Total synthesis of optically active mitomycin C 1, FR-900482 2, saframycin A 3, renieramycin A 4, and prianosin A 5 are proposed. In addition, synthesis of a variety of mitomycin analogs is proposed. Optically active mitomycins will be synthesized based on our highly efficient synthetic pathway developed for racemic mitomycins. The same pathway allows synthesis of a variety of mitomycin analogs which cannot be derived from natural mitomycins. FR-900482, a recently isolated antitumor antibiotic, is equal to or even more active than mitomycin C. Results of our preliminary studies on this fascinating molecule are highly promising and have opened the way for the synthesis of a variety of mitomycin-like double alkylating agents of DNA, including epoxymitomycin and its prodrugs. Total syntheses of saframycin A, an interesting antitumor agent, and renieramycin A are approaching the final stages. We will be able to prepare sufficient amount of renieramycin A, a scarcely available natural product isolated from a marine sponge, for antitumor screening. Prianosin A belongs to a prianosin-discorhabdin family of unique cytotoxic natural products isolated from marine sponges. The proposed straightforward synthetic pathway could be used for synthesizing a variety of analogs which may exhibit improved pharmacological activities.
