The practical synthesis of a novel and highly potent analogue of bryostatin.
Macrocycle 1 is a new highly potent analogue of bryostatin 1, a promising anti-cancer agent currently in human clinical trials. In vitro, 1 displays picomolar affinity for PKC and exhibits over 100-fold greater potency than bryostatin 1 when tested against various human cancer cell lines. Macrocycle 1 can be generated in clinically required amounts by chemical synthesis in only 19 steps (LLS) and represents a new clinical lead for the treatment of cancer.
Wender
Paul A
PA
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. wenderp@stanford.edu
Baryza
Jeremy L
JL
Bennett
Chad E
CE
Bi
F Christopher
FC
Brenner
Stacey E
SE
Clarke
Michael O
MO
Horan
Joshua C
JC
Kan
Cindy
C
Lacôte
Emmanuel
E
Lippa
Blaise
B
Nell
Peter G
PG
Turner
Tim M
TM
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D054713:Bryostatins; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D018942:Macrolides; D011493:Protein Kinase C / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1; D011493:Protein Kinase C