Reagent-Based Scaffold Diversity for DNA-Encoded Library Design: Solid Phase Synthesis of DNA-Tagged sp<sup>3</sup>-Rich Heterocycles by SnAP Chemistry
Mateja Klika Škopić, Florian Losch, Angus E. McMillan, Niklas Willeke, Mateo Malenica, Luis Bering, Jeffrey W. Bode, Andreas Brunschweiger
Abstract
Reactions that require strictly dry conditions are challenging to translate to a DNA-encoded library format. Controlled pore glass solid support-connected DNA oligonucleotide–aldehyde conjugates could be condensed with SnAP reagents and cyclized to various sp3-rich heterocycles. The Boc-group of products provided a handle for product purification, and its facile removal under acidic conditions was tolerated by a chemically stabilized barcode. The reaction provides reagent-based scaffold diversity with functionalities for further library synthesis.
Topics & Concepts
ChemistryReagentOligonucleotideCombinatorial chemistrySolid-phase synthesisDNAOligonucleotide synthesisScaffoldAldehydeOrganic chemistryBiochemistryCatalysisDatabaseComputer sciencePeptideChemical Synthesis and AnalysisAdvanced biosensing and bioanalysis techniquesDNA and Nucleic Acid Chemistry