A cross-coupling approach for sulfoximine synthesis: new reagents for medicinal chemistry

亚砜亚胺合成的交叉偶联方法：药物化学新试剂

• 批准号: 1955049
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1955049
• 关键词: cross; coupling; approach; sulfoximine; synthesis

To access new areas of biologically relevant chemical space, the incorporation of "unusual" functional groups becomes essential, particularly groups that can offer improved physicochemical properties, or provide novel bioisosteres. Sulfoximines present an important opportunity in this context and are becoming increasingly validated in drug candidates, most notable in oncology. Currently there are no modular methods for the construction of sulfoximines, nor for the late stage introduction of the intact functional group.This project will develop reagents for the direct introduction of the sulfoximine group through cross-coupling methods i.e. a sulfoximine 'building block' for the formation of the sulfoximine C-S bond. Suitable designed reagents, nucleophilic at sulfur, will be prepared relying on our recently developed N-transfer methods (eg Angew. Chem. Int. Ed. 2016, 55, 7203; Chem. Commun. 2017, 53, 348). Subsequently cross-coupling reactions with various electrophiles will be developed, including transition metal catalysed couplings with aryl halides. Reagents will be fine-tuned through variation of N-functionality and metal anion to ensure desired reactivity. This work presents a novel approach to the synthesis of sulfoximines.

为了进入生物相关化学空间的新领域，掺入“不寻常”的官能团变得至关重要，特别是可以提供改进的物理化学性质或提供新颖的生物等排体的基团。亚磺酰亚胺在这方面提供了一个重要的机会，并且在候选药物中得到越来越多的验证，尤其是在肿瘤学领域。目前还没有用于构建亚砜亚胺的模块化方法，也没有用于后期引入完整官能团的模块化方法。该项目将开发通过交叉偶联方法直接引入亚砜亚胺基团的试剂，即亚砜亚胺的“构件”亚砜亚胺C-S键的形成。合适设计的硫亲核试剂将依靠我们最近开发的N-转移方法来制备（例如Angew. Chem. Int. Ed. 2016, 55, 7203；Chem. Commun. 2017, 53, 348）。随后将开发与各种亲电子试剂的交叉偶联反应，包括过渡金属催化的与芳基卤化物的偶联。试剂将通过 N-官能团和金属阴离子的变化进行微调，以确保所需的反应性。这项工作提出了一种合成亚砜亚胺的新方法。