CAREER: SusChEM: New Methods for Heterocycle Synthesis via Organic Photoredox Catalysis

在这项由NSF化学部化学合成计划资助的项目中，北卡罗来纳大学教堂山分校的David Nicewicz教授正在开发新的高效化学反应，用于合成具有潜在治疗应用的环状有机小分子。能够吸收可见光的纯有机染料被用作催化剂，从现成的和可再生的化学品中开发出这些新的、广泛适用的合成转化方法。通过与单电子氧化还原化学相关的氧化还原电势的知识，改进了对这些染料和催化剂的适当选择。Nicewicz博士和他的学生正在汇编和标准化有机电化学氧化还原数据，这些数据将成为有机、有机金属和无机化学从业者参考数据的有用概要。该奖项的更广泛影响还包括对莫尔黑德天文馆科学中心的公众宣传。Nicewicz教授与天文馆的工作人员合作，设计和开发了针对中学生的《烹饪化学》。本项目的重点是乳剂、酵母菌和二氧化碳、发酵以及酸和碱的化学反应，让年轻人接触到厨房里容易接触到的化学概念。一种新型的双组分有机光氧化催化剂体系，由吖啶盐和氧化还原活性氢原子供体组成，使几类新的杂环形成转化成为可能。用这种方法合成的杂环包括环醚、内酯、吡咯烷和内酰胺，以及不饱和醇、羧酸、胺和酰胺等丰富的化学原料，而不需要进行预官能化。这种不含金属的双催化剂系统为合成有机化学的实践者提供了新的工具。在这项建议中开发的新反应技术被应用于首次全合成双去甲三萜类化合物Rubriflordilacone B，这是一种已证明具有抗HIV-1活性的分子。

In this project funded by the Chemical Synthesis Program of the NSF Chemistry Division, Professor David Nicewicz of The University of North Carolina at Chapel Hill is developing new and highly efficient chemical reactions for the synthesis of small cyclic organic molecules that have potential applications in therapeutics. Purely organic dyes that harvest visible light are used as catalysts in the development of these new and widely applicable synthetic transformations from readily available and renewable chemicals. The appropriate selection of these dyes and catalysts is improved by knowledge of the redox potentials associated with single electron redox chemistry. Dr. Nicewicz and his students are assembling and normalizing organic electrochemical redox data that will serve as a useful compendium of reference data for practitioners of organic, organometallic and inorganic chemistries. The broader impacts of this award also include public outreach to the Morehead Planetarium Science Center. Professor Nicewicz collaborates with Planetarium staff to design and develop "The Chemistry of Cooking" targeted towards middle school students. The SciVentures Program focuses on the chemistries of emulsions, yeast and carbon dioxide, fermentation, and acids and bases exposing young people to the readily accessible chemistry concepts in the kitchen. A novel two-component organic photooxidation catalyst system comprised of an acridinium salt and redox-active hydrogen atom donor enables several new classes of heterocycle-forming transformations. The classes of heterocycles forged by this method include cyclic ethers, lactones, pyrrolidines and lactams from alkenes and abundant chemical feedstocks such as unsaturated alcohols, carboxylic acids, amines and amides without the need for pre-functionalization. This metal-free dual catalyst system provides new tools to practioners of synthetic organic chemistry. The new reaction technology developed in this proposal is applied to the first total synthesis of the bisnortriterpenoid, rubriflordilactone B, a molecule with documented activity against HIV-1.