Among the goals of organic synthesis are the high-yield production of target molecules with minimal unwanted by-products and the discovery of new molecules and new chemical reactions. In its simplest approach, organic synthesis is done in solution using reagents (reactants) at fairly high concentrations. Chemists rely on the reactive sites of the reagents to come in proximity to each other to form products. Catalysts, which bring the reactants close together and direct the stereochemistry of the products, have advanced organic synthesis by speeding up reactions, while producing little or no waste. See also: Catalysis; Organic synthesis; Stereochemistry
David R. Liu’s group at Harvard University has added a new twist to organic synthesis, called DNA-templated organic synthesis, by attaching reactants to specific short single strands of DNA (oligonucleotides). These matched DNA strands, or templates (1), combine (hybridize) through complementary pairing of the nucleotide bases [guanine (G) with adenine (A), thymine (T) with cytosine (C)] (2), bringing the reagents close enough to react and form a synthetic compound (3). See also: Deoxyribonucleic acid (DNA); Oligonucleotide
(1) GATCCATGTTAC–R1 + CTAGGTACAATG–R2
(2) GATCCATGTTAC–R1 CTAGGTACAATG–R2
(3) GATCCATGTTAC–R1R2 CTAGGTACAATG
Based on the principles of molecular biology, in DNA-templated synthesis the templates are analogous to the transcription of DNA into RNA templates and the formation of the synthetic molecule is analogous to the sequence-specific translation of the RNA template into proteins in cells. See also: Cell biology; Genetic code; Ribonucleic acid (RNA); Transcription
As long as the reactant concentrations are kept low (nanomolar), DNA-templated synthesis produces predominately one product (that is, little or no nontemplated reaction products), even when templates for close mismatches are present. Since its development, DNA-templated synthesis has been used for addition and substitution reactions, carbon-carbon bond-forming reactions, and multistep organic synthesis, including the production of polymers. DNA-templated synthesis is finding uses in medicinal chemistry for the discovery of biologically active compounds and in materials science for synthesizing molecules with well-defined and complex macromolecular architectures. See also: Polymer; Substitution reaction
