Lactol Esters of Ampicillin

Several lactol esters of D-α-aminobenzylpenicillin hydrochloride (Va-e) were synthesized from the corresponding lactol esters of benzylpenicillin (IIa-e) or from D-α-aminobenzylpenicillin (ampicillin). The lactol esters IIa-e were prepared with potassium benzylpenicillinate (I) and certain halides of lactols. Among them, two isomers of 2 (5H)-furanone-5-yl benzylpenicillinate (IIb) could be easily separated from the mixture of the stereoisomers due to C5' position of the lactol moiety. We found that all of these lactol esters of ampicillin hydrochloride (Va-e) showed higher blood concentrations of ampicillin after oral administration to rats than that of ampicillin itself. Particularly Va and Ve were much superior.