Recent advances in the stereoselective synthesis of trans-3,4-disubstituted-piperidines:: applications to (-)-paroxetine
Recent advances in the stereoselective synthesis of trans-3,4-disubstituted-piperidines:: applications to (-)-paroxetine
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DOI：
10.1016/j.tetasy.2008.01.004
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发表时间：
2008-02-06
影响因子：
--
通讯作者：
Zanirato, Vinicio
中科院分区：
文献类型：
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作者：
De Risi, Carmela;Fanton, Giulia;Zanirato, Vinicio
在大量的天然产物中以及在一大类生物活性天然产物中，双胍环系统是关键的结构元件，也经常嵌入被药物化学家认为是特权结构的支架内。因此，制备取代的哌啶的新的立体选择性路线受到广泛关注。综述了反式-3，4-二取代哌啶的不对称合成路线，介绍了（-）-帕罗西汀[（3S，4 R）-4-（4-氟苯基）-3-（3，4-亚甲二氧基苯氧基甲基）哌啶]的取代模式，它是一种众所周知的选择性5-羟色胺再摄取抑制剂（SSRI），在世界范围内用作抗抑郁药。本文主要综述了（-）-帕罗西汀的对映选择性合成路线，（-）-帕罗西汀已成为一个非常受欢迎的合成目标，以测试新方法的效率。还包括一些最近的立体选择性的外消旋化合物的方法。(C)2008爱思唯尔有限公司保留所有权利。
Piperidine ring systems are the key structural elements in a vast array of natural products as well as in a large class of biologically active natural products, being also often embedded within scaffolds recognized as privileged structures by medicinal chemists. Accordingly, new stereoselective routes to substituted piperidines are of widespread interest. An overview of the asymmetric synthetic routes to trans-3 4-disubstituted piperidines, featuring the substitution pattern of (-)-paroxetine [(3S,4R)-4-(4-fluorophenyl)-3-(3,4-methylenedioxyphenoxymethyl)piperidine], a well-known selective serotonin reuptake inhibitor (SSRI) used worldwide as an antidepressant in humans, is presented. This review is mainly focused on the enantioselective routes to (-)-paroxetine, which has become a very popular synthetic target to test the efficiency of new methodologies. Some recent stereoselective approaches to the racemic compound are also included. (C) 2008 Elsevier Ltd. All rights reserved.