Asymmetric Synthesis of Strychnos and Aspidosperma Alkaloids

在这个由化学部化学合成计划资助的项目中，天普大学化学系的Rodrigo Andrade教授将应用新的合成方法合成各种复杂的生物碱天然产物。 虽然存在许多制备复杂生物碱的方法，但需要分步高效的不对称方法。 Andrade教授的研究涉及发现和开发新方法，以不对称方式有效和选择性地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道了一种连续的一锅双环化方法，该方法能够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和Aspidosperma生物碱。 生物碱在医学上具有丰富的历史，因为许多合成和半合成药物如纳洛酮是生物碱的结构修饰。 因此，这类分子的更有效的合成方法将对制药工业产生重大影响。 本提案中提出的一些方法也适用于其他类型的分子。 因此，它将影响其他研究领域（例如，生物化学和农业部门），其中需要合成这些分子。 就教育影响而言，该项目将为学生提供出色的培训，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。

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.