Regioselectivity and enantioselectivity in an antibody catalyzed hetero Diels-Alder reaction.
The Diels-Alder cycloadditions of trans- and cis-piperylene (1 and 2) to 4-nitroso-N-propylbenzamide (3) were selected as target reactions for the development of catalytic antibodies with regioselective and enantioselective properties (Meekel, A. A. P. Ph.D. Thesis, University of Amsterdam, 1995). The bicyclic systems 10a-c were designed as transition state analogues and employed for the immunization of mice and the generation of monoclonal antibodies. Three of the antibodies, each obtained from immunization with a different hapten, were selected for further characterization of their catalytic activities. Among these, antibody 309-1G7, raised against the protein conjugate of 10c, showed the best rate enhancement (kcat/ kuncat = 2618) in the reaction of cis-piperylene (2) with nitroso dienophile 3. Data obtained from regioselectivity and enantioselectivity analyses demonstrated that antibody 309-1G7 favors the formation of the targeted regioisomer (> 95%), with an ee of 82%.
Meekel
A A
AA
Laboratory of Organic Chemistry, University of Amsterdam, The Netherlands.
Resmini
M
M
Pandit
U K
UK
D000466:Alkadienes / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001549:Benzamides / Q000737:chemistry; D002625:Chemistry, Organic; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008807:Mice, Inbred BALB C; D009603:Nitroso Compounds / Q000737:chemistry; D055601:Organic Chemistry Phenomena; D010420:Pentanes; D013237:Stereoisomerism
C103395:4-nitroso-N-propylbenzamide; D000466:Alkadienes; D000911:Antibodies, Monoclonal; D001549:Benzamides; D009603:Nitroso Compounds; D010420:Pentanes; C011970:1,3-pentadiene