权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Changing the Synthesis Landscape with Boron at the Helm: from Chiral Organometallics to Assembly Line Synthesis

以硼为主导改变合成格局：从手性有机金属到流水线合成

基本信息

批准号：
EP/I038071/1
负责人：
Varinder Aggarwal
金额：
$ 201.18万
依托单位：
University of Bristol
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FI038071%2F1
关键词：
Changing Synthesis Landscape Boron Helm

项目摘要

Chemistry is unique amongst the sciences in that it has the power to constantly rejuvenate itself since it has the ability to study what it also creates. Creating molecules is where the developments in chemistry begin, which ultimately leads to the advancements in society. Within this context, the synthesis of organic molecules is central to many research disciplines from medicine to materials. However, despite substantial progress, the problems and difficulties associated with chemical syntheses severely limit the rate of growth and development of these disciplines. These fields are constrained by what chemists can make easily, rather than by the imagination of the scientists. In order to meet the emerging challenges across new disciplinary boundaries in a rapidly changing scientific landscape we require a step-change in the development of more rapid and robust techniques in organic synthesis. Our proposal is to essentially 'grow' a carbon chain with specific substituents attached at specific places and with specific stereochemistry, so that so that at the end of the sequence a complex target molecule which may be a natural product, pharmaceutical or synthetic material will be produced essentially in one step. This is a hugely ambitious goal. The 'growth' phase is conducted using a chiral carbanion with a good leaving group attached (a carbenoid) which reacts with a boronic ester to give a homologated (enlarged) boronic ester. Repeating this reaction, using a different carbanion on the new boronic ester enables a second growth step to take place. The growth steps can be likened to adding lego pieces until a model has been created. Such a process has resonance with the remarkable machinery nature has evolved [polyketide synthases (PKS)] in its biosynthesis of polyketides. Indeed, by variation of the carbenoid and its stereochemistry (lego pieces) a diverse range of molecules with specific shape should be accessible thus enabling rapid structure-activity studies on complex molecules. The boronic ester intermediates are stable organometallic reagents which are easily accessible with control over their shape. We plan to embark on a novel method of activation of these intermediates so that they can be transformed into a much broader range of molecules bearing new functionality. Such novel methodology would significantly expand the landscape of readily available chiral organic molecules. The (desired) properties of a molecule are defined by its shape and functionality. Being able to control these critical features lies at the heart of chemistry and is what drives much of biological and materials chemistry. We aim to create new tools to enable us to easily synthesise a broad array of molecules with control over their shape and functionality. Our proposed synthesis program will provide an additional new tool to enable science.

化学在科学中是独一无二的，因为它有能力不断恢复活力，因为它有能力研究它所创造的东西。创造分子是化学发展的开始，最终导致社会的进步。在这种背景下，有机分子的合成是从医学到材料的许多研究学科的核心。然而，尽管取得了重大进展，与化学合成相关的问题和困难严重限制了这些学科的增长和发展速度。这些领域受到化学家容易制造的东西的限制，而不是科学家的想象力。为了在快速变化的科学环境中应对新学科边界的新挑战，我们需要在有机合成中发展更快速和强大的技术。我们的建议是基本上“生长”具有在特定位置连接的特定取代基和具有特定立体化学的碳链，使得在序列的末端，基本上在一个步骤中产生复杂的靶分子，所述靶分子可以是天然产物、药物或合成材料。这是一个雄心勃勃的目标。“生长”阶段使用具有良好离去基团的手性碳负离子（类卡宾）进行，其与硼酸酯反应以得到同系物化（扩大的）硼酸酯。重复该反应，在新的硼酸酯上使用不同的碳负离子使得第二生长步骤能够发生。增长的步骤可以比作添加乐高积木，直到一个模型已经创建。这样的过程与大自然在聚酮化合物的生物合成中进化出的显著机制[聚酮化合物脱氢酶（PKS）]有共鸣。事实上，通过类卡宾及其立体化学的变化（乐高积木），应该可以获得具有特定形状的各种分子，从而能够对复杂分子进行快速的结构-活性研究。硼酸酯中间体是稳定的有机金属试剂，其易于获得并控制其形状。我们计划着手研究一种新的方法来激活这些中间体，使它们能够转化为具有新功能的更广泛的分子。这种新的方法将显着扩大景观容易获得的手性有机分子。分子的（期望的）性质由其形状和功能定义。能够控制这些关键特征是化学的核心，也是生物化学和材料化学的驱动力。我们的目标是创造新的工具，使我们能够轻松地合成一系列广泛的分子，并控制它们的形状和功能。我们提出的综合计划将提供一个额外的新工具，使科学。