RUI: Stereocontrolled Synthesis of Phantasmidine and Analogs

在这个由化学部化学合成计划资助的项目中，印第安纳州州立大学化学和物理系的Richard Fitch教授将开发一种收敛的对映选择性方法，用于合成phantasmidine，一种新的生物碱和潜在的尼古丁受体激动剂，来自厄瓜多尔毒蛙Epipedobates anthonyi。Phantasmidine具有独特的稠合四环结构，包含吡啶、呋喃、吡咯烷和环丁烷环。 环丁烯及其环氧化物和相应的顺式和反式2-氨基环丁醇的改进合成将被开发，其立体化学将控制其余立构中心的安装。 涉及铑催化的卡宾C-H插入的跨环环闭合将用于闭合四环。 这项工作应产生足够量的材料，为全面的生物评价phantasmidine和烟碱受体之间提供初始的结构选择性关系，以帮助选择性生物探针的发展。 将开发的合成方法应适用于其他相关的杂环以及环丁烷基聚合物和其他结构材料的合成。 这些方法和材料可以影响多个化学工业，包括制药，精细化工和聚合物。 更广泛的影响涉及在一个以本科为主的机构培训本科生和博士后研究员。 本科生将参加印第安纳州州立大学的夏季本科生研究体验（SURE）计划，旨在培养学生的研究文化，包括科学中代表性不足的群体。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Richard Fitch of the Department of Chemistry and Physics at Indiana State University will develop a convergent enantioselective method for the synthesis of phantasmidine, a novel alkaloid and a potential nicotinic receptor agonist from the Ecuadoran poison frog Epipedobates anthonyi. Phantasmidine possesses a unique condensed tetracyclic structure incorporating pyridine, furan, pyrrolidine, and cyclobutane rings. An improved synthesis of cyclobutene, its epoxide and the corresponding cis- and trans-2-aminocyclobutanols will be developed, whose stereochemistry will control installation of the remaining stereocenter. A transannular ring closure involving rhodium-catalyzed carbene C-H insertion will be used to close the tetracycle. This work should produce a sufficient amount of material for a full biological evaluation of phantasmidine and provide initial structure-selectivity relationships among nicotinic receptors to aid the development of selective biological probes. The synthetic methodology that will be developed should be applicable to other related heterocycles as well as the synthesis of cyclobutane-based polymers and other structured materials. These methods and materials can impact several chemical industries, including pharmaceuticals, fine chemicals and polymers. The broader impacts involve the training of undergraduate students and a postdoctoral fellow at a predominantly undergraduate institution. The undergraduate students will participate in the Summer Undergraduate Research Experiences (SURE) program at Indiana State University, aimed at fostering a research culture among students including groups underrepresented in the sciences.