Highly Efficient and Scalable Synthesis of Clionamine D

Herein we describe an efficient and scalable synthesis of clionamine D (4), a special member with autophagy bioactivity and an unprecedented spirobislactone side chain in the novel aminosteroid clionamines. This synthesis features a quick access to alpha-methylene-gamma-lactone 8 and a Mn(OAc)(3)-mediated radical [3 + 2] reaction to assemble the unique spirobislactone unit. Clionamine D (4) can also serve as a key synthetic precursor to other clionamine members.