Organic Catalysts Incorporating Catalytic Triads

包含催化三元组的有机催化剂

基本信息

批准号：
EP/E052789/1
负责人：
Tom Sheppard
金额：
$ 72.31万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2007
资助国家：
英国
起止时间：
2007 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FE052789%2F1
关键词：
Organic Catalysts Incorporating Catalytic Triads

项目摘要

New chemical compounds which exhibit potentially useful biological activity / be it toxicity against cancer cells or antibiotic properties, are identified on an almost daily basis in both natural organisms and collections of man-made compounds. Subsequently, closely related structures are often examined to determine which parts of these molecules are responsible for the beneficial effects. In the course of this drug development process, thousands of molecules may be synthesized in pursuit of just one that has the desirable medical effects, is readily absorbed by the body and is non-toxic. Synthetic chemistry is therefore of fundamental importance at every stage. Meanwhile, the many recent advances in the biological sciences (such as the completion of the human genome sequence) have increased the rate at which potential targets for new disease treatments can be identified. As a consequence, the demand for drug molecules directed towards these new targets is increasing rapidly, and efficient, effective methods of chemical synthesis, particularly those which result in the construction of structural features common in drugs, are of paramount importance.The proposed research focuses on the development of new 'catalytic' methods for chemical synthesis, in which only a small quantity of chemical reagent (a 'catalyst') is required in order to convert much larger quantities of starting materials into products. The catalyst design will be inspired by natural enzymes, which are able to carry out countless chemical reactions in a catalytic fashion. We will also take inspiration from existing chemical methods for carrying out the reactions under investigation, adapting them for use in a catalytic manner. The chemical reactions which we will concentrate on have been identified in a number of recent documents (published by representatives of the global pharmaceutical industry, the American Chemical Society and the UK government research councils) as being of fundamental importance in the synthesis of drug molecules. These documents noted that there is currently a lack of efficient and environmentally-friendly chemical methods for carrying out these processes and that academic research directed towards developing such methods is urgently required.For example, amide bonds are found in more than 25% of existing drug molecules, as well as in naturally occurring molecules such as proteins, and their formation is amongst the most common of all transformations in organic chemistry. There are, however, currently no effective catalytic methods for forming these bonds. Indeed, the existing, non-catalytic technologies often require large quantities of chemical reagents that are expensive and/or toxic. We will aim to develop simple organic (carbon-based) molecules as catalysts for this reaction which will act by 'holding onto' and 'organising' the starting materials, and directing them to react together to form the amide bond. The only chemical by-products of this new process will be water and the small quantity of the catalyst itself, which can be recovered and recycled. Such a catalyst would have immediate and far-reaching application in many avenues of scientific research. The concepts outlined in this work will also be applied to the development of catalysts for many other important chemical reactions.These new catalysts will have widespread application in the synthesis of molecules for use as new drugs and agrochemicals and in the study of living cell processes, and as such will be beneficial to scientists working in many areas of chemistry, medicine and biology.

几乎每天都会在天然生物体和人造化合物中发现具有潜在有用的生物活性（无论是对癌细胞的毒性还是抗生素特性）的新化合物。随后，经常检查密切相关的结构，以确定这些分子的哪些部分产生有益效果。在这种药物开发过程中，可能会合成数千种分子，以追求一种具有理想的医疗效果、易于被人体吸收且无毒的分子。因此，合成化学在每个阶段都至关重要。与此同时，生物科学的许多最新进展（例如人类基因组序列的完成）提高了新疾病治疗潜在靶标的识别速度。因此，对针对这些新靶点的药物分子的需求正在迅速增加，高效、有效的化学合成方法，特别是那些能够构建药物常见结构特征的方法，至关重要。拟议的研究重点开发新的化学合成“催化”方法，其中只需要少量化学试剂（“催化剂”）即可将大量起始材料转化为产品。催化剂设计的灵感来自天然酶，天然酶能够以催化方式进行无数化学反应。我们还将从现有的化学方法中汲取灵感，进行所研究的反应，使其以催化方式使用。我们将重点关注的化学反应已在最近的许多文件（由全球制药行业、美国化学会和英国政府研究委员会的代表发表）中被确定为在药物分子的合成中具有根本重要性。这些文件指出，目前缺乏有效且环境友好的化学方法来进行这些过程，并且迫切需要针对开发此类方法的学术研究。例如，超过25%的现有药物中发现了酰胺键分子以及天然存在的分子（例如蛋白质），它们的形成是有机化学中最常见的转化之一。然而，目前尚无有效的催化方法来形成这些键。事实上，现有的非催化技术通常需要大量昂贵和/或有毒的化学试剂。我们的目标是开发简单的有机（碳基）分子作为该反应的催化剂，其通过“保留”和“组织”起始材料并引导它们一起反应形成酰胺键来发挥作用。这种新工艺的唯一化学副产品是水和少量的催化剂本身，可以回收和再循环。这种催化剂将在科学研究的许多领域产生直接而深远的应用。这项工作中概述的概念也将应用于许多其他重要化学反应的催化剂的开发。这些新催化剂将广泛应用于用作新药和农用化学品的分子合成以及活细胞过程的研究，因此，这将对化学、医学和生物学许多领域的科学家有益。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A rapid route to aminocyclopropanes via carbamatoorganozinc carbenoids.

DOI：
10.1002/anie.201304720
发表时间：
2013-09-16
期刊：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
影响因子：
16.6
作者：
Ishikawa, Shingo;Sheppard, Tom D.;D'Oyley, Jarryl M.;Kamimura, Akio;Motherwell, William B.
通讯作者：
Motherwell, William B.

Mechanistic insights into boron-catalysed direct amidation reactions.

DOI：
10.1039/c7sc03595k
发表时间：
2018-01-28
期刊：
Chemical science
影响因子：
8.4
作者：
Arkhipenko S;Sabatini MT;Batsanov AS;Karaluka V;Sheppard TD;Rzepa HS;Whiting A
通讯作者：
Whiting A

Halohydration of alkynols: Au-catalyzed and non-catalyzed routes to a,a-dihalo-ß-hydroxyketones

炔醇的卤水化：Au 催化和非催化途径生成 a,a-二卤-α-羟基酮