Synthesis of Lobeline, Lobelane and their Analogues. A Review.
Synthesis of Lobeline, Lobelane and their Analogues. A Review.
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DOI：
10.1080/00304948.2015.1066642
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发表时间：
2015
影响因子：
1.5
通讯作者：
Crooks PA
中科院分区：
文献类型：
--
作者：
Zheng G;Crooks PA
（-）-半边莲碱（1）（2 R，6S，10 S-，图1）是半边莲的主要生物碱成分，半边莲是一种原产于北美的植物，作为天然药物有着悠久的历史。这种植物也被称为印第安烟草，因为美洲原住民吸食干叶作为烟草的替代品。1洛贝林的显著药理学特征已在许多研究中得到证实，特别是在药物滥用和神经系统疾病的研究领域。2-5我们实验室的神经化学和行为学研究表明，洛贝林对精神兴奋剂滥用的影响是通过抑制囊泡单胺转运体2（VMAT 2）。2在神经药理学研究中，与洛贝林相比，洛贝林的“脱氧”衍生物洛贝林（2，图1）已被证明是更特异的VMAT 2抑制剂。6，7洛贝兰在减少大鼠的甲基苯丙胺自我给药方面也具有行为活性，8验证了VMAT 2作为治疗甲基苯丙胺滥用的治疗靶点。近年来，人们设计并合成了大量的洛贝林/洛贝烷类似物，并对其构效关系（SAR）进行了综述。5本综述总结了（2005-2014年）洛贝林、洛贝林及其结构相关类似物的合成。
(-)-Lobeline (1)(2R, 6S, 10S-, Fig. 1) is the major alkaloidal constituent of Lobelia inflata, a plant native to North America with a long history of use as a natural remedy. The plant is also called Indian tobacco because Native Americans smoked the dried leaves as a substitute for tobacco. 1 The remarkable pharmacological profile of lobeline has been demonstrated in numerous studies, especially in the research areas of substance abuse and neurological disorders. 2–5 Neurochemical and behavioral studies from our laboratories have suggested that the effect of lobeline on psychostimulant abuse is through inhibition of the vesicular monoamine transporter 2 (VMAT2). 2 In neuropharmacolgical studies, lobelane (2, Fig. 1), a “des-oxygen” derivative of lobeline, has been demonstrated to be a more specific VMAT2 inhibitor compared to lobeline. 6, 7 Lobelane is also behaviorally active in decreasing methamphetamine self-administration in rats, 8 validating VMAT2 as a therapeutic target for the treatment of methamphetamine abuse. A number of lobeline/lobelane analogues have been designed and synthesized and the structureactivity relationships (SAR) of these analogues has been reviewed recently. 5 The present review summarizes (2005–2014) the synthesis of lobeline, lobelane and structurally related analogues.