119880-74-9Relevant academic research and scientific papers
Prodrugs of Phosphonoformate: Products, Kinetics and Mechanisms of Hydrolysis of Dibenzyl (Methoxycarbonyl)phosphonate
Mitchell, Antony G.,Nicholls, Dave,Walker, Ian,Irwin, William J.,Freeman, Sally
, p. 1297 - 1304 (2007/10/02)
Dibenzyl (methoxycarbonyl)phosphonate (1) has been prepared by the reaction of benzyl alcohol with (methoxycarbonyl)phosphonic dichloride.The hydrolysis of 1 proceeded rapidly, with a half-life of 60 min at 36.4 deg C and pH 7.4, by two main pathways.The dominant pathway (k1, 6.56 * 10-3 min-1) yielded the diester, benzyl (methoxycarbonyl)phosphonate (2) and benzyl alcohol (3), with P-O cleavage.The second (k2, 3.55 * 10-3 min-1) gave dibenzyl phosphite (4), possibly arising from the hydrolysis of the carboxyl ester followed by decarboxylation.Benzyl phosphite (5) was also observed, which arises from the hydrolysis of 4 with P-O cleavage (k5, 9.04 * 10-4 min-1).Other products formed in small amounts were, benzyl (benzyloxycarbonyl)phosphonate (6) (k3, 3.59 * 10-4 min-1) and dibenzyl phosphate (7) (k4, 4.24 * 10-4 min-1).The rapid and complicated hydrolysis of 1, involving four competitive reactions, two of which involve C-P bond cleavage, suggests that triesters of phosphonoformate are unlikely to be suitable prodrug forms.
