An Exploration of Helical Asymmetry - Development and Application of Helical Organocatalysts

螺旋不对称性的探索——螺旋有机催化剂的开发与应用

• 批准号: EP/E017495/1
• 负责人: David Carbery
• 金额: $ 25.93万
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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%2FE017495%2F1
• 关键词: Exploration; Helical; Asymmetry; Development; Application

Within the biochemical world, the helix is of prime importance. This corkscrew shaped three-dimensional structure is found in two biological polymer systems of vast importance: deoxyribonucleic acid (DNA) and many protein structures. DNA consists of two interwoven strands of polynucleotide groups and form what has become known as the double helix . This helical structure is vitally important for the safe keeping and replication of the genetic code for all life, making the shape of the helix uniquely important. Likewise, many proteins (which act as vital biological catalysts which enable so many of the body's chemical reactions to occur) have large sections that consist of a helical structure. As a result, we can appreciate the importance that this helical shape holds in biological chemistry (i.e. within our bodies). The helix also posses another important attribute. The helix is also known to be chiral, that is, it twists in either a right- or left-hended manner. These two handed twists can not be superimposed upon each other, in the same way human hands cannot be laid upon each other.In contrast to nature, mankind has not utilised this exciting design feature when performing synthetic chemistry; not in the body, but in the laboratory. The ability to form chiral molecules (that is right or left handed compounds) selectively is of huge importance, especially in the context of producing new medicines for society. This point is still pertinent as we are still greatly aware of the horrors that the lack of understanding of chiral molecules caused with the use Thalidomide (one handed form of thalidomide was effective for mothers suffering from morning sickness, the other handed form caused the birth defects of children). This helical concept will be married with the use of organic molecules which can act as molecular catalysts (like a very small enzyme) and form compounds in a selective fashion (one hand in preference to another). Often toxic transition metals are used for such purposes which may also be extremely expensive. Organic catalysts offer the chance of effective, clean and cheap formation of complicated compounds which would be of great benefit in forming new medicinal treatments. It is proposed to incorporate the unique properties of the helix when designing my new organic catalysts. As the helix forms either left or right handed corkscrews it is chiral: if the catalyst incorporates a helix, the catalyst will be chiral and can be used to form chiral molecules selectively, producing one handed form of the product over the other (e.g. left handed in preference to right). The special properties of helical compounds (shape, lack of symmetry and crystallinity) make them perfect targets for new organic catalysts. This proposal is exciting as the concept helical organic catalysts have never been investigated before. This research would offer the chance to investigate whether the special nature of the helix in biology translates to mankind's efforts to make molecules as efficient and selectively as nature can. Can the special feature of the helix in biology work in synthetic chemistry as practised by mankind? If successful, it is envisaged we will be able to synthesise new and complicated amino acids from very inexpensive malonic acid compounds. Such amino acids may be of use in designing new small proteins with potential use in medicine. The benefits to synthetic chemistry could be large. New methods for forming chiral compounds are always required, especially if they are effective and cheap. This may have significant benefits for the pharmaceutical industry in this country and potentially, for medicines in the future.

在生化世界中，螺旋非常重要。这种开瓶器形状的三维结构是在两个生物学聚合物系统中发现的：脱氧核糖核酸（DNA）和许多蛋白质结构。 DNA由两条链的多核苷酸基团组成，并形成被称为双螺旋的东西。这种螺旋结构对于所有生命的遗传密码的安全保留和复制至关重要，从而使螺旋形状具有独特的重要性。同样，许多蛋白质（充当至关重要的生物催化剂，使人体的许多化学反应发生）都具有由螺旋结构组成的大截面。结果，我们可以理解这种螺旋形状在生物化学中（即在我们体内）中所具有的重要性。螺旋还具有另一个重要属性。螺旋也是手性的，也就是说，它以右或左生态的方式扭曲。这两个手不能互相叠加，就像人类的手不能互相放置。不是在体内，而是在实验室中。形成手性分子（即右或左手化合物）的能力有选择地非常重要，尤其是在为社会生产新药物的背景下。这一点仍然是相关的，因为我们仍然非常意识到恐怖的恐怖是缺乏对使用沙利度胺引起的手性分子的理解（一种手的甲状腺膜胺形式对患有孕吐的母亲有效，另一种手形式导致了儿童的出生缺陷）。这种螺旋概念将与使用有机分子一起用作分子催化剂（例如非常小的酶）并以选择性的方式形成化合物（一只手优先于另一只手）。通常将有毒过渡金属用于这种目的，这可能也非常昂贵。有机催化剂为复杂化合物的有效，干净和廉价形成提供了机会，这将在形成新的药物治疗方面具有很大的好处。提议在设计新的有机催化剂时融合螺旋的独特性能。当螺旋形成左或右手的开瓶器时，它是手性的：如果催化剂结合了螺旋，则催化剂将是手性的，可用于选择性地形成手性分子，从而产生一种与另一个产品相对于另一个产品的手式形式（例如，左手右手右手右手右手右手）。螺旋化合物的特殊特性（形状，缺乏对称性和结晶度）使它们成为新的有机催化剂的理想目标。该建议令人兴奋，因为以前从未研究过螺旋有机催化剂。这项研究将为研究生物学中的螺旋螺旋的特殊性能是否转化为人类使分子效率和有选择性的努力是否转化为自然界的效率。生物学中的螺旋螺旋的特殊特征可以按人类实践的合成化学作用？如果成功的话，就会设想，我们将能够从非常廉价的丙二酸化合物中合成新的和复杂的氨基酸。这种氨基酸可能用于设计具有医学潜在用途的新小蛋白质。合成化学的好处可能很大。始终需要形成手性化合物的新方法，尤其是在有效且便宜的情况下。这可能会对该国的制药行业以及将来的药物带来重大好处。