Synthesis and structure-activity studies of antibacterial oxazolidinones containing dihydrothiopyran or dihydrothiazine C-rings

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3475-8. doi: 10.1016/j.bmcl.2006.03.104. Epub 2006 Apr 27.

Abstract

A new series of antimicrobial oxazolidinones bearing unsaturated heterocyclic C-rings is described. Dihydrothiopyran derivatives were prepared from the saturated tetrahydrothiopyran sulfoxides via a Pummerer-rearrangement/elimination sequence. Two new synthetic approaches to the dihydrothiazine ring system were explored, the first involving a novel trifluoroacetylative-detrifluoroacetylative Pummerer-type reaction sequence and the second involving direct dehydrogenation of tetrahydrothiopyran S,S-dioxide intermediates. Final analogs such as 4 and 13 represent oxidized congeners of recent pre-clinical and clinical oxazolidinones.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Positive Bacteria / drug effects*
  • In Vitro Techniques
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Oxazolidinones / chemical synthesis*
  • Oxazolidinones / chemistry
  • Oxazolidinones / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Oxazolidinones