Sets of aldolase antibodies with antipodal reactivities, formal synthesis of epothilone E by large-scale antibody-catalyzed resolution of thiazole aldol

Three monoclonal aldolase antibodies, generated against beta-diketone hapte n by reactive immunization, catalyzed rapid and highly enantioselective ret ro-aldol reactions of ent-8a-k, providing optically pure 8a-k by kinetic re solution. Compounds (+/-)-8a, (+/-)-8g, and (+/-) 8k have been resolved in multigram quantities using 0,003, 0.005, and 0.0004 mol % antibody catalyst s, respectively. Resolved compounds 8a-k are useful synthons for the constr uction of epothilones A-E (2-6) and their analogues. Here, a formal synthes is of epothilone E, 6 has been achieved starting from compound 8g.