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Sustainable Biocatalytic Approaches to Pyridine and Piperidine Heterocycles

吡啶和哌啶杂环的可持续生物催化方法

基本信息

批准号：
BB/Y005589/1
负责人：
Timothy Bugg
金额：
$ 55.48万
依托单位：
University of Warwick
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2024
资助国家：
英国
起止时间：
2024 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FY005589%2F1
关键词：
Sustainable Biocatalytic Approaches Pyridine Piperidine

项目摘要

At present the chemicals and solvents used to make plastics, pharmaceuticals and agrochemicals are derived primarily from crude oil. As we seek to create a more sustainable world in the 21st century, our society needs to dramatically reduce its dependence upon crude oil, which means finding new, sustainable routes to make feedstock chemicals. Pyridines and piperidines are 6-membered heterocyclic rings that are commonly found in pharmaceutical drugs, and at present there is no sustainable route to substituted pyridines and piperidines. Prof Bugg's research group has discovered a biotransformation to pyridine-dicarboxylic acids from polymeric lignin found in plant biomass, using engineered Rhodococcus jostii RHA1. This proposal aims to expand this route to make a range of substituted pyridines that could be valuable feedstock chemicals. A further biotransformation is able to reduce substituted pyridines to make the corresponding saturated piperidines. We will therefore aim to use this biotransformation to generate substituted piperidines from the same route. We will also investigate the enzymes that are responsible for making the pyridine ring in Rhodococcus jostii RHA1. This research will be of considerable interest to process development scientists in the pharmaceutical industry, and we will collaborate with Astra Zeneca Pharmaceuticals to further develop this technology.

目前，用于制造塑料、药品和农用化学品的化学品和溶剂主要来自原油。当我们寻求在21世纪创造一个更可持续的世界时，我们的社会需要大幅减少对原油的依赖，这意味着寻找新的、可持续的路线来制造原料化学品。吡啶和哌啶是常见于药物中的6元杂环，目前还没有可持续的取代吡啶和哌啶的路线。Bugg教授的研究小组发现了一种生物转化，从植物生物质中发现的聚合木质素到吡啶二羧酸，使用工程化的Rhodococcus jostii RHA1。该提案旨在扩大这一路线，以制造一系列取代的吡啶，这些吡啶可能是有价值的原料化学品。进一步的生物转化能够还原取代的吡啶以制备相应的饱和哌啶。因此，我们的目标是利用这种生物转化从相同的途径产生取代的哌啶。我们还将研究在约氏红球菌RHA1中负责制造吡啶环的酶。这项研究将引起制药行业工艺开发科学家的极大兴趣，我们将与阿斯利康制药公司合作，进一步开发这项技术。