An antibody-catalyzed bimolecular Diels-Alder reaction
- Lawrence Berkeley Laboratory, CA (USA)
There exist over 1,500 known enzymes which carry out a vast array of chemical reactions with remarkable specificity and reaction rates. It is surprising then that there are no documented examples of enzyme-catalyzed pericyclic cycloaddition reactions, yet there are among the most powerful and commonly used reactions in synthetic organic chemistry. The most important of these is the Diels-Alder reaction of a diene with a dienophile, which provides a straightforward and highly stereospecific route to cyclohexene derivatives. Given the importance of this reaction in organic chemistry and its novel mechanism, it was of interest to ask whether a Diels-Alderase enzymatic catalyst could be evolved from an antibody combining site. Generation of antibodies to a structure that mimics the pericyclic transition state for a Diels-Alder reaction should result in an antibody combining site that lowers the entropy of activation {Delta}S{sup {double dagger}} by binding both the diene and the dienophile in a reactive conformation. The authors approach toward the design of a transition-state analogue involves incorporation of an ethano bridge, which locks the cyclohexene ring of hapten in a conformation that resembles the proposed pericyclic transition state for the Diels-Alder reaction of cisoid diene with dienophile. The authors now report that antibodies generated to the transition-state analogue catalyze the addition of the acyclic water-soluble diene to the maleimide derivative to give the cyclohexene product.
- OSTI ID:
- 5452163
- Journal Information:
- Journal of the American Chemical Society; (United States), Journal Name: Journal of the American Chemical Society; (United States) Vol. 112:20; ISSN 0002-7863; ISSN JACSA
- Country of Publication:
- United States
- Language:
- English
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