title: DNA-templated functional group transformations enable sequence-programmed synthesis using small-molecule reagents.
abstract: DNA-templated organic synthesis (DTS) has previously been used primarily to direct coupling reactions between two DNA-linked reactants. In some cases, reactants are difficult or impossible to tether to DNA oligonucleotides. The development of strategies that enable non-DNA linked small-molecule reagents to participate in sequence-programmed synthesis therefore would significantly expand the capabilities of DTS. We developed efficient DNA-templated functional group transformations of template-linked azides into corresponding amines, carboxylic acids, and thiols. The application of these reactions to a single-solution mixture of four template-linked organic azides enabled each azide to be transformed sequence specifically into a sulfonamide, carbamate, urea, or thiourea using small-molecule sulfonyl chloride, chloroformate, isocyanate, or isothiocyanate reagents not tethered to DNA. Only the four desired products were observed, without formation of any of the 12 possible undesired cross-products. Our results represent a new approach to small molecule diversification in a DNA-programmed manner.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Kaori
authors.initials: K
authors.lastname: Sakurai
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Snyder
authors.forename: David R
authors.initials: DR
authors.lastname: Liu
mesh_terms: D000588:Amines / Q000138:chemical synthesis*; D001386:Azides / Q000737:chemistry*; D002219:Carbamates / Q000138:chemical synthesis; D002264:Carboxylic Acids / Q000138:chemical synthesis*; D002625:Chemistry, Organic / Q000379:methods; D004247:DNA / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D009841:Oligonucleotides / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis*; D013449:Sulfonamides / Q000138:chemical synthesis; D013890:Thiourea / Q000031:analogs & derivatives / Q000138:chemical synthesis; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis
chemical_list: D000588:Amines; D001386:Azides; D002219:Carbamates; D002264:Carboxylic Acids; D009841:Oligonucleotides; D013438:Sulfhydryl Compounds; D013449:Sulfonamides; D014508:Urea; D004247:DNA; D013890:Thiourea