A Streamlined Asymmetric Synthesis of Substituted Geissman-Waiss Lactones, Oseltamivir precursors and peptidyl hydroxylactams from (–)-Azidocyclohexenol

The asymmetric synthesis of methyl or pentyloxy N,O-bicyclic γ-butyrolactone lactams, 6-aminocyclohex-3-ene-1,2-diol (an oseltamivir precursor) and β-hydroxy lactam tripeptide, starting from (-)-(1S,2S)-1azido-2-hydroxycyclohexene is hereby described.Synthetic transformations in the developed protocols include a linear relay of reduction/protection of the azide, allylic hydroxylation, alcoholysis, oxidative cleavage promoting lactonization/lactamization sequences and methylation.This route provides a simple synthetic pathway towards necine alkaloid derivatives, the antiviral drug oseltamivir (Tamiflu) and peptides incorporating rigid lactam units for foldamer synthesis thus extending the usefulness of our previously reported asymmetric synthetic methodology.