Asymmetric Synthesis of Strychnos and Aspidosperma Alkaloids

马钱子和石子生物碱的不对称合成

• 批准号: 1362461
• 负责人: Rodrigo Andrade
• 金额: $ 39万
• 依托单位: Temple University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1362461&HistoricalAwards=false
• 关键词: Asymmetric; Synthesis; Strychnos; Aspidosperma; Alkaloids

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.

获奖摘要在这个由化学系化学合成项目资助的项目中，罗德里戈教授B。坦普尔大学（化学系）的安德拉德正在研究开发新的化学反应，以快速构建复杂的含氮分子。 首要目标是通过最小化合成步骤的总数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是生物活性的，并且可以用于分子生物学以理解生物化学途径，或者直接应用于医学以在分子水平上更好地理解疾病。 然后，化学见解可以应用于治疗方案。 为了测试这些新方法的范围，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，包括那些代表性不足的群体，正在接受复杂分子合成学科的培训。本项目系统地研究并应用了一种新的多米诺Michael/Mannich [4+2]成环方法来合成复杂分子。 在目标1中，正在检查该方法的亲核和亲电组分以确定反应范围。 目的2：将该方法应用于Aspidospermanan型生物碱（+）-epi-condylfoline，（+）-condylfoline，（+）-lagunamine，（+）-epi-lagunamine，（+）-condylocarpine，（+）-isocontylocarpine和（+）-tubotaiwine的不对称全合成。 目的三：利用该方法开展了双-Aspidosperma生物碱（-）-conophylline和（-）-conophyllidine的不对称全合成。