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.
Asymmetric total synthesis of bryostatin 16 was achieved in 26 steps in the longest linear sequence and in 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 this end, 20-epi-bryostatin 7 was synthesized from a bryostatin 16-like intermediate; 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.
Department of Chemistry, Stanford University, Stanford, California 94305-5080, United States. bmtrost@stanford.edu
Barry M
BM
Trost
Guangbin
G
Dong
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054713:Bryostatins / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*
D000970:Antineoplastic Agents; D054713:Bryostatins; C102705:bryostatin 16; C475531:bryostatin 7; D010165:Palladium