Total synthesis of 10-isocyano-4-cadinene and its stereoisomers and evaluations of antifouling activities.

ABSTRACT

The first enantioselective total synthesis of 10-isocyano-4-cadinene, a marine sesquiterpene isolated from nudibranchs of the family Phyllidiidae, and determination of its absolute stereochemistry were achieved. 10-Isocyano-4-cadinene is expected to be a novel nontoxic antifouling agent. In the synthesis, intermolecular Diels-Alder reaction and samarium diiodide induced Barbier-type cyclization were employed as key steps. The absolute configuration of 10-isocyano-4-cadinene was determined as (1S,6S,7R,10S) by comparison of the optical rotations between natural and synthetic samples. In addition, the authors successfully synthesized 10-epi- and di-1,6-epi-10-isocyano-4-cadinene through the same synthetic pathway. Antifouling activities against Balanus amphitrite with the cadinenes were also evaluated.