Nuclear magnetic resonance and circular dichroism of penicillins derived from disubstituted acetic acids

Abstract

N.m.r. and c.d. spectra of some isomeric pairs of penicillins derived from disubstituted acetic acids are reported. For those penicillins which have an aromatic group attached to C-10 empirical correlations are observed between the configuration at C-10 and, (a) the sign of a c.d. band at 200–210 nm, and (b) the chemical shift of the 3-H and methyl protons. These correlations are used to assign the R configuration to the crystalline methyl (3) and ethyl (4) esters of carbenicillin and to the calcium insoluble isomers of carbenicillin (8) and ticarcillin (9). Many of the penicillins show an upfield shift of the methyl protons relative to their position in 6-aminopenicillanic acid (16). This is ascribed to shielding effects of the side-chain aromatic ring produced by folded conformations of the side-chain. For the penicillins (14) and (15) derived from tyrosine, side-chain rotamer proportions calculated from coupling constants are discussed in relation to chemical shifts. Bands at about 230 and 260–280 nm in the c.d, spectra are discussed in comparison with previous c.d. studies of penicillins and the relevant side-chain acids.