Asymmetric Total Synthesis of (−)-Azaspirene, a Novel Angiogenesis Inhibitor

The asymmetric total synthesis of (−)-azaspirene, an angiogenesis inhibitor, has been accomplished, establishing its absolute stereochemistry. The key steps are a MgBr2·OEt2-mediated, diastereoselective Mukaiyama aldol reaction, a NaH-promoted, intramolecular cyclization of an alkynylamide, and the aldol reaction of a ketone containing functionalized γ-lactam moiety without protection of tert-alcohol and amide functionalities.