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Spiroclip Technology: from Catalogue to Spirocycle in One Step

Spiroclip 技术：一步从目录到 Spirocycle

基本信息

批准号：
EP/R013748/1
负责人：
William Unsworth
金额：
$ 46.82万
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：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FR013748%2F1
关键词：
Spiroclip Technology Catalogue Spirocycle Step

项目摘要

In order to meet burgeoning worldwide healthcare and food-security demands, rapid access to diverse organic structures is the key to continued progress in the pharmaceutical and agrochemical industries. There is a growing acknowledgment that traditional synthetic approaches have been limited in terms of the range of complex 3D-structures and there is much current research based on the investigation of more 3D molecules to address this shortfall. However, such synthetic approaches to non-planar organic architectures are often time-consuming and labour-intensive.The problems of poor synthetic accessibility are particularly acute for the synthesis of a class of molecules called spirocycles, systems that have been recently identified as important but under-exploited scaffolds. The main aim of this proposal is to design and develop novel chemistry to make a diverse range of spirocyclic structural types via one-step or one-pot procedures, from catalogue starting materials, using robust and scalable protocols which will be readily adopted by industrial partners to generate building blocks, biological probes and, particularly, fragments for drug discovery. Extensions to give 'single-handed' (enantiomerically pure) variants, solid-supported options, and further diversification will be explored. Validation of the new methods in the synthesis of real drugs/biologically active materials will also be attempted. Collaborators will be consulted to ensure that the molecules made are appropriate for real-life industrial applications; e.g. they possess good 'drug-like' properties, with capacity for further elaboration, and where possible, that they occupy 3D-space that is under-represented in typical drug screening libraries. 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 anticipate that the study will also lead to advances in our knowledge of fundamental principles in catalysis, mechanism and synthetic chemistry. We also 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.

为了满足全球日益增长的医疗保健和食品安全需求，快速获得多样化的有机结构是制药和农用化学品行业持续发展的关键。越来越多的人认识到，传统的合成方法在复杂的3D结构范围方面受到限制，目前有许多研究基于对更多3D分子的研究来解决这一不足。然而，这种合成方法的非平面的有机architectures往往是耗时和劳动密集型的问题差的合成可及性是特别尖锐的一类分子称为螺环，系统最近已被确定为重要的，但开发不足的支架。该提案的主要目的是设计和开发新的化学方法，通过一步或一锅程序，从目录起始材料，使用强大和可扩展的协议，这些协议将很容易被工业合作伙伴采用，以生成构建模块，生物探针，特别是药物发现的片段。扩展到“单手”（对映体纯）的变体，固体支持的选项，并进一步多样化将进行探讨。还将尝试验证真实的药物/生物活性材料合成中的新方法。将咨询合作者，以确保所制造的分子适用于现实生活中的工业应用;例如，它们具有良好的“药物样”特性，具有进一步加工的能力，并且在可能的情况下，它们占据典型药物筛选库中代表性不足的3D空间。将可用于生物筛选的潜在药物和农业化学先导化合物。该提案得到了重要和有希望的初步研究的支持，我们预计该研究还将导致我们对催化，机制和合成化学基本原理的知识的进步。我们还期望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-Molecule重大挑战领域，以及当前的几个优先领域（催化，新颖高效的化学合成，可持续化学以及最终的生物学和医疗保健新物理科学，以及创新生产工艺）。新科学也与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领域具有巨大潜力，也在2015年计划中得到强调。此外，这种新的化学方法应该有助于制备与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业化学工业中的潜在应用。这个雄心勃勃的计划将由PDRA在3年内实施。