Chiral DNA gyrase inhibitors. 2. Asymmetric synthesis and biological activity of the enantiomers of 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H- pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (ofloxacin).
A short and efficient synthesis, starting with (R)- and (S)-alaninol, of the two optical antipodes of the quinolone antimicrobial agent ofloxacin has been devised. Testing in vitro of the products against a range of bacteria and in an assay system incorporating purified DNA gyrase from different bacterial species demonstrates that the S-(-) enantiomer is substantially the more active.
Mitscher
L A
LA
Department of Medicinal Chemistry, Kansas University, Lawrence 66045.
Sharma
P N
PN
Chu
D T
DT
Shen
L L
LL
Pernet
A G
AG
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015242:Ofloxacin; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D059005:Topoisomerase II Inhibitors
D000900:Anti-Bacterial Agents; D010078:Oxazines; D059005:Topoisomerase II Inhibitors; D015242:Ofloxacin