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

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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.