| Autor: |
Merrifield JL; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Pimentel EB; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Peters-Clarke TM; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Nesbitt DJ; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States., Coon JJ; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.; National Center for Quantitative Biology of Complex Systems, Madison, Wisconsin 53706, United States.; Morgridge Institute for Research, Madison, Wisconsin 53515, United States., Martell JD; Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.; Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705, United States. |
| Abstrakt: |
Aldehydes are important synthons for DNA-encoded library (DEL) construction, but the development of a DNA-compatible method for the oxidation of alcohols to aldehydes remains a significant challenge in the field of DEL chemistry. We report that a copper/TEMPO catalyst system enables the solution-phase DNA-compatible oxidation of DNA-linked primary activated alcohols to aldehydes. The semiaqueous, room-temperature reaction conditions afford oxidation of benzylic, heterobenzylic, and allylic alcohols in high yield, with DNA compatibility verified by mass spectrometry, qPCR, Sanger sequencing, and ligation assays. Subsequent transformations of the resulting aldehydes demonstrate the potential of this method for robust library diversification. |
