Nonclassical Antimetabolites XIX

Nonclassical Antimetabolites XXVII

“…Acylation of ti-mercapto-9H-purine-9-ylpentanol (V) (1) with phenyl chloroformate in pyridine gave the mixed carbonate (VI) in 98% yield; reaction of VI with amonia water afforded the desired 5'carbamate (IX) (3).…”

“…(I) was one-twelfth as effective as I in inhibiting the enzyme; in contrast, the corresponding nucleoside (11) was less than one-sixtieth as effective as the nucleotide (I) (1). Thus, the phosphate contributed more to the binding of 5'-phosphoribosyI moiety of thioinosinate (I) to succinoadenylate kinosynthetase than did the remainder of the oxygen functions in the moiety, as predicted earlier (2); of the three remaining oxygen functions of I, most of the binding was due to the 2'-hydroxyl group (1).…”

“…(I) was one-twelfth as effective as I in inhibiting the enzyme; in contrast, the corresponding nucleoside (11) was less than one-sixtieth as effective as the nucleotide (I) (1). Thus, the phosphate contributed more to the binding of 5'-phosphoribosyI moiety of thioinosinate (I) to succinoadenylate kinosynthetase than did the remainder of the oxygen functions in the moiety, as predicted earlier (2); of the three remaining oxygen functions of I, most of the binding was due to the 2'-hydroxyl group (1). In another study attempting to simulate phosphate binding, the 5'-carbamate (111) of thioinosine (11) was synthesized and evaluated (3) ; I11 showed no inhibition of succinoadenylate kinosynthetase a t the maximum concentration that could be measured, being less than one-fiftieth as effective as thioinosinate (I).…”