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

药物发现过程正在迅速变化，产生了对更有效和更及时地进行化学的更大需求。随着全球对实现最高安全标准和可持续实践的重视的展开，重新评估化学合成是如何进行的变得越来越有必要。特别是在药物化学中，通过高通量分析和快速迭代设计加快了周期时间，重新强调了工艺和化合物制备时间的可靠性。需要获得关于正在进行的合成及其产品的基本表征、物理性质及其功能方面的更完整和持续的信息。这些要求加上对灵活合成实施的渴望，似乎非常适合基于流动的化学合成方法。因此，我们的结论是，未来的MedChem计划将越来越多地使用流动技术，其中许多将受益于固体支撑试剂和清除剂的使用。已提出并开发了用于固体支撑连续流动合成的整体。整体是一块连续的多孔材料，可以由有机材料或无机材料制成。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、定义良好的多孔结构，与所使用的溶剂或试剂无关。此外，与椭圆形微珠相比，这种结构提供了更高的传质能力，因为它们依赖对流，而不是扩散因子(这是可重复优化和小规模合成的关键)。它们的负载量也比悬浮聚合制备的聚合物高，这是因为聚合发生在单一相内，避免了分配问题。还可以制备任何形状和大小的这些聚合物单元，通过容易地以更一致的方式放大，这非常有利于微流动体系和介观流动体系之间的转换。

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.