Enol ethers, antibody catalysis

The molecular mechanism of the enantioselective protonation reaction by antibody 14D9 was revealed by a crystal structure analysis [19[. A catalytic carboxyl group AspH 101 was found at the bottom of the catalytic pocket and found to be necessary for catalysis by mutagenesis to Asn or Ala. The mechanism or protonation involves an overall syn addition of water to the enol ether in a chiral binding pocket ensuring complete enantioselectivity (Figure 3.4). 

The control of chemical selectivity is a classical problem in organic chemistry and an antibody s ability to route reactions via disfavored pathways, as in the asymmetric Diels-Ald reaction, has important practical ramifications. Not surprisingly, extension of this approach to the catalysis of other unselective or energetically demanding reactions has become an important focus of research. Syn eliminations [45], cationic olefin cycliza-tions [46], and enol ether hydrolyses [47] are among the processes that have been investigated. For the purposes of the current discussion, however, the regio- and stereoselective reduction of the diketone 21 [48] illustrates what... 

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