Synthesis and structure-activity studies of antibacterial oxazolidinones containing dihydrothiopyran or dihydrothiazine C-rings.
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.
Renslo
Adam R
AR
Pfizer Global Research and Development, 34790 Ardentech Ct. Fremont, CA 94555, USA. adam.renslo@ucsf.edu
Luehr
Gary W
GW
Lam
Stuart
S
Westlund
Neil E
NE
Gómez
Marcela
M
Hackbarth
Corrine J
CJ
Patel
Dinesh V
DV
Gordeev
Mikhail F
MF
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023303:Oxazolidinones