Specific inhibitors in vitamin biosynthesis. Part 8. Syntheses of some functionalised 7,7-dialkyl-7,8-dihydropterins

Abstract

The synthesis of a variety of functionalised blocked 7,8-dihydropteridines is described. The functional groups were chosen to provide compounds with potential for investigating the protein chemistry of enzymes in the pathway leading to dihydrofolate and, in particular, of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase. The potential of 7-substituents to provide sites of attachment of inhibitors to columns for affinity chromatography was explored but the extent of the study was curtailed by the restricted applicability of nitrosyl chloride addition to alkenes, a reaction used in the synthesis of pteridine precursors. The syntheses of two compounds, a 6-trichlorophenoxymethyldihydropteridine and of a thiadiazolopteridine, designed to have enhanced transport properties, are also described.