I.~Anion exchange chromatographic separation of diastereomers of amino beta-lactam carboxylic acid antibiotics. II.~Cyanogan modification of ribonuclease S salt bridges

Isolation and characterization of a number of novel beta-lactam products resulting from synthesis employing a Leuchs anhydride synthetic strategy in combination with one of a number of amino acids was expedited. Synthesis of these novel beta-lactams in four steps was demonstrated. A method of purification of beta-lactam products resulting from the synthesis has been developed. Ion exchange chromatography employing an acid gradient is suitable for separation of the majority of beta-lactams synthesized from this Leuchs anhydride strategy. Better than 80% of the side products from the synthesis are removed on a single pass through the strong anion exchanger. Infrared spectrophotometry was used to monitor the presence of the cyclic amide function of the beta-lactams. Minimal interference was encountered when obtaining infrared spectra of fractions resulting from ion exchange. These compounds synthesized and isolated from ion exchange, partition, and reverse phase HPLC chromatography gave infrared spectra consistent with their proposed structures. Their classification as novel amino beta-lactam carboxylic acids (ABC's) comes from infrared, mass spectral, and chromatographic data. The ability to inhibit growth of a broad spectrum of classes of gram positive and gram negative bacteria including certain known pathogens as well as the capacity to inhibit a class A beta-lactamase has been demonstrated. Comparison of certain ABC isomers synthesized exhibited beta-lactamase inhibitory properties comparable to inhibitors currently in clinical use. The modification of beta-lactamase by these novel beta-lactams appears to be stable and irreversible. Growth inhibition and beta-lactamase inhibitory activity demonstrated with these novel beta-lactams suggest that various unnatural isomers of the beta-lactam ring can be accommodated in the catalytic site of these enzymes. Four active isomers were isolated from synthesis of 6-aminopenicillanic acid.;A novel matrix and ancillary reagent were discovered for use in Fast Atom Bombardment mass spectral analysis of nonvolatile and unstable compounds. The C-terminal fragment from gastrin peptide hormone try-met-asp-phe gave a molecular ion of the type (M+1) +. The ancillary reagent incorporated in the matrix solution enhanced molecular ion yield 6-fold. Standard D-6-aminopenicillanic and synthetic L-6-aminopenicillanic acids gave molecular ions.