Syntheses of natural and deuterated desmosines via palladium-catalyzed cross-coupling reactions

Desmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). Herein, we describe the total synthesis of natural desmosine and its deuterated derivatives. The synthesized deuterated derivatives could be used as internal standards for the development of an isotope-dilution liquid chromatography–mass spectrometry (LC–MS/MS) analytical method for the accurate determination of desmosine in clinical samples. The key features of our synthesis are stepwise chemo- and regioselective palladium-catalyzed Sonogashira and Negishi cross-coupling reactions for the efficient introduction of the amino acid side chains onto the pyridine core.

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