Antibody catalysis of a disfavored chemical transformation.
Organic reactions are often limited by stereoelectronic constrains that appear along the reaction coordinate. An antibody has been generated that overcomes these constraints and catalyzes a highly disfavored chemical transformation. The antibody facilitates the difficult 6-endo-tet ring closure of an epoxy-alcohol to form a tetrahydropyran. The catalyzed process is in formal violation of what has become known as Baldwin's rules for ring-closure reactions. In addition to controlling the regiochemistry of the disfavored cyclization reaction, these catalytic antibodies resolve enantiomeric substrates to afford a stereochemically pure product. The principles demonstrated in this study may be applicable to other disfavored chemical processes.
Janda
K D
KD
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
Shevlin
C G
CG
Lerner
R A
RA
D000906:Antibodies / Q000378:metabolism*; D002384:Catalysis; D004798:Enzymes / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007202:Indicators and Reagents; D007536:Isomerism; D007700:Kinetics
D000906:Antibodies; D004798:Enzymes; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents