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CAREER: Stereoselective Carbene Cascade Cyclizations

职业：立体选择性卡宾级联环化

基本信息

批准号：
1753187
负责人：
Indrajeet Sharma
金额：
$ 65万
依托单位：
University of Oklahoma Norman Campus
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2024-10-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1753187&HistoricalAwards=false
关键词：
CAREER Stereoselective Carbene Cascade Cyclizations

项目摘要

With this CAREER Award, the Chemical Synthesis Program of the Division of Chemistry is supporting the research of Professor Indrajeet Sharma at the University of Oklahoma. Professor Sharma is developing new synthetic methods for the construction of the types of bioactive molecules that are frequently used in efforts to identify drug leads for the treatment of cancer, infectious diseases, and neurological disorders. The research described seeks to develop cascade reactions that take advantage of a sequence of carefully timed steps to convert inexpensive, readily accessible compounds into higher-value, complex molecules. To accomplish this, the Sharma group is developing new reaction protocols that involve the use of more than one metal at a time. This research is expected to have broad application in the fields of chemical synthesis, medicinal chemistry, and therapeutics development. Professor Sharma is also pioneering an outreach program, the Synergistic Catalytic Cycle for Education Excellence (SC2E2), that provides crucial hands-on science education for underrepresented students in the State of Oklahoma. The SC2E2 program encourages an increase in school enrollment, retention, and graduation rates of highly qualified STEM students from low-income areas in the State of Oklahoma.Despite dramatic advances in natural product-inspired drug discovery, many bioactive scaffolds (spirocycles, medium-sized rings, and terpene furanolactones) remain underexploited in drug discovery screening owing to the challenges associated with their synthesis. To address these challenges, this research program will utilize metal carbene cascade reactions for the efficient scalable synthesis of such scaffolds. More specifically, this research focuses on the use of diazo-derived metal-carbenes that are ambiphilic in nature in combination with a second metal catalyst to trigger sequential reactions with a nucleophile and an electrophile. The ensuing cascade reactions lead to the rapid generation of molecular complexity. A comprehensive educational plan is also integrated with the research goals to provide an inclusive scientific education experience for students from underrepresented groups in the State of Oklahoma. The proposed SC2E2 program is inspired from developed research involving synergistic catalysis, in which two or more catalysts act simultaneously to improve the efficiency of existing transformations. Likewise, SC2E2 builds upon inclusive educational practices in a cyclic process by providing students training, guidance and leadership opportunities, which ultimately help cultivate a new generation of diverse STEM professionals.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

有了这个职业奖，化学系的化学合成计划正在支持俄克拉荷马州大学的Indrajeet Sharma教授的研究。 Sharma教授正在开发新的合成方法，用于构建生物活性分子的类型，这些生物活性分子经常用于识别治疗癌症，传染病和神经系统疾病的药物线索。所描述的研究旨在开发级联反应，利用一系列精心计时的步骤将廉价，易于获得的化合物转化为更高价值的复杂分子。为了实现这一目标，Sharma团队正在开发新的反应方案，其中涉及一次使用多种金属。该研究有望在化学合成、药物化学和药物开发等领域有广泛的应用。教授夏尔马还开创了一个外展计划，协同催化循环卓越教育（SC2 E2），提供了重要的动手科学教育，为代表性不足的学生在俄克拉荷马州的状态。SC2 E2项目鼓励俄克拉荷马州低收入地区高素质STEM学生的入学率、保留率和毕业率的提高。尽管天然产物启发的药物发现取得了巨大进展，但许多生物活性支架（螺环、中等大小的环和萜烯呋喃内酯）由于与合成相关的挑战而在药物发现筛选中仍然未得到充分利用。为了解决这些挑战，该研究计划将利用金属卡宾级联反应来有效地合成这种支架。更具体地，本研究集中于使用重氮衍生的金属-卡宾，其在性质上是两亲性的，与第二金属催化剂组合以引发与亲核试剂和亲电试剂的顺序反应。随后的级联反应导致分子复杂性的快速产生。一个全面的教育计划也与研究目标相结合，为来自俄克拉荷马州代表性不足的群体的学生提供包容性的科学教育体验。SC2 E2计划的灵感来自于涉及协同催化的研究，其中两种或更多种催化剂同时起作用，以提高现有转化的效率。同样，SC2 E2通过为学生提供培训、指导和领导机会，在循环过程中建立在包容性教育实践的基础上，最终有助于培养新一代多元化的STEM专业人士。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。