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

不对称催化的目的是从非手性底物合成手性化合物。手性化合物具有独特的手性;它不能叠加在其镜像上，就像右手不能叠加在左手上一样。许多生物分子是天然手性的，例如氨基酸和糖，并且在制药、农业和化学工业中对手性化合物的需求迅速增加。许多药物化合物、农用化学品、调味剂和香料的生物活性与绝对分子构型相关。特别地，在制药工业中，以对映体纯的形式经济地制备手性药物的需求正在增长。许多精细化工公司都将自己定位于新的手性技术，以服务于制药工业，创新已成为他们的商业生存手段。在巨大的竞争和许多学术和工业团体的密集努力下，新的和有效的催化反应以爆炸性的速度被发现。虽然该领域正在迅速发展，但在不对称催化中仍然存在许多重大挑战。大多数不对称催化剂是由金属配合物和手性配体组成的。发现新的不对称催化剂的最大挑战是进行跨学科的研究，结合有机，无机，有机金属和仿生化学。为了制备高效的过渡金属催化剂，通常需要进行以下工作：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;并寻找合适的反应条件。DNA的右手双螺旋是自然界中最普遍和最优雅的手性例子之一，然而，自然界似乎并没有利用这一特性，因为生物催化中的手性几乎完全是由DNA编码的酶的领域。然而，在化学计量的DNA模板合成中报道的从DNA的手性转移，这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，表明DNA酶在不对称催化中的潜力。迄今为止，仅报道了两个这样的基于DNA的不对称催化的例子，并且仍然有很大的空间来开发这种技术与双链体DNA和其他DNA结构基序，最值得注意的是G-四链体结构，G-四链体是通过自（或模板化）组装形成的更高级DNA结构。包含连接到核碱基的手性糖主链的G-四联体寡核苷酸具有两个非对映异构面："头“和”尾“。考虑到这种内在的手性，以及已知小分子与G-四链体结构紧密结合的事实，我们提出了研究的关键问题：与双链体DNA一样，G-四链体DNA是否可以作为手性支架，促进手性向金属催化反应的有效转移？这样的过程，如果成功的话，将在不对称过渡金属催化领域打开一个全新的篇章。

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.