Nature Publishing Group, publisher of Nature, and other science journals and reference works
Nature
my account e-alerts subscribe register
   
Friday 23 June 2017
Journal Home
Current Issue
AOP
Archive
Download PDF
References
Export citation
Export references
Send to a friend
More articles like this

Letters to Nature
Nature 374, 143 - 146 (09 March 1994); doi:10.1038/374143a0

Antibody catalysis of a reaction otherwise strongly disfavoured in water

Doron Shabat*, Harel Itzhaky*, Jean-Louis Reymond & Ehud Keinan*

*Department of Chemistry, Technion-lsrael Institute of Technology, Technion City, Haifa 32000, Israel
Department of Molecular Biology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, California 92037, USA

SEVERALexamples have been reported recently1 of antibody catalysis2of reactions that are strongly disfavoured because of the high free energy of the transition state. Here we show that catalytic antibodies can be used to promote a particularly useful kind of reaction from a synthetic point of view: one involving an intermediate that is highly unstable in water. We show that an antibody elicited against the quaternary ammonium ion 4a (Fig. 1) catalyses the protonation of the enol ether 1 to form, with complete enantio-selectivity, an oxocarbonium intermediate. This species is highly reactive in water, and would normally react with a water molecule to give the corresponding ketone 2. But the antibody provides a hydrophobic environment that allows the oxocarbonium ion instead to undergo an intramolecular reaction to form an enantiomerically pure ketal 3. This result shows that catalytic antibodies can exclude solvent molecules entirely from crucial steps on the reaction pathway.

------------------

References

1. Lerner, R. A., Benkovic, S. J. & Schultz, P. G. Science 252, 659−667 (1991). | PubMed | ISI | ChemPort |
2. Schultz, P. G. & Lerner, R. A. Acc. Chem. Res. 26, 391−395 (1993). | Article | ChemPort |
3. Banait, N. S. & Jencks, W. P. J. Am. chem. Soc. 113, 7951−7958 (1991). | Article | ChemPort |
4. Pothier, N., Goldstein, S. & Deslongchamps, P. Helv. chim. Acta 75, 604−620 (1992). | Article | ChemPort |
5. Jenks, W. P. Catalysis in Chemistry and Enzymology 52−60 (Dover, New York, 1987).
6. Schmir, G. L. & Gunningham, B. A. J. Am. chem. Soc. 87, 5692−5700 (1965). | Article | ChemPort |
7. Reymond, J.-L., Janda, K. D. & Lerner, R. A. Angew. Chem. int. Ed. engl. 30, 1711−1713 (1991). | Article |
8. Sinha, S. C., Keinan, E. & Reymond, J.-L. Proc. natn. Acad. Sci. U.S.A. 90, 11910−11913 (1993). | ChemPort |
9. Reymond, J.-L., Jahangiri, G. K., Stoudt, C. & Lerner, R. A. J. Am. chem. Soc. 115, 3909−3917 (1993). | Article | ChemPort |
10. Reymond, J.-L., Reber, J.-L. & Lerner, R. A. Angew. Chem. int. Ed. engl. 33, 475−477 (1994). | Article |
11. Jahangiri, G. K. & Reymond, J.-L. J. Am. chem. Soc. 116, 11264−11274 (1994). | Article | ChemPort |
12. Lewis, C., Paneth, P., O'leary, M. H. & Hilvert, D. J. Am. chem. Soc. 115, 1410−1413 (1993). | Article | ChemPort |
13. Sinha, S. C., Keinan, E. & Reymond, J.-L. J. Am. chem. Soc. 115, 4893−4894 (1993). | Article | ChemPort |
14. Schuster, M., Wang, P., Paulson, J. C. & Wong, C.-H. J. Am. chem. Soc. 116, 1135−1136 (1994). | Article | ChemPort |
15. Evans, D. A., Ennis, M. D. & Mathre, D. J. J. Am. chem. Soc. 104, 1737−1739 (1982). | Article | ChemPort |



© 1994 Nature Publishing Group
Privacy Policy