Reagent-Based Scaffold Diversity for DNA-Encoded Library Design: Solid Phase Synthesis of DNA-Tagged sp3-Rich Heterocycles by SnAP Chemistry

Org Lett. 2022 Feb 18;24(6):1383-1387. doi: 10.1021/acs.orglett.2c00228. Epub 2022 Feb 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemical synthesis*
  • DNA / chemistry
  • Gene Library
  • Heterocyclic Compounds / chemistry*
  • Molecular Structure
  • Solid-Phase Synthesis Techniques*

Substances

  • Heterocyclic Compounds
  • DNA