Synthesis and antibacterial activity of lactivicin derivatives

The chemical modification of the 4-acetylamino group on the cycloserine moiety of lactivicin (1a) was carried out. The lactivicin derivatives (1d, k--p and w) having heterocyclic acylamino groups which have been often utilized in beta-lactam antibiotics showed potent antibacterial activities. Ester prodrugs (7a--d) of lactivicin derivatives were also prepared in order to improve the bioavailability on oral administration. The pivaloyloxymethyl (POM) esters (7a and 7b) and 1-ethoxycarbonyloxyethyl (EOE) ester (7c) were found to have slightly improved protective effect in vivo compared with their parent compounds 1c and 1k.