Stereoselectivity in DNA-Templated Organic Synthesis and Its Origins

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Abstract
DNA-templated synthesis is a surprisingly general strategy for controlling chemical reactivity that enables synthetic products to be manipulated in ways previously available only to biological macromolecules. The chiral nature of the DNA template raises the possibility that DNA-templated synthesis can proceed stereoselectively. Here, we show that DNA-templated substitution reactions can exhibit stereoselectivity without the assistance of chiral groups other than those present in DNA. By characterizing changes in stereoselectivity as a result of systematic changes in the structure of the template−reagent complexes, we begin to reveal the origins of the observed stereoselectivity. We propose that the conformations of nucleotides adjacent to the reactants are largely responsible for stereoselectivity. Indeed, template and reagent sequences that can adopt either a left-handed Z-form DNA helix or a normal right-handed B-form DNA helix generate opposite stereoselectivities in the Z-form and B-form even though they share the same covalent structure and the same absolute stereochemistry. Our findings establish ways in which the chirality of an information carrier can be transmitted to the stereochemistry of encoded products through templated synthesis.