In alkaline media the 2-, 3-, and Cmonohexanoates of lincomycin rapidly isomerize, each entering into facile equilibrium with the other two, accompanied by hydrolysis of each species to lincomycin. The concentration-time curves of the three esters and of lincomycin as observed in a single experiment provide information about the kinetic rate constants. By using a digital computer and a nonlinear estimation program, it is possible to estimate simultaneously the four isomerization rate constants and the three hydrolysis rate constants. Estimates of the seven rate constants agree satisfactorily when either the 2-, 3-, or 4-hexanoate is the starting material, providing evidence that the postulated mechanism is correct. Acyl migration between the cis 3-equatorial and Caxial hydroxyl groups of lincomycin occurs more readily than between the trans diequatorial 2-and 3-hydroxyl groups. In general, acyl migration occurs faster than hydrolysis where the slowest migration step is about an order of magnitude greater than the fastest hydrolysis step, The fourth possible monoester, lincomycin-7-hexanoate, undergoes straightforward hydrolysis in alkali to lincomycin and hexanoic acid.
Keyphrases 0 Lincomycin monoesters-kinetics of alkaline isomerization and hydrolysis Isomerization rate constants-2-, 3-, and 4-monohexanoates of lincomycin, alkaline media C: Hydrolysis rate constants-2-, 3-, and Cmonohexanoates of lincomycin, alkaline media