Total synthesis of colombiasin A and determination of its absolute configuration.

The total synthesis of the recently reported marine natural product colombiasin A (1) and determination of its absolute configuration are reported. Two Diels-Alder cycloadditions and a palladium-catalyzed rearrangement are employed as key reactions to construct the tetracyclic framework of the target molecule. The enantioselective synthesis of colombiasin A utilizes Mikami's [(S)-BINOL-TiCl2] catalyst to asymmetrically introduce the first chiral center during the initial Diels-Alder reaction and, in conjunction with X-ray crystallographic analysis of a bromine containing derivative, led to the assignment of the absolute configuration of the natural product.