Synthesis of deuterium-labelled chlorhexidine

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-(H-2(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. Copyright (c) 2007 John Wiley & Sons, Ltd.