Fluorescent labeling of alkyl chains of phosphocholine lipids by one-pot TMS cleavage-click reaction

A simple click strategy for fluorescent tagging of azide-containing alkyl-chains of phosphocholine lipids is described, based on the easily prepared TMS-alkyne-BODIPY labeling reagent (1). Lipid labeling is carried out by one-pot Ag(I)-catalyzed deprotection of 1 followed by in situ Cu(I)-mediated cycloaddition of the alkyne-dye to the azide-phospholipid counterpart, under mild hydroalcoholic conditions with high yields. Since the reaction is compatible with the phosphocholine headgroup it was exemplified here by the synthesis of a fluorescent analog of n-hexadecylphosphocholine, a leishmanicidal drug (miltefosine). In addition, the preparation of a novel, strongly fluorescent 2-acyl BODIPY dye (6) by the unprecedented one-pot Ag(I)-catalyzed TMS-cleavage/alkyne-hydration of 1, is reported; this compound may also be a convenient labeling reagent for amino-containing biomolecules.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We report a click strategy for fluorescent tagging of alkyl-chains of phosphocholines. ► The labeling is carried out by one-pot TMS-cleavage/Cu(I)-catalyzed cycloaddition. ► We report a novel one-pot Ag(I)-catalyzed TMS-cleavage/alkyne-hydration. ► A novel, strongly fluorescent 2-acyl BODIPY dye has been prepared.