Thiocarbonyl Ylide Chemistry Enables a Concise Synthesis of (±)-Hippolachnin A

Hippolachnin A (1) is
an antifungal polyketide that
bristles with ethyl groups mounted onto a caged heterotricyclic core.
It has shown potent activity against Cryptococcus neoformans, a yeast that can affect immunocompromised patients as an opportunistic
pathogen. Herein we describe a concise, diversifiable, and scalable
synthesis of (±)-hippolachnin A (1). It features
a powerful photochemical opening step, a diastereoselective addition
of an ethyl cuprate and an unusual strategy to install two additional
ethyl groups that makes use of a thiocarbonyl ylide generated in situ.