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New Methods for the Synthesis of Spirocyclic Cephalosporin Analogues.

ABSTRACT: Spiro compounds provide attractive targets in drug discovery due to their inherent three-dimensional 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%).

SUBMITTER: Zhao AX

PROVIDER: S-EPMC8512572 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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New Methods for the Synthesis of Spirocyclic Cephalosporin Analogues.

Zhao Alan X AX Horsfall Louise E LE Hulme Alison N AN

Molecules (Basel, Switzerland) 20211005 19

Spiro compounds provide attractive targets in drug discovery due to their inherent three-dimensional 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. ...[more]

PMID: 34641579

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