Prof. SHE Xuegong, a part-time professor of the Lanzhou Institute of Chemical Physics, and his co-workers have developed a concise, biomimetic 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.

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, the researchers report the first total synthesis of (þ)-chabranol utilizing a biomimetic and highly stereocontrolled strategy in which the absolute configuration of chabranol was also established.

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

The work has received support from the Ministry of Science and Technology of China and the National Natural Science Foundation of China.

The findings have been published in J. Org. Chem. (J. Org. Chem. Vol. 75, No. 15, 2010).

J. Org. Chem. Paper