Synthesis of deuterium‐labelled chlorhexidine

Abstract

The synthesis of deuterated chlorhexidine hydrochloride is reported. The specific labelling of the saturated chain is achieved through the combination of the previously reported synthesis of 2,2,3,3,4,4,5,5-( 2 H 8 )-hexane-1,6-diol and a synthesis of carbon-14 labelled chlorhexidine. This synthesis begins with commercially available hex-2,4-yne-1,6-diol, its protection as a bis-tetrahydropyranylether, and exhaustive deuterogenation under rhodium catalysis to produce, after acid hydrolysis of the protecting groups, the saturated octadeuterated 1,6-hexanediol. Conversion of this material in two steps to the corresponding 1,6-diaminohexane was followed by the generation of guanidines with dicyanimide and final condensation with p-chloroaniline. The title compound was obtained in 10 chemical steps and in 6% overall yield.

Guanylated Diamines, Triamines, and Polyamines: Chemistry and Biological Properties

“…The synthesis of detuterium-labeled and carbon-14-labeled Chlorhexidine has been also described. The synthesis of deuterium-labeled Chlorhexidine was reported by Hudlicky and co-workers and starts from the commercially available diol 306 .…”

Synthesis of Deuterated Endochin‐Like Quinolones

“…This allows their use as internal standards for liquid chromatography-mass spectrometry (LC-MS) analysis to enable quantification of drug levels during animal and human pharmacokinetic studies. Deuterium-labeled compounds also differ in their nuclear spin quantum number, allowing their use in NMR and ESR spectroscopy [31,32]. Similarly, tritiated analogs are essential in transport and distribution studies.…”