benzyloxy group in the enone, but changed to syn (ds 70-95%) with a chiral 1,3-dioxolane or 1,3-dioxane ring. The removal of the hydroxy-protecting groups and the consequent cyclization via intramolecular ketalization gave 2-thiazolyl-substituted pyranoses at C-1. The unmasking of the formyl group from the thiazole ring in these compounds afforded 3-deoxy-2-aldopyranosuloses, which were quantitatively oxidized to pyranosulonic acids. Applications of this strategy to the total synthesis of DAH (D-arabino-heptulosonic), KDN (D-glycero-D-galacto-nonulosonic), and its D-glycero-D-talo epimer, 4-epi-KDN, are described.