title: Zirconium(IV)-Catalyzed Ring Opening of on-DNA Epoxides in Water.
abstract: DNA-encoded library technology (ELT) has spurred wide interest in the pharmaceutical industry as a powerful tool for hit and lead generation. In recent years a number of "DNA-compatible" chemical modifications have been published and used to synthesize vastly diverse screening libraries. Herein we report a newly developed, zirconium tetrakis(dodecyl sulfate) [Zr(DS)4] catalyzed ring-opening of on-DNA epoxides in water with amines, including anilines. Subsequent cyclization of the resulting on-DNA β-amino alcohols leads to a variety of biologically interesting, nonaromatic heterocycles. Under these conditions, a library of 137 million on-DNA β-amino alcohols and their cyclization products was assembled.
authors.affiliation: GlaxoSmithKline, Platform Technology & Science, 830 Winter Street, Waltham, MA, 02451, USA.
authors.forename: Lijun
authors.identifier: 0000-0003-4381-4891
authors.initials: L
authors.lastname: Fan
authors.affiliation: GlaxoSmithKline, Platform Technology & Science, 830 Winter Street, Waltham, MA, 02451, USA.
authors.forename: Christopher P
authors.identifier: 0000-0002-9049-4352
authors.initials: CP
authors.lastname: Davie
mesh_terms: D000588:Amines / Q000737:chemistry; D000605:Amino Alcohols / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004852:Epoxy Compounds / Q000737:chemistry; D023303:Oxazolidinones / Q000737:chemistry; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry*; D015040:Zirconium / Q000737:chemistry*
chemical_list: D000588:Amines; D000605:Amino Alcohols; D004852:Epoxy Compounds; D023303:Oxazolidinones; D014867:Water; D004247:DNA; D015040:Zirconium
keywords: DNA; aminolysis; encoded libraries; epoxides; zirconium