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: 1111558
• 负责人: Rodrigo Andrade
• 金额: $ 36万
• 依托单位: Temple University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1111558&HistoricalAwards=false
• 关键词: Asymmetric; Synthesis; Strychnos; Aspidosperma; Alkaloids

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Rodrigo Andrade of the Department of Chemistry at Temple University will apply novel synthetic methods toward the synthesis of various complex alkaloid natural products. While many methods exist for the preparation of complex alkaloids, there is a need for step-efficient, asymmetric methodology. Professor Andrade's research involves the discovery and development of novel methods to efficiently and selectively prepare complex natural products in an asymmetric manner, which is essential if they are to be employed as chemical probes in molecular biology. Professor Andrade's group recently reported a sequential one-pot bis-cyclization method that has enabled the concise syntheses of several Strychnos alkaloids; this method will be employed in the syntheses of novel Strychnos and Aspidosperma alkaloids. Alkaloids have a rich history in medicine, as many synthetic and semi-synthetic drugs such as Naloxone are structural modifications of alkaloids. Therefore, more efficient synthetic approaches to this class of molecules will have significant impact on the pharmaceutical industry. Some of the methodology developed in this proposal is also applicable to other classes of molecules. Therefore, it will impact other areas of research (e.g., biochemical and agricultural sectors) in which the synthesis of these molecules is needed. In terms of educational impacts, this project will provide excellent training of students, including those from groups historically underrepresented in the sciences.

天普大学化学系的Rodrigo Andrade教授将运用新的合成方法合成各种复杂的生物碱天然产物，该项目由化学学部化学合成项目资助。虽然有许多制备复杂生物碱的方法，但需要一种阶梯高效、不对称的方法。Andrade教授的研究涉及发现和开发新方法，以有效和有选择性地以不对称方式制备复杂的天然产物，如果它们被用作分子生物学中的化学探针，这是必不可少的。Andrade教授的研究小组最近报告了一种连续的一锅双环化方法，该方法可以简洁地合成几种马钱子生物碱；该方法将用于合成新的马钱子生物碱和蛇鞭草生物碱。生物碱在医学上有着丰富的历史，许多合成和半合成药物，如纳洛酮，都是生物碱的结构修饰。因此，对这类分子更有效的合成方法将对制药工业产生重大影响。在这个建议中发展的一些方法也适用于其他种类的分子。因此，它将影响其他需要合成这些分子的研究领域（例如，生化和农业部门）。就教育影响而言，该项目将为学生提供优秀的培训，包括那些来自历史上在科学领域代表性不足的群体的学生。