Antibody-Catalyzed Enantioselective Robinson Annulation
J. Am. Chem. Soc. 1997, 119, 8131-8132 8131 Antibody-Catalyzed Enantioselective Robinson Previously, two antibodies 33F12 and 38C2, capable of Annulation catalyzing a broad range of intermolecular aldol reactions between ketone donors and aldehyde acceptor substrates, were produced using the strategy of reactive immunization7,8 with Guofu Zhong,† Torsten Hoffmann,† Richard A. Lerner,*,† ,‡ ,† the â-diketone hapten 1. A carbonyl group of 1 reacts with Samuel Danishefsky,* and Carlos F. Barbas III* the -amino group of the lysine residue within the active site of the antibody to form a tetrahedral hemiaminal which The Skaggs Institute for Chemical Biology subsequently dehydrates and then tautomerizes to the stable and the Department of Molecular Biology vinylogous amide 2 (eq 1). The Scripps Research Institute 10550 North Torrey Pines Road, La Jolla, California 92037 Laboratory for Bioorganic Chemistry The Sloan-Kettering Institute for Cancer Research 1275 York AVenue, New York, New York 10021 ReceiVed March 25, 1997 We report an antibody that is remarkable in that it catalyzes both steps of an important synthetic transformation, the Rob- inson annulation. The Robinson annulation which accomplishes, We first describe an experiment which probed the feasibility in net terms, the conversion of a f c occupies a key role in 1 of antibody catalysis of the cyclodehydration step while organic synthesis. In most instances, the overall annulation is exploring the possibility of kinetic resolution at this step. For comprised of an alkylation (or Michael addition) step leading these purposes, we prepared the (S)- and (R)-versions of to b followed by a cyclodehydration step to give a cycloalkenone compound 3 by known chemistry.9 As shown in Table 1, both f b c.
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