Fredericamycin A is a highly functionalized hexacyclic molecule whose unusual structure was reported in 1982. In vitro and in vivo biological studies have established its exceptionally high activity in a wide variety of anticancer screens and, as a consequence, Fredericamycin A is being very seriously considered for clinical evaluation for the treatment of human cancers. Because of its novel structure Fredericamycin is also a valuable structural lead for new chemotherapeutic agents. Nothing is known, however, about Fredericamycin A's mechanism of action. We have very recently completed the first synthesis of Fredericamycin A. The objective of the proposed work is to apply the chemical knowledge acquired during the course of the synthesis to prepare by total synthesis a variety of structural analogs designed to determine Fredericamycin A's mechanism of action, which should allow the preparation of analogs which are therapeutically superior to Fredericamycin.
