YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
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Synthesis of 6-Exomethylene Penam Derivatives with Triazole Ring

트리아졸환 함유 6-엑소메칠렌 펜남 유도체의 합성

  • 임채욱 (중앙대학교 약학대학 의약화학 교실) ;
  • 오정석 (중앙대학교 약학대학 의약화학 교실) ;
  • 임철부 (중앙대학교 약학대학 의약화학 교실)
  • Published : 2001.04.01
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Abstract

The synthesis of new 6-exomethylene penams with triazole ring for $\beta$-lactamase inhibitor was described. The 6,6-dibromopenam 6 was treated with $CH_3$MgBr and carbaldehyde 5 to afford the 6-bromo-6-(1-hydroxy-1-methyl)penicillanate 7, which was reacted with acetic anhydride to give acetoxy compound 8. The deacetoxybromination of 8 with zinc and acetic acid gave 6-exomethylenepenams, Z-isomer 9 and E-isomer 10, which were oxidized to sulfones 11 and 12 by m-CPBA. The p-methoxybenzyl compounds 9~12 were deprotected by AIC1$_3$and neutralized to give the sodium salts 13~16.

Keywords

References

  1. Science v.257 The crisis in antibiotic resistance Neu, H.C.
  2. Antimicrob. Agents Chemother. v.11 A β-lactanse-inhibiting β-lactam from Streptomyces clavuligerus Reading, C.;Cole, M.
  3. Antimicrob. Agents Chemother. v.14 CP-45,899,a β-lactamase inhibitor that extends the antibacterial spectrum of β-lactams;initial bacteriological characterization English, A. R.;Retsema, J. A.;Girard, A. E.;Lynch, J. E.;Barth, W. E.
  4. J .Med. Chem. v.30 Synthesis and β-lactamase inhibitory properties of 2β-[(1,2,3-triazol-1-yl)me-thyl]-2α-methylpenam-3α-carboxylic acid 1,1- dioxide and related triazolyl deribatives Micetich, R. G.;Maiti, S. N.;Spevak, P.;Hall, T.W.;Yamabe, S.;Ishida, N.;Tanaka, M.;Yamazaki, T.;Nakai, a.;Ogawa, K.
  5. J. Antibiotics v.44 6-(Substituted methylene)penems, potent broad spectrum inhibitors of bacterial β-lactamase Ⅴ.;Chiral 1,2,3-triazolyl derivatives Bennett, I.S.;Brooks, G.;Broom, N.J.P.;Calvert, S.H.;Coleman, K.;Francois, I.
  6. J. Antibiotics v.44 6-(Substituted methylene)penems, potent broad spectrum inhibitors of bacterial β-lactamase Ⅲ. ;Structure-activity relationships of the 5-menbered heterocyclic derivatives Bennett, I.S.;Broom, N.J.P.;Bruton, G.;Clavert, S.;Clarke, B.P.;Coleman, K.;Edmondson, R.;Edwards, P.;Johns,D.;Osborne, N.F.;Walker, G.
  7. Eur. Pat. Appl. β-(Substituted methylene) penems Brooms, N.J.P.;Brooks, G.;Clark, B.P.
  8. Tetrahedron Lett. v.27 Synthesis of a potent β-lactamase inhibitor 1,1-dioxo-6-(2-pyridy)methylenepenucillanic acid and its reaction with sodium methoxide Chen, Y. L.;Chang, C. W.;Hedberg, K.
  9. J. Antibiotics v.40 Structure-activity relationships of 6-(heterocyclyl) methylene penam sulfones;a new class of β-lactamase inhibitors Chen, Y.L.;Chang, C.W.;Hedberg, K.;Guarino, K.;Welch, W.M.;Kiissling, L.