Selective 19 F-Labeling of Functionalized Carboxylic Acids with Difluoromethyl Diazomethane (CF2 HCHN2 )

Pavel K Mykhailiuk; Igor Kishko; Vladimir Kubyshkin; Nediljko Budisa; Janine Cossy

doi:10.1002/chem.201703446

Selective ¹⁹ F-Labeling of Functionalized Carboxylic Acids with Difluoromethyl Diazomethane (CF₂ HCHN₂ )

Chemistry. 2017 Sep 27;23(54):13279-13283. doi: 10.1002/chem.201703446. Epub 2017 Aug 31.

Authors

Pavel K Mykhailiuk¹, Igor Kishko^{1

2}, Vladimir Kubyshkin³, Nediljko Budisa³, Janine Cossy⁴

Affiliations

¹ Taras Shevchenko National University of Kyiv, Chemistry Department, Volodymyrska 64, 01601, Kyiv, Ukraine.
² Enamine Ltd., Chervonotkatska 78, 02094, Kyiv, Ukraine.
³ Institute of Chemistry, Technical University of Berlin, Müller-Breslau-Str., 10, 10623, Berlin, Germany.
⁴ Laboratoire de Chimie Organique, Institute of Chemistry, Biology and Innovation (CBI), ESPCI Paris/ (UMR 8231) CNRS/PSL Research University, 10 rue Vauquelin, Paris, 75231 Cedex 05, France).

PMID: 28753245
DOI: 10.1002/chem.201703446

Abstract

The incorporation of fluorinated moieties into organic structures is a particularly powerful approach for generating compounds with useful biological applications in industry, pharmacology, and agriculture. Here, the recently developed reagent-CF₂ HCHN₂ -selectively esterifies carboxyl groups on organic molecules in the presence of other polar functional groups. The reaction is remarkably simple, proceeding at room temperature in chloroform without addition of a catalyst. The procedure allows "last-step" incorporation of a fluorinated ester moiety into organic structures, including bioorganic molecules such as peptides and proteins. The fluorinated ester can subsequently function as a ¹⁹ F-probe in biomolecules, thereby enabling molecular size determination by diffusion ¹⁹ F NMR experiments.

Keywords: 19F-labelling; CF2HCHN2; diazo; fluorine; peptides.