Christopher J. Gerry; Zhenhua Yang; Michele Stasi; Stuart L. Schreiber
Org. Lett., 2019, 21, 5, 1325-1330
https://doi.org/10.1021/acs.orglett.9b00017

Abstract

The limited scope of DNA-compatible chemistry restricts the types of chemical features that can be incorporated into DNA-encoded libraries (DELs). Here, a method to synthesize DNA-conjugated polycyclic isoxazolidines via a [3+2] nitrone–olefin cycloaddition is described. The reaction is compatible with many olefin-containing substrates and diverse N-alkylhydroxylamines. The ability to perform subsequent DNA ligation and PCR amplification was also confirmed. This methodology facilitates the synthesis of DELs containing topographically complex compounds with under-explored chemical features.