New methods for the synthesis of spirocyclic cephalosporin analogues

Alan X. Zhao, Louise E. Horsfall, Alison N. Hulme*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Spiro compounds provide attractive targets in drug discovery due to their inherent threedimensional structures, which enhance protein interactions, aid solubility and facilitate molecular modelling. However, synthetic methodology for the spiro-functionalisation of important classes of penicillin and cephalosporin β-lactam antibiotics is comparatively limited. We report a novel method for the generation of spiro-cephalosporin compounds through a Michael-type addition to the dihydrothiazine ring. Coupling of a range of catechols is achieved under mildly basic conditions (K2CO3, DMF), giving the stereoselective formation of spiro-cephalosporins (d.r. 14:1 to 8:1) in moderate to good yields (28−65%).

Original languageEnglish
Article number6035
Issue number19
Early online date5 Oct 2021
Publication statusE-pub ahead of print - 5 Oct 2021

Keywords / Materials (for Non-textual outputs)

  • Michael-type reaction
  • Spiro-cephalosporin
  • Spiro-cyclisation


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