A catalytic enantioselective route to hydroxy-substituted quaternary carbon centers: Resolution of tertiary aldols with a catalytic antibody

Aldolase antibody 38C2-catalyzed resolutions of tertiary aldols were studie d. Tertiary aldols proved to be very good substrates for antibody catalyzed retro-aldol reactions. The catalytic proficiency, (k(cat)/K-M)/k(uncat), o f the antibody for these reactions was on the order of 10(10) M-1. A fluoro genic tertiary aldol allowed for the quantitative study of enantiomeric exc ess as a function of reaction conversion, revealing an E value of ca. 160 i n this case. Study of a variety of substrates demonstrated that antibody-ca talyzed retro-aldolization provides rapid entry to highly enantiomerically enriched tertiary aldols, typically >95% ee, containing structurally varied , heteroatom-substituted quaternary carbon centers. The utility of this app roach to natural product syntheses has been demonstrated with the syntheses of (+)-frontalin, the side chain of Saframycin H, and formal syntheses of (+)- and (-)-mevalonolactone.