Acidic and alkaline isomerization and hydrolysis of lincomycin monoesters

Abstract

In alkaline media the 2-, 3-, and 4-monohexanoates of lincomycin rapidly isomerize, each entering into facile equilibrium with the other two, with accompanying hydrolysis of each species to lincomycin. In acid media, lincomycin 3-hexanoate and 4-hexanoate isomerize to form a mixture of 3- and 4-hexanoates and a trace of the 2-hexanoate, with accompanying hydrolysis to lincomycin. Lincomycin 2-hexanoate, however, does not isomerize under these conditions and undergoes straightforward hydrolysis. Lincomycin 7-hexanoate undergoes straightforward hydrolysis at low or high pH to form lincomycin and hexanoic acid. Based on the time required for one-half of the initial compound to disappear, the relative alkaline stability of the four monoesters is 3<4<2<<7-hexanoate. Based on the time required for one-half of the total possible lincomycin to appear, the relative order of alkaline stability is 2<3 = 4<<7-hexanoate. In acidic media, based on the time required for one-half of the initial compound to disappear or the time required for one-half of the total possible lincomycin to appear, the relative order of stability is the same, 2 = 3 = 7<4-hexanoate.