Highly Stereoselective de Novo Synthesis of l-Hexoses

Abstract

An efficient and general de novo synthetic route to enantiomerically pure l-hexoses has been accomplished starting from the heterocyclic homologating agent 5,6-dihydro-1,4-dithiin-2-yl[(4-methoxybenzyl)oxy]methane and methyl α,β-isopropylidene-l-glycerate. The sugar scaffold was constructed by an acid-catalyzed domino reaction, which enabled selective preparation of either methyl 2,3-dideoxy-α-l-threo-hex-2-enopyranosides or 1,6-anhydro-2,3-dideoxy-β-l-threo-hex-2-enopyranose as key intermediates. The subsequent double bond functionalization by syn or anti dihydroxylation reactions allowed introduction of the remaining stereogenic centers, leading to desired orthogonally protected l-hexopyranosides with a high degree of diastereoselectivity and with very good overall yields. These and previous results (based on the use of the corresponding l-erythro epimers) contribute to make our approach general and place it among the few methods able to synthesize the whole series of the rare l-hexoses