Intramolecular Guanine C8-Amination for the Synthesis of Guanosine Cyclonucleosides

分子内鸟嘌呤 C8-氨基化用于鸟苷环核苷的合成

• 批准号: 2638422
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2638422
• 关键词: Intramolecular; Guanine; C8; Amination; Synthesis

Year 1: General skills training and lab rotationsYears 2-4: This work aims to deliver a proof of concept of an intramolecular guanine C8-amination reaction based on the established intermolecular platform to serve as a mechanistic probe as well as to gain access to previously synthetically intractable cyclonucleoside chemical space with potential biological interest. To this end, we propose two distinct and potentially complementary strategies to achieve cyclisation of the guanosine nucleoside.The most direct cyclising transformation would feature an intramolecular C8-amination reaction with a pendant amine functionality on the sugar motif. Not only would it challenge the reaction manifold geometrically (limiting accessible reaction pathways), kinetically (forging highly strained polycyclic structures), and electronically (containing the amine and nucleobase reaction partners in a single molecule), but it would set the stage for exploring this chemistry as a tool for constraining oligonucleotides around synthetic polyamine templates, in which one or more steps would be obligately intramolecular.

1年级：一般技能培训和实验室轮换2-4年级：这项工作旨在提供基于已建立的分子间平台的分子内鸟嘌呤c8胺化反应的概念证明，作为机制探针，并获得先前合成的难以处理的环核苷化学空间，具有潜在的生物学兴趣。为此，我们提出了两种截然不同且可能互补的策略来实现鸟苷核苷的环化。最直接的环化转化是分子内的c8胺化反应，在糖基序上有一个垂坠的胺功能。它不仅会在几何上（限制可接近的反应途径）、动力学上（锻造高度应变的多环结构）和电子上（在单个分子中包含胺和核碱基反应伙伴）挑战反应歧管，而且还会为探索这种化学作为限制合成多胺模板周围的寡核苷酸的工具奠定基础，其中一个或多个步骤将专门在分子内进行。