Models of folate coenzymes—VII : Synthesis and carbon transfer reactions of N 5,N 10-methenyl and N 5,N 10-methylenetetrahydrofolate models

Abstract

Carboxylate esters react with 1,2-diaminoethanes to yield imidazolines, which upon consecutive reaction with acetic anhydride or tosyl chloride and methyl iodide give imidazolinium salts that serve as models of N 5,N 10-(CH +)-tetrahydrofolate (THF) coenzymes ( 7a, b and 18a, b). Reduction of the latter salts with sodium borohydride or reaction with anions (R −) give the corresponding 5,10-[CH(H,R)]-THF models. Mono- and bifunctional nucleophiles react with 18a, b to yield carbon-transfer products 6-Alkylamino-1,3-dimethyluracils react with 1 tosyl-3,4,4-trimethylimidazolidine (the reduction product of 18b), in the presence of acetic acid, to form carbon transfer products via a mechanism which bears close analogy to the mechanism of action of thymidylate synthetase.