The Viridiofungins are a family of potently fungicidal anti-fungal agents isolated in 1993 by Merck, the absolute structure of which was assigned through total synthesis of the trimethyl ester of Viridiofungin A.  The published syntheses of these compounds are not amenable to medicinal chemistry investigations, and thus we embarked on a programme of research to find a novel, enantioselective synthesis.

Here we describe our successful, concise enantioselective route to derivatives of these medicinally interesting compounds the key steps of which are an asymmetric aldol reaction, a diastereoselective alkylation and a geometrically selective cross metathesis reaction.  Both the length (eight steps from commercially available materials) and yield (3-26% depending on the target) of this synthesis compares extremely favourably with published syntheses (27-18 steps, 2-7% overall yield).  Additionally, there is considerable flexibility in the final three steps with the potential for easy variation of electrophile, amine, and cross-metathesis partner.