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A DNA-Compatible [3+2] Nitrone–Olefin Cycloaddition Suitable for DEL Syntheses

preprint
submitted on 26.12.2018 and posted on 27.12.2018 by Christopher Gerry, Zhenhua Yang, Michele Stasi, Stuart Schreiber
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.

Funding

NIH R01GM038627

NIH R35GM127045

History

Email Address of Submitting Author

cgerry@g.harvard.edu

Institution

Harvard University

Country

United States

ORCID For Submitting Author

0000-0002-7602-0492

Declaration of Conflict of Interest

S.L.S. is a member of the Board of Directors of the Genomics Institute of the Novartis Research Foundation (“GNF”); a shareholder and member of the Board of Directors of Jnana Therapeutics; a shareholder of Forma Therapeutics; a share-holder of and adviser to Decibel Therapeutics; an adviser to Eisai, Inc., the Ono Pharma Foundation, and F-Prime Capital Partners; and a Novartis Faculty Scholar.

Version Notes

v1 - Original Submission

Exports