Total Synthesis of Bryostatin 16 using a Pd-Catalyzed Diyne-Coupling as Macrocyclization Method and Synthesis of C20-epi-Bryostatin 7 as a Potent Anticancer Agent

摘要

Asymmetric total synthesis of bryostatin 16 was achieved in 26 steps in the longest linear sequence/39 total steps from aldehyde >10. A Pd-catalyzed alkyne-alkyne coupling was employed for the first-time as a macrocyclization method in a natural product synthesis. A route to convert bryostatin 16 to a new family of bryostatin analogues was developed. Toward the end, 20-epi-bryostatin 7, was synthesized from a bryostatin 16-like intermediate; and the key step involves a Re-catalyzed epoxidation/ring-opening reaction. Preliminary biological studies indicated that this new analogue exhibits nanomolar anti-cancer activity against several cancer cell lines.