The Development of Conveniently Formatted Solid-Supported Reagents for Flow-Based Synthesis

用于流式合成的方便格式化的固相支持试剂的开发

• 批准号: EP/G028125/1
• 负责人: Steven Ley
• 金额: $ 24.32万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG028125%2F1
• 关键词: Development; Conveniently; Formatted; Solid; Supported

The pharmaceutical discovery process is changing rapidly generating a greater need for conduct chemistry in a more efficient and timely fashion. As the global emphasis towards achieving the highest safety standards and sustainable practices unfolds, it is becoming necessary to re-evaluate how chemical synthesis is conducted. In medicinal chemistry in particular the acceleration of cycle times through high-throughput assaying and fast iterative design has put new emphasis on the reliability of processes and compound preparation times. A more integrated and continuous relay of information regarding the ongoing synthesis and its products in terms of basic characterization, physical properties and their functions needs to be captured. These requirements coupled with a desire for flexible synthetic implementation seem ideally suited to a flow-based approach to chemical synthesis. It is therefore our conclusion that future MedChem programmes will make increasing use of flow techniques and many of these will benefit from the use of solid-supported reagents and scavengers.Monoliths have been proposed and developed for use in solid-supported continuous flow synthesis. Monoliths are a single continuous piece of porous material which can be made from either organic or inorganic materials. These monoliths can be readily generated from various polymers or polymer blends and posses permanent, well-defined porous structures that are independent of the solvent or reagents used. In addition such constructs offer significantly higher mass transfer compared to oval beads as they rely on convective flow instead of diffusion factors (key for reproducible optimisation and small scale synthesis). They also have a higher loading than polymers prepared by suspension polymerization due to the fact that polymerisation occurs within a single phase avoiding the problem of partitioning. It is also possible to prepare these polymer units in any shape and size which is very advantageous for the translation between micro- and meso-flow systems by readily enabling scale up in a more consistent manner.This proposal describes the preparation and use of a series of active reagent functionalized monoliths to be used in flow base synthesis.

药物发现过程正在迅速改变，以更有效，及时的方式产生更大的行为化学需求。随着全球强调达到最高的安全标准和可持续实践的发展，重新评估化学合成的进行是必要的。在药物化学中，特别是通过高通量测定和快速迭代设计的周期时间加速，这使得对过程和复合制备时间的可靠性有了新的重视。需要捕获有关正在进行的合成及其产品的信息的更加集成和连续的中继，这些信息及其产物在基本特征，物理属性及其功能方面需要被捕获。这些要求加上对柔性合成实施的渴望，似乎非常适合基于流的化学合成方法。因此，我们的结论是，未来的Medchem计划将增加对流动技术的使用，其中许多将受益于使用固体支持的试剂和清道夫。已提出并开发了用于固体支持的连续流合成合成的单层。整体是一种连续的多孔材料，可以由有机或无机材料制成。这些整体可以很容易地从各种聚合物或聚合物混合物中产生，并且具有永久的，定义明确的多孔结构，这些结构与所使用的溶剂或试剂无关。另外，与椭圆形珠相比，这种结构提供的传质依赖于对流流而不是扩散因子（可再现优化和小规模合成的关键），提供了明显更高的传质。它们的负荷也比通过悬浮聚合制备的聚合物更高，这是因为聚合发生在单个相内发生以避免分区问题。还可以以任何形状和尺寸准备这些聚合物单元，这对于微型和中间流系统之间的翻译非常有利，可以轻松以更一致的方式启用比例。该提案描述了一系列活跃的试剂官能化的官能化整体的准备，可以在流量基库中使用。