关键词: 噻吗洛尔, R-噻吗洛尔, &beta, -受体阻断剂, 光学拆分

Abstract: The S- and R-timblol were prepared by optical resolution of racemic timolol. Thus, the treatment of glycerol with HCl afforded 3-chloro-l,2-propanediol(1). 1 undergoes condensation with tertiary butylamine to give dl-3-t-butylamino-1, 2-propanediol(2) in 70.9% yield. The treatment of 2 with benzaldehyde afforded the oxazolidine derivative(3) in 79% yield. Racemic timolol(4) could be obtained in 53% yield from 3 by treatment with 3-chloro-4-morpholino-1,2,5-thiadiazole and t-BuOKin t-BuOHand hydrolization. 4 is resolved with d-tartaric acid to give S-timolol-d-tartaric acid . salt and R-timolol-d-tartaric acid salt. Then the treatment of these salts with NaOHand maleic acid afforded S-timolol and R-timolol maleate, respectively.

Key words: Timolol, R-Timolol, β-adrenoceptor blocker, Optical resolution