Total synthesis of tricyclic marine alkaloids

The purpose of this review is to describe some of our achievements in the total synthesis of the tricyclic marine alkaloids isolated from the ascidians such as fasicularin, lepadiformine, and cylindricine C. The first total synthesis of (+/-)-fasicularin and (+/-)-lepadiformine was accomplished employing a stereocontrolled intramolecular hetero-Diels-Alder reaction of an N-acylnitroso moiety to an exocyclic diene. The synthesis of natural (-)-enantiomer of lepadiformine was then undertaken using a highly efficient protocol involving a new variant of an N-acyliminium ion-initiated intramolecular spirocyclization. These syntheses of lepadiformine led to revision of the published structure of the natural product, formerly assigned incorrectly, and established its absolute stereochemistry to be 2R,5S,10S,13S. The developed strategy based on the spirocyclization was also applied to the total synthesis of (+)-cylindricine C and (-)-fasicularin. The ability of fasicularin to damage DNA by acting as an alkylating agent was investigated.