Total Synthesis of Antimicrobial (+)-Streptoaminal-9n via Staudinger-aza-Wittig Reaction

A novel lipidic metabolite, spirohemiaminal, exhibited substantial growth inhibition of several bacteria, including Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. We report herein the successful total synthesis of (+)-streptoaminal-9n, in 13 steps starting from a chiral epoxide synthesized from l-(-)-malic acid. Our synthetic approach to (+)-streptoaminal-9n is based on the utilization of an intramolecular Staudinger-aza-Wittig cyclization reaction for the construction of a cyclic imine core bearing two stereocenters essential for spirohemiaminal formation. Other key reactions include intramolecular oxa-Michael addition, E-selective Wittig olefination, and regioselective opening of an epoxide with an organocuprate.