Action of Carbon Dioxide on 6-Amino-penicillanic Acid

Abstract

THE nucleus of the penicillin molecule, 6-aminopenicillanic acid (I)¹, is in some respects more stable than most penicillins (II), being, for example, only slowly destroyed by mineral acids. It was therefore surprising to find that carbon dioxide, which is without effect on penicillins, readily attacked 6-aminopenicillanic acid to yield a product which could no longer be converted into penicillins by acylation. The effect was first observed when 6-aminopenicillanic acid was dissolved in water by neutralization with sodium bicarbonate, but a solution of sodium 6-aminopenicillanate in aqueous sodium bicarbonate was much more stable, indicating that the reaction required free carbon dioxide. When carbon dioxide was bubbled continuously through an aqueous solution of 6-aminopenicillanic acid at 37° C. and an initial pH of 7.0 the 6-aminopenicillanic acid content, determined by phenylacetylation followed by biological assay, fell by 50 per cent every 3 hr. The hydroxylamine assay² and the leucine equivalent as determined by ninhydrin fell at the same rate, indicating that both the (β-lactam ring and the amino-group were absent from the reaction product.