Continuous Flow Silyl Ether Exchange Methodologies to Achieve Site-Specific Functionalization of Polydroxylic Natural Products

有了这个奖项，NSF化学部的化学合成计划资助了Jacquelyn Gervay-Hague教授的研究，他正在开发有效的连续流动方法，以使多羟基天然产物（如糖）发生特定的变化。连续流动化学是一种将反应物混合在一起进入管中的过程，允许在精确控制的条件下发生化学反应，其中可以调节许多反应条件。这种方法在化学工业中的重要性日益增加，它用于多步工艺，从而有效生产药物和其他增值化学品。通过该技术提供的仔细的实验控制，反应条件如温度、压力和反应时间导致化学结构和反应性之间的新关系，这在传统的“一锅法”化学合成中是观察不到的。参与这项研究的学生正在研究复杂的化学反应，为他们提供机会来表达自己的创造性设计，使天然产品。使用核磁共振（NMR）光谱作为预测化学反应性的主要工具，可以进一步了解化学键的性质及其固有的反应性。该研究为博士和硕士研究生提供了一个肥沃的学习平台，通过在先进制造业的学术，创业和工业环境中的有酬就业，开展有益于社会的科学事业。该研究的智力价值集中在将成功的批量化学转化为连续流动反应，以提高选择性，化学多样性和生产力，并改善安全指标。重要的是，微尺度分段流动技术提供了对产品形成的快速评估，并使连续流动优化成为未来自动化的基础。区分看似等同的羟基以实现特定功能化的能力是化学合成开发的主要挑战。通常，需要几个保护和脱保护步骤，这增加了生产时间并降低了步骤经济性。此外，许多程序需要合成专业知识，这限制了化学合成竞技场以外的科学家的参与。包括肽和核酸合成仪在内的自动化合成平台已被非专家广泛采用，并改变了化学生物学研究。增加生物医学研究人员获得天然产物类似物的机会在最近的国家科学院关于糖科学未来的出版物中被宣布为首要任务。该研究开发了连续流方法，用于将甲硅烷基醚转化为酯，醚和醇等替代功能。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。

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is funding the research of Professor Jacquelyn Gervay-Hague who is developing efficient continuous flow methods to make site-specific changes of polyhydroxylic natural products, such as sugars. Continuous flow chemistry is a process in which reactants are mixed together into tubes allowing a chemical reaction to occur under precisely controlled conditions where numerous reaction conditions can be adjusted. This method is of increasing importance in the chemical industry where it is used in multi-step processes leading to the efficient production of pharmaceuticals and other value-added chemicals. With the careful experimental control offered by this technology, the reaction conditions such as temperature, pressure, and reaction time result in new relationships between chemical structure and reactivity that are not observable in traditional "one-pot" chemistry synthesis. Students involved in this research are investigating complex chemical reactions providing them the opportunity to express their own creative design of making natural products. The use of Nuclear Magnetic Resonance (NMR) spectroscopy as a major tool for predicting chemical reactivity gives further insight into the nature of chemical bonds and their inherent reactivity. This research provides a fertile learning platform for both doctoral and masters graduate students to launch scientific careers that benefit society through gainful employment in academic, entrepreneurial, and industrial settings in advanced manufacturing.The intellectual merit of the research focuses on transferring successful batch chemistries to continuous flow reactions to increase selectivity, chemical diversity, and productivity with improved safety metrics. Importantly, microscale segmented flow techniques provide rapid assessment of product formation and enable continuous flow optimization as a basis for future automation. The ability to differentiate between seemingly equivalent hydroxyl groups in order to achieve specific functionalization is a major challenge for chemical synthesis development. Typically, several protection and deprotection steps are required, which increases production time and decreases step economy. In addition, many of the procedures require synthetic expertise, which limits accessibility to scientists outside the chemical synthesis arena. Automated synthesis platforms including peptide and nucleic acid synthesizers have been widely adopted by non-experts and have transformed chemical biology research. Increasing access of natural product analogs to biomedical researchers was proclaimed a top priority in a recent National Academy of Sciences publication on the future of glycosciences. This research developes continuous flow methodologies for site-specific conversion of silyl ethers to alternative functionalities such as esters, ethers, and alcohols.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.