ASYMMETRIC ORGANIC-SYNTHESIS WITH CATALYTIC ANTIBODIES

The science of catalytic antibodies has undergone a rapid maturation p rocess within its first nine years of existence. From initial 'proof o f concept' and demonstration of fundamental, enzyme-like characteristi cs, antibodies have been shown to catalyze a remarkably broad scope of organic transformations, including difficult and unfavorable chemical reactions. Yet, the ultimate testing ground for new concepts in organ ic chemistry has always been the synthesis of natural products. Here w e focus on several issues related to the applicability of antibody cat alysis in organic synthesis. We show that (a) in the hydrophobic envir onment of the antibody active site, short-lived intermediates can be f ormed and reacted in a controlled way, thus allowing antibodies to cat alyze reactions that are normally incompatible with aqueous media, (b) the intrinsic order of reactivity (chemoselectivity) in a series of s tructurally related enol ethers and ketals can be inverted from 1:10 i n the uncatalyzed hydrolysis reaction to 1000:1 under antibody catalys ts, and (c) an efficient total synthesis of alpha-multistriatin, an im portant, biologically active natural product can be achieved via antib ody catalysis.