ENANTIOSELECTIVE TOTAL SYNTHESIS OF SOME BREVICOMINS USING ALDOLASE ANTIBODY 38C2

Aldolase antibody 38C2 (Aldrich no. 47,995-0) catalyzes the aldol reac tion between hydroxyacetone and aldehyde 7 to give dihydroxyketone 8 a lpha in an enantiomeric excess (ee) >99%. This reaction has been perfo rmed on a semipreparative scale to give the product in 55% yield (ee=9 8%). Aldol 8 alpha can be converted to hydroxybrevicomins ent-5 and en t-6 by reduction and acid-catalyzed cyclization. Antibody 38C2 also ca talyzes the retro-aldol reaction of racemic syn-8. After 52% conversio n, the enantiomeric product (8 beta) is obtained in >99% ee. By using either antibody-catalyzed aldol or retro-aldol reactions, both aldol e nantiomers can be prepared with a single antibody catalyst. This metho dology has been applied in highly enantioselective total syntheses of ten brevicomins.