Sets of aldolase antibodies with antipodal reactivities. Formal synthesis of epothilone E by large-scale antibody-catalyzed resolution of thiazole aldol.
[formula: see text] Three monoclonal aldolase antibodies, generated against a beta-diketone hapten by reactive immunization, catalyzed rapid and highly enantioselective retro-aldol reactions of ent-8a-k, providing optically pure 8a-k by kinetic resolution. Compounds (+/-)-8a, (+/-)-8g, and (+/-)-8k have been resolved in multigram quantities using 0.003, 0.005, and 0.0004 mol% antibody catalysts, respectively. Resolved compounds 8a-k are useful synthons for the construction of epothilones A-E (2-6) and their analogues. Here, a formal synthesis of epothilone E, 6 has been achieved starting from compound 8g.
Sinha
S C
SC
Department of Molecular Biology, Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, California 92037, USA. subhash@scripps.edu
Sun
J
J
Miller
G
G
Barbas
C F
CF
Lerner
R A
RA
D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D034261:Epothilones; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D005634:Fructose-Bisphosphate Aldolase / Q000276:immunology*; D007114:Immunization; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D034261:Epothilones; D004852:Epoxy Compounds; D013844:Thiazoles; C121425:epothilone E; D005634:Fructose-Bisphosphate Aldolase