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.

为了访问生物学相关的化学空间的新领域，“不寻常”官能团的融合成为必不可少的，尤其是可以提供改进的物理化学特性或提供新颖的生物同体的群体。在这种情况下，硫胺是一个重要的机会，并且在肿瘤学中最著名的毒品候选者中越来越多地得到验证。当前，没有用于构建亚硫胺的模块化方法，也没有用于完整官能团的后期引入。该项目将通过交叉偶联方法（即形成硫胺的硫酸硫胺构建块）开发用于直接引入硫胺基团的试剂，以形成硫酸硫酸糖C-C-S-C-S-C-S C-S键。合适的设计试剂（在硫磺时有亲核的试剂）将依靠我们最近开发的N转移方法制备（例如Angew。Chem。Int。Int。2016，55，7203; Chem Commun。2017，53，348）。随后将开发与各种电力的交叉偶联反应，包括与芳基卤化物的过渡金属催化耦合。试剂将通过N功能和金属阴离子的变化来微调，以确保所需的反应性。这项工作提出了一种新型的硫酸合成方法。