MODELS OF FOLATE COFACTORS 17. METHYLATION OF 1,3-DIMETHYL-6-METHYLAMINO-URACIL BY A 5,10-CH2-H4FOLATE MODEL. THE FIRST MIMIC OF THE OVERALL dTMP SYNTHASE REACTION

Article abstract of DOI:10.1016/S0040-4020(01)81684-7

2-Tosyl-1,2,3,12b-tetrahydroimidazo<1,5-f>phenanthridine (6) was prepared in five steps from 6-chloromethylphenanthridine (1) in an overall yield of 50percent.The reaction of 6 with 1,3-dimethyl-6-methylaminouracil (8) in CH₃CN/TFA (100:1) at 50-80 deg C, gave a mixture of products from which 1,3-dimethyl-6-methylaminothymine (9a) could be isolated.This constitutes a mimic of the overall dTMP synthase reaction in transferring both a methylene unit and a hydride equivalent from the cofactor model 6 to the 5-position of a uracil derivative.The other products which are formed in the reaction of 6 with 8 are derived from the reaction of the exocyclic intermediate C, formed in the carbon transfer step, with nucleophiles present in the reaction mixture.