光学纯(R)-3-奎宁醇制备技术研究进展

Research progress in the preparation of optical pure(R)-3-quinuclidinol

抗胆碱能药是一类阻滞乙酰胆碱与胆碱受体相结合的药物,可用于阿尔茨海默病、慢性阻塞性肺病以及尿失禁等多种疾病的治疗.(R)-3-奎宁醇是制备新型抗胆碱能药的关键手性中间体.目前已报道了该手性中间体的多种合成方法,如化学拆分法、化学不对称催化法、酶法拆分以及生物不对称还原法等,其中采用生物不对称还原法制备(R)-3-奎宁醇的产量已达千克级.主要综述了(R)-3-奎宁醇的化学合成法和生物合成法,重点介绍了生物催化不对称还原法制备(R)-3-奎宁醇的研究进展.

Anticholinergics are a kind of drugs that block the combination of acetylcholine with cholinergic receptors,and used for the treatment of a variety of diseases,such as Alzheimers disease,chronic obstructive pulmonary disease and urinary incontinence.（R）-3-quinuclidinol is a key chiral intermediate for numerous new anticholinergics.Up to now,several synthetic methods for this chiral intermediate have been reported,such as chemical resolution,chemical asymmetric catalysis,enzymatic resolution and biological asymmetric reduction.Remarkably,synthesis of（R）-3-quinuclidinol by biological asymmetric reduction has reached kilogram grade.Synthetic routes of（R）-3-quinuclidinol were reviewed in this paper,and the emphasis was focused on biocatalytic asymmetric reduction.