MEDICINAL CHEMISTRY, CHEMICAL SYNTHESIS, AND MASS SPECTROMETRY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 药物化学。Carlier小组对药物化学的兴趣包括三个领域。首先，他们制备针对疟疾蚊子(冈比亚按蚊)的乙酰胆碱酯酶(AChE)的物种选择性抑制剂。可以将这种化合物部署在驱虫蚊帐上，以防止疟疾在撒哈拉以南非洲的传播。其次，他们使用基于点击化学的发现方法来识别BACE1(β-分泌酶)抑制剂；这种化合物可能对预防阿尔茨海默病有用。最后，他们准备了新的三重再摄取抑制剂来治疗SSRI抵抗型抑郁症。 对映体选择性合成方法。有机锂试剂在有机合成中普遍存在。Carlier小组感兴趣的是开发有机锂化合物和烯醇酸盐的新的立体选择性反应，以及使用计算和多核核磁共振光谱来确定结构和反应路径。最近，他们开发了一条不对称烷基化路线，合成了一类新的(所谓的“季铵”)苯二氮卓类化合物。这项工作的一个关键特征是瞬时非外消旋(“动态手性”)中间体的中间体。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Medicinal Chemistry. The Carlier group's interests in Medicinal Chemistry encompass three areas. First, they prepare species-selective inhibitors of acetylcholinesterase (AChE) targeting the malaria mosquito (Anopheles gambiae). Such compounds could be deployed on insecticide treated nets to prevent malaria transmission in sub-Saharan Africa. Second, they use click-chemistry based discovery methods to identify BACE1 (beta-secretase) inhibitors; such compounds could be to useful to prevent Alzheimer's disease. Finally, they prepare novel triple reuptake inhibitors to treat SSRI-resistant depression. Enantioselective Synthetic Methods. Organolithium reagents are ubiquitous in organic synthesis. The Carlier group is interested in developing new stereoselective reactions of organolithium compounds and enolates, and in using computation and multinuclear NMR spectroscopy to determine structures and reaction pathways. Recently they developed an enantioselective alkylation route to a new class of (so-called "quaternary") benzodiazepines. A key feature of this work is the intermediacy of transiently non-racemic ("dynamically chiral") intermediates.