Enzymatic optical resolution of dibenzoxepins and its application to an optically active antiallergic agent with thromboxane A2 receptor antagonistic activity.
Methyl (+/-)-11-(2-hydroxyethyl)thio-6,11-dihydrodibenz[b,e]oxepin- 2- carboxylate (5) was enantio-selectively acylated with acetic anhydride in an organic medium by Lipase Amano P to give methyl (-)-11-(2-acetoxyethyl)thio-6,11-dihydrodibenz[b,e]oxepin-2- carboxylate (8), and the (+)-enantiomer by Lipase Sigma Type VII. Using Lipase Amano P, (+)- and (-)-(5) could be prepared with high optical purity (84-94% e.e.). These products were respectively converted to (+)- and (-)-KW-4099, which had antiallergic activity with complete retention of the optical purity.
Kuge
Y
Y
Sakai Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Osaka, Japan.
Shioga
K
K
Sugaya
T
T
Tomioka
S
S
D000215:Acylation; D002851:Chromatography, High Pressure Liquid; D003990:Dibenzoxepins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D003990:Dibenzoxepins; D010880:Piperidines; D017482:Receptors, Thromboxane; C074371:KW 4099; D013928:Thromboxane A2