Synthesis of (+)-Ophiobolin A

Reformatsky reaction - sesterterpenes - ring-closing metathesis

Significance

(+)-Ophiobolin is a naturally occurring sesterterpene isolated from the pathogenic plant fungus Ophiobolus miyabeanus in 1958. It exhibits bioactivity against a range of nematodes, fungi, and bacteria. Herein, the first total synthesis of (+)-ophiobolin is reported.

Comment

This synthesis utilizes Utimoto’s conditions (Tetrahedron Lett. 1988, 29, 1041) for the Reformatsky-type coupling of α-bromo ketone C and aldehyde B in high yield. Stereoselective hydrogenation and methyl addition are utilized to install the stereocenters at C2 and C3 with excellent selectivity. A ring-closing metathesis is used to form the unsaturated eight-membered ring.