The amphidinolides are a family of complex macrolides exhibiting potent and unique antitumor activity. The B-type amphidinolides represent promising leads in the search for new chemotherapeutic agents. Unfortunately, these compounds, isolated from marine dinoflagellates, are only isolable in minute quantities. Although many groups have pursued their total synthesis, no synthetic route currently exists. A novel strategy proposed here investigates the use of the direct aldol reaction promoted by Trost's new dizinc catalysts. The unique nature of this aldol reaction may make possible the development of a sequential, catalytic, asymmetric aldol reaction. This sequential aldol process would allow for rapid, stereocontrolled assembly of the required C18-C22 triol moiety present in the B-type amphidinolides. Formation of the required 26-member macrolide has represented a formidable challenge for previous investigators. Macrocyclization via ring closing metathesis has emerged as a powerful method to allow access to molecules which otherwise may have remained unattainable. For that reason, it is proposed to form the elusive 26-member macrolide of amphidinolide B1 via ring closing metathesis (RCM).
