Optical resolution and absolute configuration of a nonsteroidal antiinflammatory drug, 2-(10,11-dihydro-10-oxodibenzo- [b,f]thiepin-2-yl)propionic acid.
The title compound (+/-)-1 (CN-100) was efficiently resolved into a pair of enantiomers by fractional crystallization of the diastereomeric salts of (-)- and (+)-phenylethylamine. The purity of the enantiomers was determined using the chiral cellulose column (CHIRALCEL OJ) which was allowed direct separation of the enantiomers. A separation factor (alpha) of 1.73 was obtained. X-Ray crystallographic analysis of the (+)-isomer [salt of (-)-1-(4-bromophenyl)ethylamine] showed that this enantiomer has S-configuration. Biological studies have shown that only the (+)-isomer has antiinflammatory activity. Racemizaiton of (-)-isomer was carried out by heating its propionic acid solution in the presence of mineral acid, such as HBr.
Yamamoto
M
M
Department of Applied Chemistry, Saitama University, Japan.
Masaki
M
M
Nohira
H
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001582:Benzothiepins / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use; D004285:Dogs; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001582:Benzothiepins; C051758:CN 100