An improved asymmetric synthetic route to a novel triple uptake inhibitor antidepressant (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)-tetrahydro-2H-pyran-4-ol (D-142)
An improved asymmetric synthetic route to a novel triple uptake inhibitor antidepressant (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)-tetrahydro-2H-pyran-4-ol (D-142)
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DOI：
10.1016/j.tetasy.2011.05.012
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发表时间：
2011-05-31
影响因子：
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通讯作者：
Dutta, Aloke K.
中科院分区：
文献类型：
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作者：
Gopishetty, Bhaskar;Gogoi, Sanjib;Dutta, Aloke K.
三重单胺再摄取抑制剂参与了新一代抗抑郁药的开发，其疗效比目前现有的疗法更高。在本文中，我们开发了一种三元单胺再摄取抑制剂 D-142 的替代高效合成路线，从二苯甲烷开始，经过 11 个步骤，总产率为 18.5%。 D-142是我们最近开发的。本合成策略的关键步骤是通过顺式溴中间体从烯烃优先形成溴醇，这在整个合成中引入了显着的效率。此外，我们还开发了一种有效的方法将光学活性中间体二醇回收回所需的手性环氧化物。 (C) 2011 Elsevier Ltd. 保留所有权利。
Triple monoamine reuptake inhibitors have been implicated in the development of a new generation of antidepressants with higher efficacy than the currently existing therapies. In this paper, we have developed an alternative efficient synthetic route for triple monoamine reuptake inhibitor D-142 in 18.5% overall yield in 11 steps starting from diphenylmethane. D-142 was developed by us recently. The key step of the present synthetic strategy is the preferential formation of a bromohydrin from olefin via a cis-bromonium intermediate, which introduced significant efficiency in the overall synthesis. Furthermore, we have developed an efficient way to recycle the optically active intermediate diol back to the desired chiral epoxide. (C) 2011 Elsevier Ltd. All rights reserved.