A facile synthesis of pentadeuterated domiodol (2‐iodomethyl‐4‐hydroxymethyl‐1,3‐dioxolane) from glycerol‐1,1,2,3,3‐d₅

Abstract

SummaryThe acid catalyzed reaction of glycerol-d5 with bromoacetaldehyde dimethyl acetal affords the corresponding 2-bromomethyl-4-hydroxymethyl-1,3-dioxolane, which was treated with lithium iodide in 2-butanone to afford the pentadeuterated domiodol 1 in high isotopic purity. Key Words Domiodol, mucolytic drug, deuterium, synthesisFor ongoing projects to study the absorption, distribution, and excretion of the mucolytic drug domiodol (2-iodomethyl-4-hydroxymethyl-l,3-dioxolane, 1)' by gas chromatography-mass spectrometry, we needed a sample of the deuterated iododerivative 2. 2Glycerol-ds with 99% isotopic purity was commercially available (MSD isotopes, Gemany) and the synthesis of the deuterated iodo compound 2 had to be modelled on this starting labelled material.The method reported on the preparation of domiodol 1 heating at high temperatures a mixture of glycerol and iodine could not be used, since a mixture of about twenty iodinated compounds was formed? A more convenient synthesis of unlabelled domiodol 1 started from 1-benzyl glycerol 3, which reacted with bromoacetaldehyde dimethyl acetal to afford bromoderivative 41, in turn

Pharmacological uses and perspectives of heavy water and deuterated compounds

“…Dideuterated analogs of nordiazepam and diazepam were prepared to study isotope effects in oxidative reactions catalyzed by drug-metabolizing enzyme systems (Yang et al 1996). Deuterated amines (Tsuzuki et al 1996), nonsteroidal antiinflammatory 2-arylpropionic acids (Castell et al 1994), the mucolytic drug domiodol (Ferraboschi et al 1994), and artemisinins, anti-malarial drugs (Avery et al 1996) were synthesized to aid in the study of the metabolism and movement of these drugs. Deuterated penicillamine was prepared to aid in the nuclear magnetic resonance spectroscopy of peptide hormones and neutrotransmitters (Mosberg et al 1987).…”