Thienamycin, imipenem and new members of the carbapenem class of β-lactam antibiotics
Thienamycin (Figure 1a) was initially isolated from Streptomyces cattleya and was the first member of the carbapenem class to be characterized. Two observations became immediately obvious. First, its antibacterial spectrum and potency has no equal among either the naturally-occurring or semi-synthetic β-lactam antibiotics (Kropp et al., 1976). Secondly, its structure is equally unique. (1a) is the initial member of a large series of antibiotics having the carbapenem nucleus (2) (Albers-Schonberg et a1., 1978). Also, the two hydrogen atoms at the adjacent 5,6 positions of the bicyclic ring structure are trans rather than the cis configuration found in the penicillins and cephalosporins. Although a sulphur atom is contained in the thienamycin structure, it is appended in the exocyclic cysteamine side chain rather than located within the nucleus itself. However, the most remarkable feature of the structure is the replacement of the conventional amide side chain with the hydroxyethyl group.
KeywordsTotal Synthesis Lactam Antibiotic Tetrahedron Letter Hydroxyethyl Group Amide Side Chain
Unable to display preview. Download preview PDF.
- ALBERS-SCHONBERG, G., ARISON, B.H., HENSENS, O.D., HIRSHFIELD, J., HOOGSTEEN, K., KACZKA, E.A., RHODES, R.E., KAHAN, J.S., KAHAN, F.M., RATCLIFFE, R.W., WALTON, E., RUSWINKLE, MORIN, R.B. & CHRISTENSEN, B.G. (1978). Structure and absolute configuration of thienamycin. J. Am. Chem. Soc., 100, 6491–6499.CrossRefGoogle Scholar
- ASHTON, W.T., BARASH, L., BROWN, J.E., BROWN, R.D., CANNING, L.F., CHEN, A., GRAHAM, D.W.L., KAHAN, F.M., KROPP, H., SUNDELOF, J.G. & ROGERS, E.F. (1980). Z-2-Acylamino-3-substituted propenoates, inhibitors of the renal dipeptidase (Dehydropeptidase-I) responsible for thienamycin metabolism. 20th Intersci. Conf. Antimicr. Agents & Chemoth., New Orleans, La., Abstract 271.Google Scholar
- KAHAN, J.S., KAHAN, F.M., GOEGELMAN, R., CURRIE, S.A., JACKSON, M., STAPLEY, E.O., MILLER, T.W., MILLER, A.K., HENDLIN, D., MOCHALES, S., HERNANDEZ, S., WOODRUFF, H.B. & BIRNBAUM, J. (1979). Thienamycin, a new β-lactam antibiotic. I. Discovery, taxonomy, isolation, and physical properties. J. Antibiot., 32, 1–12.PubMedCrossRefGoogle Scholar
- KROPP, H., KAHAN, F.M., SUNDELOF, J., DARLAND, G. & BIRNBAUM, J. (1976). 15th Intersci. Conf. Antimicr. Agents & Chemoth., Chicago, Ill., Abstract 228.Google Scholar
- LEANZA, W.J., WILDONGER, K.J., HANNAH, J., SHIH, D.H., RATCLIFFE, R.W., BARASH, L., WALTON, E., FIRESTONE, R.A., PATEL, G.F., KAHAN, F.M., KAHAN, J.S. & CHRISTENSEN, B.G. (1981). Structureactivity relationships in the thienamycin series. In Recent Advances in the Chemistry of β-lactam antibiotics, Gregory, G.I. (ed.) pp. 240–254, London: The Royal Society of Chemistry.Google Scholar
- SHIH, D.H., FAYTER, J.A., BAKER, F., CAMA, L.D. & CHRISTENSEN, B.G. (1983). New Synthetic Carbapenem Antibiotics. 1,2,6-Substituted-1-carbapen-2-em-3-carboxylic acid. 23rd Intersci. Conf. Antimicr. Agents & Chemoth., Las Vegas, Nev., Abstract 333.Google Scholar