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De Novo Asymmetric Synthesis of Natural and Unnatural Carbohydrate Motifs

天然和非天然碳水化合物基序的从头不对称合成

基本信息

批准号：
1565788
负责人：
George ODoherty
金额：
$ 45万
依托单位：
Northeastern University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2020-04-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1565788&HistoricalAwards=false
关键词：
De Novo Asymmetric Synthesis Natural

项目摘要

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor George O'Doherty. Professor O'Doherty is a faculty member in the Department of Chemistry and Chemical Biology at Northeastern University. He and his group are working to develop practical synthetic approaches to oligo-cyclitols. Cyclitols are structural mimics of carbohydrates that are resistant to metabolism. In contrast to the other biological polymers (e.g., DNA and proteins), there are no practical methods for the construction of stable analogues of the oligosaccharides. To address this need, the O'Doherty group is developing a novel method of monomer assembly to prepare oligo-cyclitols. The O'Doherty group is uniquely positioned to carry out this research, as this project is based on their previously established method for the synthesis of oligosaccharides. The project provides access to novel structures for biological studies. In addition, the research program offers an excellent opportunity to train undergraduate and graduate students, as well as postdoctoral associates in the state of the art methods for complex molecule synthesis. This program impacts society at numerous levels: making carbohydrate synthesis greener, improving drug discovery, and furthering student training. This research has the potential to revolutionize the way oligosaccharide structures are used in medicinal and biological chemistry studies. While methods for exo-C-glycosides syntheses have been developed, the impracticality of these syntheses has limited their use in medicinal chemistry studies. Dr. O'Doherty's approach to cyclitols (aka, endo-C-glycosides or 5a-carbasugars), mirrors the broadly successful approach to oligosaccharides, both of which rely on the use of enantio- and diastereo-selective catalytic reactions (e.g., transition metal or bimetallic catalyzed allylation). The de novo approaches start with a significantly simplified structure and sequentially increases its stereochemical and functional complexity to a range of structures, which in turn enables medicinal chemistry and chemical biology structure-activity relationship studies. This program impacts society at numerous levels: making carbohydrate synthesis greener, improving drug discovery, and furthering student training.

化学部化学合成计划支持乔治·奥多尔蒂教授的项目。O‘Doherty教授是东北大学化学和化学生物学系的一名教员。他和他的团队正在努力开发实用的低聚环醇合成方法。Cyclitol是碳水化合物的结构模拟物，可抵抗新陈代谢。与其他生物聚合物(如DNA和蛋白质)相比，目前还没有实用的方法来构建稳定的寡糖类似物。为了满足这一需求，O‘Doherty小组正在开发一种新的单体组装方法来制备低聚环醇。O‘Doherty团队具有开展这项研究的独特优势，因为该项目基于他们先前建立的低聚糖合成方法。该项目为生物学研究提供了获得新结构的途径。此外，该研究计划提供了一个极好的机会来培训本科生和研究生，以及博士后助理，学习最先进的复杂分子合成方法。这一计划对社会产生了多个层面的影响：使碳水化合物合成更加绿色，改进药物发现，以及进一步培训学生。这项研究有可能彻底改变低聚糖结构在药物和生物化学研究中的使用方式。虽然胞外碳苷的合成方法已经开发出来，但这些合成方法的不切实际限制了它们在药物化学研究中的应用。O‘Doherty博士对环醇(又名内切-C-糖苷或5a-碳糖)的方法反映了低聚糖的广泛成功方法，这两种方法都依赖于对映体和非对映选择性催化反应的使用(例如，过渡金属或双金属催化的烯丙化反应)。从头开始的方法从显著简化的结构开始，然后将其立体化学和功能复杂性增加到一系列结构，这反过来又使得药物化学和化学生物学构效关系的研究成为可能。这一计划对社会产生了多个层面的影响：使碳水化合物合成更加绿色，改进药物发现，以及进一步培训学生。