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变化，从而更需要以更有效和及时的方式进行化学。随着全球对实现最高安全标准和可持续实践的重视，有必要重新评估化学合成的进行方式。特别是在药物化学中，通过高通量分析和快速迭代设计来加速循环时间，这使得工艺和化合物制备时间的可靠性成为新的重点。需要在基本特性、物理特性及其功能方面更全面和持续地传递关于正在进行的合成及其产品的信息。这些要求加上灵活的合成实施的愿望似乎非常适合于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，其中许多将受益于使用固体支持的试剂和scavengers.Monoliths已经提出并开发用于固体支持的连续流动合成。整料是可以由有机或无机材料制成的单个连续的多孔材料片。这些整料可以容易地由各种聚合物或聚合物共混物和不依赖于所使用的溶剂或试剂的永久的、明确限定的多孔结构产生。此外，与椭圆形珠相比，此类结构提供了显着更高的传质，因为它们依赖于对流而不是扩散因素（对于可重复的优化和小规模合成至关重要）。它们还具有比通过悬浮聚合制备的聚合物更高的负载量，这是由于聚合在单一相中发生的事实，避免了分配问题。还可以制备任何形状和尺寸的这些聚合物单元，这对于通过容易地以更一致的方式扩大规模来在微流和中流系统之间转换非常有利。该提案描述了一系列活性试剂的制备和使用功能化整体块用于流动基合成。