Synthesis of a hapten to be used in development of immunoassays for trans-3'-hydroxycotinine, a major metabolite of cotinine.
4-Carboxyl-substituted analogues of trans-3'-hydroxycotinine were synthesized to be covalently linked to macromolecules for antibody production. 3-Pyridyl-N-methylnitrone was condensed with dimethyl fumarate to give two isomeric isoxazolidines. Hydrogenolysis of the major product [2RS-(2 alpha,3 alpha,3 beta)]-3-carbomethoxy-3- [[(benzyloxy)carbonyl]oxy]-1-methyl-5-oxo-2-(3-pyridinyl)pyrrolidine with Pd/C followed by hydrolysis gave [2RS-(2 alpha,3 beta,4 beta)]-4-hydroxy-1-methyl-5-oxo-2-(3-pyridinyl)-3- pyrrolidinecarboxylic acid. The same compound was also prepared in two steps in high yield starting with dibenzyl fumarate and 3-pyridyl-N-methylnitrone.
Desai
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Division of Chemical Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595.
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D003367:Cotinine / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000378:metabolism*; D006241:Haptens / Q000737:chemistry*; D007118:Immunoassay; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation
D006241:Haptens; C001381:hydroxycotinine; D003367:Cotinine