Asymmetric Synthesis of Strychnos and Aspidosperma Alkaloids

天普大学化学系的Rodrigo B. Andrade教授正在研究一种新的化学反应，以快速构建复杂的含氮分子。该项目由化学学部化学合成项目资助。一个首要目标是通过减少合成步骤的总数量来提高制造具有广泛社会影响的复杂分子的效率。绝大多数这样的分子具有生物活性，可以用于分子生物学来了解生化途径或直接应用于医学，以便在分子水平上更好地了解疾病。然后，化学的洞察力可以应用于治疗方案。为了测试这些新方法的适用范围，实验室正在制备几种来自自然界的复杂分子。在这些新方法的开发和应用过程中，本科生和研究生，包括那些来自代表性不足群体的学生，正在接受复杂分子合成学科的培训。本项目系统研究并应用一种新的多米诺Michael/Mannich[4+2]环化方法合成复杂分子。在Aim 1中，对该方法的亲核和亲电组分进行了检查，以确定反应范围。在Aim 2中，将该方法应用于蛛形纲类生物碱(+)-epi-condyfoline、(+)-condyfoline、(+)-lagunamine、(+)-epi-lagunamine、(+)-condylocarpine、(+)-isocondylocarpine和(+)-tubotaiwine的不对称全合成。在Aim 3中，利用该方法进行了双刺藤生物碱(-)-参茶碱和(-)-参茶碱的不对称全合成。

AWARD ABSTRACTIn this project funded by the Chemical Synthesis program of the Chemistry Division, Professor Rodrigo B. Andrade of Temple University (Department of Chemistry) is studying the development of new chemical reactions to quickly build complex nitrogen-containing molecules. An overarching goal is increasing the efficiency of making complex molecules having broad societal impact by minimizing the overall number of synthetic steps. An overwhelming number of such molecules are biologically active, and can be employed in molecular biology to understand biochemical pathways or directly applied in medicine to better understand disease on a molecular level. The chemical insight can then be applied in therapeutic regimes. To test the scope of these new methods, several complex molecules derived from nature are being prepared in the laboratory. During the development and application of these new methods, undergraduate and graduate students, including those from underrepresented groups, are being trained in the discipline of complex molecules synthesis.This project systematically studies and applies a novel domino Michael/Mannich [4+2] annulation method to the synthesis of complex molecules. In Aim 1, the nucleophilic and electrophilic components of the method are being examined to determine the reaction scope. In Aim 2, the method is applied to the asymmetric total syntheses of the Aspidospermatan-type alkaloids (+)-epi-condyfoline, (+)-condyfoline, (+)-lagunamine, (+)-epi-lagunamine, (+)-condylocarpine, (+)-isocondylocarpine, and (+)-tubotaiwine. In Aim 3, the method is used to develop the asymmetric total syntheses of the bis-Aspidosperma alkaloids (-)-conophylline and (-)-conophyllidine.