Studies on models for tetrahydrofolic acid. 8. Hydrolysis and methoxyaminolysis of amidines

The hydrolyses and methoxyaminolyses of a series of cyclic amidines and an acyclic analogue were examined in order to assess the possible importance of stereoelectronic control on the breakdown of the ensuing tetrahedral intermediates and to identify kinetically significant steps between these intermediates and the respective kinetic or thermodynamic isomers. All cyclic amidines react to form initially the product of kinetic control despite apparent conformational restrictions followed by decay to the thermodynamic isomers. The latter process unlike formation of the kinetic isomer is subject to general catalysis. Net formyl transfer to the attacking methoxyamine was also demonstrated in employing a cyclic amidine. The implication of these findings to the enzyme-catalyzed transfer of a one carbon unit from 5,10-methenyltetrahydrofolate to glycinamide ribonucleotide is discussed.