Phenyl ester prodrugs, hydrolysis

C. Altomare, A. Carotti, S. Cellamare, M. Ferappi, R. Cagiano, G. Renna, QSAR Analysis of Chemical and Serum-Catalyzed Hydrolysis of Phenyl Ester Prodrugs of Nipecotic Acid , Int. J. Pharm. 1988, 48, 91 -102. 

One must be careful not to generalize from the above discussion that hydrolysis of pivaloyl esters will always be slow. Indeed, a notable exception may well exist for monoesters of catechols, where intramolecular catalysis accelerates hydrolysis. This was seen for L-3-[3-hydroxy-4-(pivaloyl-oxy)phenyl] alanine (8.81 4-pivaloyl-L-dopa), a potentially valuable prodrug of L-dopa [114], When given to rats and dogs, 4-pivaloyl-L-dopa displayed markedly longer duration of action and a higher bioavailability of L-dopa than the drug itself complete conversion to L-dopa was noted in rat. The... 

---