Asymmetric Synthesis of Alkaloids Enabled by Novel Methodology

化学学部化学合成项目支持Rodrigo B. Andrade教授的项目。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，以快速生成复杂的含氮分子。他的首要目标是利用实验室中发现的新试剂和反应，最大限度地提高复杂的三维分子的制备效率。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，因此它们可以被用作分子探针，以更好地了解生化途径或用作医学上的治疗方法。除了培养本科生和研究生（包括那些来自代表性不足群体的学生）之外，该项目还涉及有机化学（如全合成、合成方法学）、化学生物学、分子生物学、生物化学和医学等领域。n -亚砜基金属二胺（NSMDs）已成为一种强大的不对称合成子。该项目的重点是确定无环nsmd与各种亲电试剂的反应机制和范围，这在逻辑上是建立在先前对芳烃融合同系物的研究基础上的。具体来说，在Aim 1中，研究人员正在研究无环nsmd与亲电烯烃通过Domino Michael/Mannich（正式Diels-Alder）过程生成环加合物的反应范围。在Aim 2中，研究小组将Aim 1确定的最佳反应条件应用于步进高效、不对称的复杂Iboga生物碱(+)-catharanthine、(+)-coronaridine和(+)-ibogamine的全合成。在Aim 3中，研究学生系统地研究了nsmd与醛（葡萄醛）和亚胺（葡萄曼尼希）的反应。在Aim 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功能化的n -亚砜基亚胺，这些亚胺可以进一步修饰以获得用于有机合成的手性构建块。所有的力学分析都使用计算机建模。Andrade教授在他的研究活动中表现出了将本科生，特别是来自代表性不足群体的本科生纳入其中的坚定承诺。

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.