Allylic Phosphate Hydrolysis: Kinetics and Mechanism of Degradation of 3β,17α-Dihydroxy-6α-methylpregn-4-en-20-one 17-Acetate, 3-Phosphate

Abstract

The kinetics and mechanism of degradation of 3β, 17α-dihydroxy-6α-methylpregn-4-en-20-one 17-acetate, 3-phosphate (I) was studied as a function of pH and temperature. At low pH the least stable moiety is the allylic phosphate ester at C3, while the most reactive function at high pH is the acyl ester at position 17. At pH 7 and 37°, the rate of phosphate ester hydrolysis is approximately 104 times faster than hydrolysis of the 17α-acetoxy function. Between pH 4 and 10 at 37° and between pH 2 and 6 at 4°, the rate of phosphate ester hydrolysis is first order with respect to hydrogenion concentration. The major products of allylic phosphate hydrolysis are an epimeric mixture of C3 alcohols, supplying evidence that the reaction occurs principally by carbon—oxygen bond fission. The activation energy for phosphate ester hydrolysis of I is 21.5 ± 0.9 kcal./mole.