A stereoselective approach in preparation of γ-lactam precursors for oxazolomycin’s synthesis

Abstract

A stereoselective approach to C-3′ methyl attached γ-lactam derivatives as the precursors of pyroglutamate core of oxazolomycins is described. The synthesis started from d-xylose and utilized [3,3]-heterosigmatropic rearrangement. The key lactamization was achieved with intramolecular aldol reaction and ring-closing metathesis. The accomplished stereoselective aldol cyclization was elucidated with Zimmerman-Traxler transition state models. Stereoselectivity of the aldol reaction was explained as a consequence of chelation and bridgehead atoms linkage. The present work also encompasses proposed structures of (E)- and (Z)- generated enolates during intramolecular aldol reaction. Although stereocenters were not formed during ring-closing metathesis, a stereospecific reduction of prepared double bond functionality was successfully accomplished.