DNA-Based Asymmetric Catalysis Using G-Quadruplex Chiral Templates.

不对称催化的目的是从非手性底物中合成手性化合物。手性化合物有一种独特的手性；它不能叠加在镜像上，就像右手不能叠加在左手上一样。例如，许多生物分子是天然的手性氨基酸和糖，制药、农业和化工行业对手性化合物的需求一直在迅速上升。许多药物化合物、农用化学品、香料和香料的生物活性与绝对分子构型有关。特别是，在制药行业，以经济的方式以对映体纯形式制造手性药物的需求正在增长。许多精细化工公司都在用新的微计算机技术为制药行业服务，创新已经成为它们生存的手段。在许多学术和工业团体的激烈竞争和密集努力下，新的有效催化反应以爆炸性的速度被发现。尽管该领域正在迅速发展，但不对称催化领域仍然存在许多重大挑战。大多数不对称催化剂是由带有手性配体的金属络合物组成的。发现新的不对称催化剂的最大挑战是进行结合了有机、无机、有机金属和仿生化学的跨学科研究。为了制造高效的过渡金属催化剂，通常需要以下任务：设计和合成手性配体；制备合适的底物、催化剂前体和金属-配体络合物；寻找合适的作用条件。DNA的右旋双螺旋是自然界中最普遍和最优雅的手性例子之一，然而，大自然似乎没有利用这一性质，因为生物催化中的手性几乎完全是DNA编码的酶的结构域。然而，已报道的在化学计量DNA模板合成中DNA的手性转移导致化学反应中的非对映选择性和手性底物的对映选择性，这表明DNAzyme在不对称催化中的潜力。到目前为止，只有两个基于DNA的不对称催化的例子被报道，这项技术在双链DNA和其他DNA结构基序中仍然有很大的发展空间，尤其是G-四链体结构。G-四链体是通过自(或模板)组装形成的高阶DNA结构。G-四联体寡核苷酸由连接在碱基上的手性糖骨架组成，有两个非对位面：一个头部和一个尾部。考虑到这种固有的手性，以及已知小分子与G-四链结构紧密结合的事实，我们建议研究关键问题：与双链DNA一样，G-四链DNA能否作为手性支架，促进手性向金属催化反应的有效转移？这一过程如果成功，将开启不对称过渡金属催化的全新篇章。

The goal of asymmetric catalysis is to synthesize chiral compounds out of achiral substrates. A chiral compound has a unique handedness; it cannot be superimposed upon its mirror image, just as the right hand cannot be superimposed on the left. Many biological molecules are naturally chiral/amino acids and sugars, for instance/and the demand for chiral compounds in the pharmaceutical, agricultural, and chemical industries has been escalating rapidly. The biological activity of many pharmaceutical compounds, agrochemicals, flavors,and fragrances is associated with absolute molecular configuration. In particular, the demand is growing in the pharmaceutical industry to make chiral drugs economically in enantiomerically pure form. Many fine chemical companies are positioning themselves with new chirotechnology to serve the pharmaceuticalindustry, and innovation has been a means of business survival for them.Under tremendous competition and intensive effort from many academic and industrial groups, new and effective catalytic reactions have been discovered atan explosive rate. While the field is progressing rapidly, many significant challenges remain in asymmetric catalysis. Most asymmetric catalysts consist ofmetal complexes with chiral ligands. The greatest challenge in discovering new asymmetric catalysts is conducting interdisciplinary research that combines organic, inorganic, organometallic, and biomimetic chemistry. To make an efficient transition metal catalyst, the following tasks are generally required: designing and synthesizing chiral ligands; preparing suitable substrates,catalyst precursors, and metal-ligand complexes; and searching for appropriatereaction conditions.The right handed double helix of DNA is one of the most ubiquitous and elegant examples of chirality in nature, yet, nature does not appear to exploit this property, since chirality in biocatalysis is almost exclusively the domain of the enzymes encoded by DNA. However, the reported chirality transfer from DNA in stoichiometric DNA-templated synthesis, which leads to diastereoselectivity in chemical reactions and enantioselection of chiral substrates, suggests the potential of DNAzymes in asymmetric catalysis.To date, only two examples of such DNA-based asymmetric catalysis have been reported, and there remains much scope to develop this technology with both duplex DNA and other DNA structural motifs, most notably G-quadruplex structures.G-quadruplexes are higher order DNA structures formed through self (or templated) -assembly. The G-quartet oligonucleotide, comprising a chiral sugar backbone attached to the nucleobases have two diastereotopic faces: a 'head' and a 'tail'. In this way the nucleotide sugars transfer and amplify their chirality upon the supramolecular organisation of chiral G-quartets.Considering this inbuilt chirality, and the fact that small molecules are known to bind tightly to G-quadruplex structures, we propose to investigate the key question: As with duplex DNA, can G-quadruplex DNA function as a chiral scaffold and facilitate the efficient transfer of chirality to a metal catalysed reaction? Such a process, if successful, would open a whole new chapter in asymmetric transition metal catalysis.