Automation of Neoglycoside Synthesis

描述（由申请人提供）：Thorson及其同事开发的小分子和天然产物糖基化过程已被验证为小分子和大分子治疗中第一个简单，有效和通用的糖基化策略之一。鉴于其广泛的实用性和对改善药物先导物的特异性、机制和ADME特性的文献影响，糖随机化技术平台有望彻底改变药物发现的未来。Centrose， LLC是一家基于该技术平台的公司，将使用glycordonization和neglycordonization专利技术开发突破性产品来治疗癌症，并预计未来将扩展到传染病市场。通过自动化进一步加速和简化革命性糖随机化过程的能力将从根本上增强糖随机化对未来药物发现的影响。第一阶段SBIR提案专门针对PA-06-012（医疗，牙科和生物技术的制造工艺；SBIR R43/R44），并提出了一种系统的方法来开发原型（指定为“糖colator”），用于全自动新糖随机化药物发现。在第一阶段的早期时间表中，我们特别寻求描述与我们选择的自动化平台- Gilson GX-271 ASPECTM兼容的最佳反应溶剂，反应加热，反应混合和产品纯化参数。然后，这些元素将被组合成第一个全自动的“糖醇化器”，并在后期的I期时间表中专门用于评估糖醇化器在文库建设和代表性新糖苷制备规模合成中的效用。作为一项潜在的未来II期研究，我们设想扩展这个自动化平台，包括自动化上游单糖化学和自动化下游化学选择连接化学，这两者都有望大大增强糖随机化药物发现技术平台的竞争优势。

DESCRIPTION (provided by applicant): The process of small molecule and natural product glycorandomization developed by Thorson and coworkers has been validated as one of the first simple, efficient and general glycosylation strategies for small molecule and macromolecular therapeutics. Given its broad utility and documented impact on improving the specificity, mechanism and ADME properties of drug leads, the glycorandomization technology platform is expected to revolutionize the future of drug discovery. Centrose, LLC, a company based upon this technology platform, will use the patented glycorandomization and neoglycorandomization technologies to develop breakthrough products to treat cancer with an anticipated future expansion into the infectious disease market. The ability to further accelerate and simplify the revolutionary glycorandomization process via automation will radically enhance the impact of glycorandomization upon the future of drug discovery. This phase I SBIR proposal specifically targets PA-06-012 (Manufacturing Processes of Medical, Dental, and Biological Technologies; SBIR R43/R44) and presents a systematic approach toward the development of a prototype (designated the `glycolator') for fully-automated neoglycorandomization drug discovery. Within the early Phase I timeline, we specifically seek to delineate the best reaction solvent, reaction heating, reaction mixing and product purification parameters compatible with our selected automation platform - the Gilson GX-271 ASPECTM. These elements will then be combined as the first fully automated `glycolator' and the later Phase I timeline specifically dedicated to assessing the utility of the glycolator for both library construction and preparative scale synthesis of representative neoglycosides. As a potential future Phase II study, we envision an expansion of this automated platform to encompass both automated upstream monosaccharide chemistries and automated downstream chemoselective ligation chemistries - both of which are anticipated to greatly enhance the competitive advantage of the glycorandomization drug discovery technology platform.