Six-Step Total Synthesis of Azaspirene

Abstract

The total synthesis of (+/-)-azaspirene (1) was achieved in a total of six steps from commercially available materials. Keys to the conciseness of our synthetic approach were the effective gamma-lactam formation from linear precursor 36 and successful tandem epoxidations of gamma-lactam 34 to afford alpha,beta-epoxy-gamma-hydroxy-gamma-lactam intermediate 14. While our streamlined synthesis of azaspirene (1) sought inspiration from its biogenetic hypothesis, experimentally observed chemical reactivity of biosynthetically relevant precursors conversely provides insights to the biological origin of this natural product.