Asymmetric Transfer Hydrogenation of Imines.

许多分子有可能以两种镜像形式存在，称为“对映体”（就像你的手）。最重要的是，构成生物有机体（细胞、动物、植物和人类）的大部分分子，包括碳水化合物、蛋白质和DNA，主要以单一对映体形式存在，即作为单一镜像。这给制药、农化和精细化工行业带来了一个具有挑战性的问题。如果一种新的化学物质被制造出来，例如一种潜在的药物、农药、中间体等，那么它也可能以对映体的混合物的形式存在，这取决于它的结构。尽管这些分子在很多方面是相同的（就像你的手一样），但它们与生物系统的相互作用可能非常不同（例如，如果我们吞下它们），因为它们会被视为两种完全不同的化合物（试着先和朋友的右手握手，然后再和他们的左手握手）。然而，生物效应的差异可能是如此之大，以至于现在法律要求化学公司以每种“手性”分别制造所有新的“对映体”化合物，并测试每种对映体的安全性和活性（有时只有一种对映体作为药物起作用，有时一种对映体是危险的，而另一种是有益的）。此外，“对映体”化合物通常也有必要以单（即最有益的）手性销售。问题是，这个看似简单的任务实际上往往相当困难，因为大多数生成新化合物的最常见和最简单的途径都会形成两种“对映体”的50:50混合物。这类似于抛硬币——当每个分子都被制造出来（每次抛硬币），那么就有50:50的机会产生任何一个手性。为了得到一个“单手性”的产物，有必要使每个分子都以相同的方式转动（每次翻转正面，或每次翻转反面）。在我们沃里克大学的研究中，我们开发了一系列催化剂，通过一个单步过程产生“对映体”分子，在这个过程中，氢被选择性地添加到底物中，从而得到一个手性明显优于另一个手性的产物（即它翻转的正面多于反面，反之亦然）。除了具有活性和选择性外，该催化剂还可以在低负荷下使用，通常相对于底物的含量低于0.5%。这减少了浪费、能源消耗和副产品。在之前的工作中，我们已经将我们的催化剂应用于对映异构纯（即单手性）醇的合成，这是许多药物靶点和中间体中所代表的关键分子类别。在这个项目中，通过在一个简单的前体分子中加入氢，催化剂将被改造成能够制造出另一类关键的分子——胺。如果成功，这将为大量有价值的合成中间体、靶分子和复杂产品提供有效的途径，否则这些产品将很难制备。

Many molecules have the potential to exist in one of two mirror image forms, known as 'enantiomers' (like your hands). Most significantly, a large proportion of the molecules from which biological organisms (cells, animals, plants, us) are made, including carbohydrates, protein and DNA, exist predominantly in a single enantiomeric form, i.e. as a single mirror image.This creates a challenging problem for the pharmaceutical, agrochemical and fine chemicals industries. If a new chemical is made, e.g. a potential drug, pesticide, intermediate etc., then this may also have to potential to exist as a mixture of enantiomers as well, depending on its structure. Although these molecules will be identical in many ways (as your hands are), they are likely to interact very differently with a biological system (i.e. if we swallow them), because they will be seen as two totally different compounds (try shaking hands with a friend's right hand and then with their left hand). The difference in biological effects, however, can be so great that now it is a legal requirement for chemical companies to make all new 'enantiomeric' compounds separately in each 'handedness' and to test each of these for safety and activity (sometimes only one enantiomer works as a drug, sometimes one is dangerous and one is beneficial). Furthermore, it is also often necessary for 'enantiomeric' compounds to be marketed in the single (i.e. most beneficial) handedness.The problem is that this (seemingly easy) task is in fact often quite difficult, because most of the most common and simple routes to new compounds form a 50:50 mixture of both 'enantiomers'. This is analogous to flipping a coin - as each molecule is made (each flip of the coin) then there is a 50:50 chance of making either handedness. To get a product of one 'handedness' it is necessary to make every single molecule the same way round (flip a head every time, or a tail every time). In our research at Warwick, we have developed a series of catalysts which generate 'enantiomeric' molecules through a single step process in which hydrogen is selectively added to a substrate to give a product in which one handedness significantly predominates over the other (i.e. it flips more heads than tails, or vice versa). As well as being active, and selective, the catalyst can be used at low loadings, typically below 0.5 % relative to substrate. This reduces waste, energy use and side products.In previous work, we have applied our catalysts to the synthesis of enantiomerically-pure (i.e. one handedness of) alcohols, which are a pivotal class of molecules represented in many pharmaceutical targets and intermediates. In this project, the catalysts will be adapted to be able to make a further pivotal class of molecules, amines, by adding hydrogen to a simple precursor molecule. If successful, this will provide an effective route to large numbers of valuable synthetic intermediates, target molecules, and complex products which would otherwise be very difficult to prepare.