Abstract
The 6,6-dibromopenam (6) was treated with CH3MgBr and carbaldehyde5 to afford the hydroxy compound7, which was reacted with acetic anhydride to give acetoxy compound8. The deacetobromination of8 with zinc and acetic acid gave 6-exomethylenepenams,E-isomer10 andZ-isomer9, which was oxidized to sulfone11 bym-CPBA. Thep-methoxybenzyl compounds were deprotected by AlCl3 and neutralized to give the sodium salts12, 13 and14.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References Cited
Bennett, I. S., Brooks, G., Broom, N. J. P., Calvert, S. H., Coleman, K. and Francois, I., 6-(Substituted methylene) penems, potent broad spectrum inhibitors of bacterial β-lactamase V. Chiral 1,2,3-triazolyl derivatives.J. Antibiotics, 44, 969–978 (1991a).
Bennett, I., Broom, N. J. P., Bruton, G., Calvert, S., Clarke, B. P., Coleman, K., Edmondson, R., Edwards, P., Jones, D., Osborne, N. F. and Walker, G., 6-(Substituted methylene)penems, potent broad spectrum inhibitors of bacterial β-lactamase III. Structure-activity relationships of the 5-membered heterocyclic derivatives.J. Antibiotics, 44, 331–337 (1991b).
Boyer, J. H. and Hamer, J., The acid-catalyzed reaction of alkyl azides upon carbonyl compounds.J. Am. Chem. Soc., 77, 951–954 (1955).
Broom, N. J. P., Brooks, G. and Clark, B. P., β-(Substituted methylene) penems.Eur. Pat. Appl. 321187 A1, (1989).
Chen, Y. L., Chang, C. W. and Hedberg, K., Synthesis of a potent β-lactamase inhibitor 1,1-dioxo-6-(2-pyridyl)methylenepenicillanic acid and its reaction with sodium methoxide.Tetrahedron Lett., 27, 3449–3452 (1986).
Chen, Y. L., Chang, C. W., Hedberg, K., Guarino, K., Welch, W. M. and Kiessling, L., Structure-activity relationships of 6-(heterocyclyl)methylene penam sulfones; a new class of β-lactamase inhibitors.J. Antibiotics, 40, 803–822 (1987).
English, A. R., Retsema, J. A., Girard, A. E., Lynch, J. E. and Barth, W. E., CP-45,899, a β-lactamase inhibitor that extends the antibacterial spectrum of β-lactams; initial bacteriological characterization.Antimicrob. Agents Chemother., 14, 414–419 (1978).
Kapur, J. C. and Fasel, H. P., 6,6-Dibromopenicillanic acid 1,1-dioxide.Eur. Pat. Appl. EP 139047, (1985).
Micetich, R. G., Maiti, S. N., Spevak, P., Hall, T. W., Yamabe, S., Ishida, N., Tanaka, M., Yamazaki, T., Nakai, A. and Ogawa, K., Synthesis and β-lactamase inhibitory properties of 2β-[(1,2,3-triazol-1-yl)methyl]-2α-methylpenam-3α-carboxylic acid 1,1-dioxide and related triazolyl derivatives.J. Med. Chem., 30, 1469–1474 (1987).
Reading, C. and Farmer, T., The inhibition of β-lactamases from gram-negative bacteria by clavulanic acid.Biochem. J., 199, 779–787 (1981).
Sauer, J. C., Propiolaldehyde.Org. Synthesis, 4, 813–815 (1963).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Im, C., Oh, J.S. & Yim, C.B. Synthesis of 6-exomethylenepenams as β-lactamase inhibitors. Arch Pharm Res 22, 68–71 (1999). https://doi.org/10.1007/BF02976438
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02976438