Asymmetric Synthesis of Alkaloids Enabled by Novel Methodology

化学系的化学合成计划支持罗德里戈B教授的项目。安德拉德安德拉德教授是天普大学化学系的一名教员。 他正在开发新的化学反应，以快速构建复杂的含氮分子。 首要目标是通过使用他实验室中发现的新试剂和反应来最大限度地提高制备复杂三维分子的效率。 这种方法减少了与合成由碳和氮原子组成的复杂分子相关的时间、能量和成本。 许多这样的分子具有生物活性，因此它们可以用作分子探针以更好地了解生物化学途径或用作医学中的治疗剂。 除了本科生和研究生的培训，包括那些来自代表性不足的群体，这个项目的更广泛的影响触及有机化学领域（例如，全合成、合成方法学）、化学生物学、分子生物学、生物化学和医学。 该项目的重点是确定使用非环状NSMD与各种亲电体的反应的机制和范围，这在逻辑上是从以前的努力芳烃稠合同系物建立的。 具体而言，在目标1中，研究人员正在研究非环状NSMD与亲电烯烃的反应范围，以通过Domino Michael/Mannich（正式Diels-Alder）过程提供环加合物。 在目标2中，研究小组将目标1中确定的最佳反应条件应用于复杂Iboga生物碱（+）-长春质碱、（+）-coronaridine和（+）-ibogamine的分步高效、不对称全合成。 在目标3中，研究学生系统地研究了NSMD与醛（乙烯基羟醛）和亚胺（乙烯基曼尼希）的反应。在目标4中，研究人员正在探索NSMD与亲电氧和氮源的反应，以获得α-官能化的N-亚磺酰亚胺，其可以进一步修饰以获得用于有机合成的手性构建单元。 所有的机理分析都使用计算机建模。 安德拉德教授表现出了对本科生，特别是来自代表性不足的群体，在他的研究活动的包容性的坚定承诺。

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Rodrigo B. Andrade. Professor Andrade is a faculty member in the Department of Chemistry at Temple University. He is developing new chemical reactions to quickly build complex nitrogen-containing molecules. The overarching goal is to maximize the efficiency by which complex, three-dimensional molecules are prepared by using new reagents and reactions discovered in his laboratory. Such an approach reduces the time, energy, and cost associated with synthesizing complex molecules composed of carbon and nitrogen atoms. Many such molecules are biologically active, and so they can be employed as molecular probes to better understand biochemical pathways or as therapeutics to be used in medicine. Beyond the training of undergraduate and graduate students, including those from underrepresented groups, the broader impacts of this project touch the fields of organic chemistry (e.g., total synthesis, synthetic methodology), chemical biology, molecular biology, biochemistry, and medicine.N-Sulfinyl metallodienamines (NSMDs) have emerged as powerful asymmetric synthons for chemical synthesis. The focus of this project is to determine both the mechanism and scope of reactions using acyclic NSMDs with a variety of electrophiles, which logically builds from previous efforts on arene-fused congeners. Specifically, in Aim 1 the researchers are studying the scope of the reactions of acyclic NSMDs with electrophilic olefins to afford cycloadducts through a Domino Michael/Mannich (formal Diels-Alder) process. In Aim 2, the research group is applying optimal reaction conditions determined from Aim 1 toward the step-efficient, asymmetric total syntheses of complex Iboga alkaloids (+)-catharanthine, (+)-coronaridine, and (+)-ibogamine. In Aim 3, the research students are systematically investigating the reactions of NSMDs with aldehydes (vinylogous aldol) and imines (vinylogous Mannich). In Aim 4, researchers are probing the reactions of NSMDs with electrophilic oxygen and nitrogen sources to access alpha-functionalized N-sulfinyl imines, which can be further modified to access chiral building blocks for organic synthesis. Computer modeling is used in all mechanistic analyses. Professor Andrade has demonstrated a strong commitment to the inclusion of undergraduates, particularly from underrepresented groups, in his research activities.