Synthesis of biologically relevant steroidal spiro β-lactams from dienamides through the cascade 4-endo N-cyclization/aerobic oxidation sequence

Abstract

The steroid nucleus and β-lactam are prevalent in natural products and drug molecules, the compounds containing such fragments always possess diverse and interesting biological profiles. Presented here is an unprecedented cascade 4-endo N-cyclization/aerobic oxidation sequence that enables the synthesis of biologically relevant steroidal spiro β-lactams from dienamides. Of note, two continuous quaternary chiral centers were constructed simultaneously in this process, and the title compounds bearing the OH and CN groups are highly functionalized, allowing for late-stage transformations for construction of diverse compound library. The protocol has several advantages such as mild reaction conditions and short reaction time, therefore could serve as a new strategy for synthesizing β-lactams.

Keywords: Cascade reactions; Dienamides; Steroids; β-Lactams.