The mixed anhydride (I), named in the title, which is readily prepared from a salt of benzylpenicillin and ethyl chloroformate, reacts with amines to form amides, with alcohols to form esters, and with thiols for form thiol-esters of the antibiotic. Several of the derivatives so prepared are hydrolysed in aqueous media to liberate free benzylpenicillin, a property that makes them of possible therapeutic interest.
ESTERS of benzylpenicillin have attracted relatively little interest in the past largely becausethe first known members, namely, the simple alkyl and aralkyl esters, were devoid of antibacterial activity both in vitro and in man (though not in mice and rats). Carpenter ( J . Amer. Chem. Soc., 1948, 70, 2964), however, found that the dimethylaminoethyl ester (11; X = -O*CH,*CH,*NMe,) exhibited full activity in the plate bioassay, owing, as he showed, to its ready hydrolysis to free penicillin and the amino-alcohol. More recently the important discovery has been made that the dialkylaminoethyl esters, particularly the hydriodide of the diethylamino-homologe (Estopen), are selectively concentrated in inflamed lung tissue : of these, however, only the last mentioned has been tested on human subjects; it gave rise to prolonged effective levels of penicillin in their sputa (Friederiksen and Nielson, XIIth Internat. Congr.
