Catalytic antibody route to the naturally occurring epothilones: total synthesis of epothilones A-F.
Naturally occurring epothilones have been synthesized starting from enantiomerically pure aldol compounds 9-11, which were obtained by antibody catalysis. Aldolase antibody 38C2 catalyzed the resolution of (+/-)-9 by enantioselective retro-aldol reaction to afford 9 in 90% ee at 50 % conversion. Compounds 10 and 11 were obtained in more than 99% ee at 50% conversion by resolution of their racemic mixtures using newly developed aldolase antibodies 84G3, 85H6 or 93F3. Compounds 9, 10 and 11 were resolved in multigram quantities and then converted to the epothilones by metathesis processes, which were catalyzed by Grubbs' catalysts.
Sinha
S C
SC
Department of Molecular Biology and the Skaggs Institute for Chemical Biology, the Scripps Research Institute, La Jolla, California 92037, USA. subhash@scripps.edu
Sun
J
J
Miller
G P
GP
Wartmann
M
M
Lerner
R A
RA
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis; D017151:Antibodies, Catalytic / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D034261:Epothilones; D004852:Epoxy Compounds / Q000138:chemical synthesis*; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D006241:Haptens / Q000378:metabolism; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009231:Myxococcales / Q000378:metabolism; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis*
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D017151:Antibodies, Catalytic; D000970:Antineoplastic Agents; D034261:Epothilones; D004852:Epoxy Compounds; D006241:Haptens; D018942:Macrolides; D013844:Thiazoles; C121425:epothilone E; C426625:epothilone F; C426624:epothilone C; C093787:epothilone A; D005634:Fructose-Bisphosphate Aldolase; C114026:desoxyepothilone B; C093788:epothilone B