| Popis: |
Hydrolysis of the cis-methyl ester of 3′-deoxy-3′-thiothymidine 3′-S,5′-O-cyclic(phosphorothiolate) (1a) has been followed by HPLC and MS. At pH 5 first order in hydroxide ion. The uncatalyzed and acid-catalyzed reactions yield two thiophosphate diesters, the 3′-S,5′-O-cyclic phosphorothiolate 2 and 3′-S-phosphorothiolate methyl ester 3, in a 9:1 and 1:3 molar ratio, respectively. The hydroxide ion catalyzed reaction gives the endocyclic P−O and P−S bond-cleavage products (3 and 4, respectively) in a 1:2 molar ratio. The pH-independent reaction is suggested to take place by attack of a water molecule on the carbon atom and concomitant C−O bond rupture, whereas the alkaline and acidic reactions involve attack of the nucleophile on the phosphorus atom and formation of a pseudorotating thiophosphorane intermediate. Under acidic conditions, cleavage of the N-glycosidic linkage competes with the phosphoester hydrolysis, corresponding to 20% of the hydrolysis products at pH < 1. |
