Synthetic studies toward the total synthesis of amphidinolide B1
As one of the most potent cytotoxic compounds of amphidinolide family, amphidinolide B1 was isolated from a culture of amphidinium genus free-swimming dinoflagellate.l In addition to its intriguing bioactivity, amphidinolide B1 has some attractive structural features including a C13-C15 highly substituted diene, an unusual allyl epoxide moiety, nine stereocenters and 26-membered macrolactone skeleton. Although numerous synthetic efforts toward the total synthesis of amphidinolide B1 have been published, it remains an unconquered target. In our synthetic study, many useful protocols have been developed. To establish the C13-C15 diene, we applied a novel Fleming-type coupling and subsequent dehydration sequence. A highly diastereoselective chelation controlled aldol between aldehyde 104 and ketone 105 was affected to form C18 stereocenter as a single isomer. The macrocycle skeleton was established via a spontaneous intramolecular Wadsworth-Emmons olefination in an excellent yield and stereoselectivity. A novel sequence of selenide incorporation and oxidative elimination of selenide 416 provided the unusual allyl epoxide 417 as a single isomer. The only challenge remains in this total synthesis is two deprotection steps.