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Spirocycles, Carbocycles and Heterocycles: Unified Routes via Catalyst Selection

螺环、碳环和杂环：通过催化剂选择的统一路线

基本信息

批准号：
EP/N035119/1
负责人：
Richard Taylor
金额：
$ 52.74万
依托单位：
University of York
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FN035119%2F1
关键词：
Spirocycles Carbocycles Heterocycles Unified Routes

项目摘要

Rapid access to structurally diverse organic compounds is the cornerstone of lead generation in the pharmaceutical and agrochemical industries, essential to meet the burgeoning worldwide healthcare and sustenance requirements. There is a growing realisation that traditional lead identification programmes have been limited in terms of their treatment of 3D structures and there is much current research based on the investigation of molecules which cover much wider regions of chemical space. However, such synthetic approaches to generate complex 3D organic architectures are often time-consuming and labour-intensive - and separate routes are normally required to access different types of structure. In this programme, a number of simple synthetic routes will be designed to convert cheap, readily available starting materials into high energy reactive intermediates which will be selectively converted into a range of diverse structural types by careful choice of catalysts. Attention will be given to environmental factors (low catalyst loading, telescoped procedures, scale-up potential). This part of the study will uncover fundamental principles in catalysis, mechanism and reactive intermediate chemistry. The sequences will be designed to produce products which occupy 3D space that is under-represented in typical screening libraries and which possess good 'lead-like' properties; 3D shape will be evaluated computationally using a process called principal moments of inertia (PMI). Extensions to give asymmetric variants, solid-supported options, and further diversification will be explored as will validation the novel methodology in target synthesis.In collaboration with our industrial partners, some targets will be chosen with the aim of generating potential pharmaceutical and agrochemical lead compounds which will be made available for biological screening. The proposal is underpinned by significant and promising preliminary studies and we expect that the sequences will be adopted by synthetic chemists in both industrial and academic arenas. The new chemistry and technology described fits full square in the EPSRC Dial-a-Molecule grand challenge area, and in several current Priority Areas (Catalysis, Novel and Efficient Chemical Synthesis, Sustainable Chemistry and eventually New Physical Sciences for Biology and Healthcare, and Innovative Production Processes). The new science is also relevant to the areas of catalysis and training highlighted in the EPSRC Strategic Plan 2015, with great potential in the manufacturing and healthcare sectors, also highlighted in the 2015 plan. In addition, the novel chemistry should be useful to prepare new structures relevant to the 2014 EPSRC initiative in anti-microbial resistance (AMR). Of particular importance are the potential applications of the new methodology in the UK pharmaceutical and agrochemical industries.This ambitious programme will be carried out by a PDRA over a 3 year period.

快速获得结构多样的有机化合物是制药和农化行业产生铅的基石，对于满足全球迅速增长的医疗保健和营养需求至关重要。人们越来越意识到，传统的铅识别计划在处理3D结构方面一直受到限制，目前有许多研究是基于对覆盖化学空间更广泛区域的分子的研究。然而，这种合成方法来生成复杂的3D有机建筑通常是耗时和劳动密集型的-而且通常需要单独的路线来访问不同类型的结构。在这项计划中，将设计一些简单的合成路线，将廉价、容易获得的起始材料转化为高能活性中间体，通过仔细选择催化剂，这些中间体将被选择性地转化为一系列不同的结构类型。将注意环境因素(催化剂装载量低、缩放式程序、放大潜力)。这部分研究将揭示催化、机理和反应中间化学的基本原理。这些序列将被设计成生产占据3D空间的产品，这些空间在典型的筛选库中没有被充分代表，并且具有良好的类似铅的特性；3D形状将使用称为主惯性矩(PMI)的过程进行计算评估。将探索扩展以提供不对称变体、固体支持的选择和进一步的多样化，并将在目标合成中验证新的方法。将与我们的工业合作伙伴合作，选择一些目标，目的是产生潜在的药物和农用化学品先导化合物，供生物筛选使用。这项建议得到了重要和有前景的初步研究的支持，我们预计这些序列将被工业和学术领域的合成化学家采用。所描述的新化学和技术完全符合EPSRC Dial-a-分子重大挑战领域以及当前几个优先领域(催化、新颖和高效的化学合成、可持续化学以及最终用于生物和医疗保健的新物理科学，以及创新的生产工艺)。这项新科学还与EPSRC 2015年战略计划中强调的催化和培训领域相关，在制造业和医疗保健部门具有巨大潜力，也在2015年计划中强调。此外，这种新的化学应该有助于制备与2014年EPSRC抗微生物耐药性(AMR)倡议相关的新结构。特别重要的是新方法在英国制药和农化工业中的潜在应用。这一雄心勃勃的计划将由PDRA在3年内实施。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Visible-light-induced intramolecular charge transfer in the radical spirocyclisation of indole-tethered ynones.

可见光诱导的分子内电荷转移在吲哚倾斜的YNONE的根本螺旋环境中。

DOI：
10.1039/c9sc05311e
发表时间：
2019-12-13
期刊：
Chemical science
影响因子：
8.4
作者：
Ho HE;Pagano A;Rossi-Ashton JA;Donald JR;Epton RG;Churchill JC;James MJ;O'Brien P;Taylor RJK;Unsworth WP
通讯作者：
Unsworth WP

Understanding the Role of Spiroindolenines in Pictet-Spengler Reactions