CAREER: Carbohydrate Synthesis with Anomeric Nucleophiles

职业：用异头亲核试剂合成碳水化合物

• 批准号: 1753225
• 负责人: Maciej Walczak
• 金额: $ 65万
• 依托单位: University of Colorado at Boulder
• 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: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1753225&HistoricalAwards=false
• 关键词: CAREER; Carbohydrate; Synthesis; Anomeric; Nucleophiles

With this CAREER award, the Chemical Synthesis Program of the NSF Chemistry Division supports the research of Professor Maciej Walczak in the Department of Chemistry at the University of Colorado in Boulder. Professor Walczak and his students develop new methods to make carbohydrates. Carbohydrates, the most abundant biopolymers, are involved in energy storage in the body. They also control molecular recognition events in the body. This research develops versatile methods for the synthesis of bioactive glycosides and glycopeptides. This research enables comprehensive studies on the function of carbohydrates in biology, and facilitates the preparation of high-value biological compounds and pharmaceutical agents. The synthetic approaches specifically enable the preparation of anti-diabetic drugs and anti-tumor antibiotics. Professor Walczak's group is well positioned to educate and train students from groups that are underrepresented in science. Outreach activities focus on improving science awareness in the local communities, specifically through education at the high school level and public presentations. The education program integrates efforts at the department and university levels to create a collaborative community of researchers working at the interface of chemistry and biology.This research develops versatile new methodologies for the synthesis of bioactive saccharides, primarily glycosides and glycopeptides. A majority of known methods to synthesize saccharides focus on substrates in which the anomeric position is substituted with an electronegative element. This approach bears several limitations such as substrate dependence, the need for protective group manipulations, and incompatibility with free alcohol groups. The central hypothesis of this NSF CAREER award is that configurationally stable anomeric nucleophiles are engaged in stereospecific (stereoretentive) reactions under transition metal-catalyzed conditions, forming carbon-carbon and carbon-nitrogen bonds with high selectivities. These moieties are independent from the nature of the substrates and catalysts. Capitalizing on these new conceptual foundations, three specific aims are pursued: (a) the development of cross-coupling reactions of anomeric boronic acids, (b) the implementation of new chemical methods for the synthesis of carbon-glycosides, and (c) the development of new methods in the synthesis of nitrogen-linked glycoproteins. Successful realization of these aims yields novel umpolung methods that eliminate the critical problems inherent to the previous approaches. The synthetic approaches also enable the preparation of anti-diabetic drugs, anti-tumor antibiotics, glycoproteins, and glycopeptides under standardized and user-friendly conditions. The research program is also intimately connected with ongoing educational and outreach activities. An undergraduate course featuring blended learning supplemented by randomized trial to improve undergraduate pedagogy is being developed and implemented. The outreach activities focus on mentoring high-school students.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，NSF化学部的化学合成计划支持博尔德科罗拉多大学化学系的Maciej Walczak教授的研究。 Walczak教授和他的学生们开发了制造碳水化合物的新方法。碳水化合物是最丰富的生物聚合物，参与体内的能量储存。 它们还控制体内的分子识别事件。本研究为生物活性糖苷和糖肽的合成开发了多种方法。 这项研究使人们能够全面研究碳水化合物在生物学中的功能，并促进高价值生物化合物和药物制剂的制备。合成方法特别能够制备抗糖尿病药物和抗肿瘤抗生素。 沃尔扎克教授的小组处于有利地位，可以教育和培训来自科学领域代表性不足的群体的学生。外联活动的重点是提高当地社区的科学意识，特别是通过高中教育和公开演讲。该教育计划整合了部门和大学层面的努力，以创建一个在化学和生物学界面工作的研究人员的协作社区。这项研究开发了用于合成生物活性化合物的多功能新方法，主要是糖苷和糖肽。 大多数已知的合成异头化合物的方法集中在其中异头位置被负电性元素取代的底物上。这种方法有几个局限性，如底物依赖性，需要保护基团的操作，以及与游离醇基团的不相容性。这个NSF CAREER奖的中心假设是构型稳定的异头亲核试剂在过渡金属催化条件下参与立体特异性（立体保留）反应，以高选择性形成碳-碳和碳-氮键。 这些部分独立于底物和催化剂的性质。利用这些新的概念基础，追求三个具体目标：（a）异头硼酸的交叉偶联反应的发展，（B）实施新的化学方法合成碳糖苷，和（c）在合成氮连接的糖蛋白的新方法的发展。这些目标的成功实现产生新的umpolung方法，消除了以前的方法固有的关键问题。该合成方法还使得能够在标准化和用户友好的条件下制备抗糖尿病药物、抗肿瘤抗生素、糖蛋白和糖肽。研究计划也与正在进行的教育和推广活动密切相关。目前正在制定和实施一门本科课程，其特点是混合学习，并辅之以随机试验，以改进本科教学法。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Copper-Catalyzed Oxidative Acetalization of Boronic Esters: An Umpolung Strategy for Cyclic Acetal Synthesis

• DOI: 10.1021/acs.joc.0c00720
• 发表时间: 2020-06-19
• 期刊: JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 3.6
• 作者: Miller, Eric M.;Walczak, Maciej A.
• 通讯作者: Walczak, Maciej A.