Soft corals are a particularly rich source of structurally novel sesquiterpenoids with a broad range of biological functions. In 2009, chabranol, possessing an unprecedented terpenoid skeleton, namely a cyclopentane ring fused to a tetrahydrofuran ring at C-3 and C-6, was isolated from the soft corals Nephthea chabroli by Duh at National Sun Yat-Sen University. The extremely meager natural supply, novel structural features, and potent biological activities have defined chabranol as an attractive target for total synthesis.

Herein, Prof. SHE Xuegong, a visiting professor of the Lanzhou Institute of Chemical Physics (LICP), CAS, and co-workers report the first total synthesis of (þ)-chabranol in 6 steps with 36.6% overall yield, the enantiomer of the natural product, and the natural product’s absolute configuration was also designated as (3S,4S,5R,6S), which was further confirmed by X-ray experiment. The bicyclo [2.2.1] core of the natural product was efficiently constructed through intramolecular Prins double cyclization.

This short synthesis appears to open a feasible way to design analogues for a structure-activity relationship study.

The work was published in J. Org. Chem. (J. Org. Chem. 2010, 75, 5392–5394).

Abstract of the paper published in J. Org. Chem.