Syntheses of deuterium labelled atropine and scopolamine

Abstract

Easy preparative scale syntheses of deuterium labelled atropine and scopolamine are described. [ 2 H 3 ]-atropine and [ 2 H 3 ]-scopolamine are obtained in good yield and good isotopic purity in two steps starting from the unlabelled alkaloids.

ElectrochemicalN-demethylation of tropane alkaloids

“…1,7 Despite the importance of selective N-demethylation of tropane alkaloids, it has remained a challenging step for synthetic chemists. 8 Different approaches have been reported for N-demethylation of the tertiary amine in atropine and scopolamine using agents such as 2,2,2-trichloroethyl chloroformate, 9 α-chloroethyl chloroformate, 10 KMnO 4 10,11 and photochemistry. 12 Although these methods provide low to excellent yields (16-100%) of 5 and 8, they use toxic solvents and chemicals producing hazardous waste and by-products.…”

Studies on the oxidative N-demethylation of atropine, thebaine and oxycodone using a FeIII-TAML catalyst

“…This investigation has further documented the oxidative Ndemethylation of atropine (1) and the opioids, thebaine (5) and oxycodone (8a), using the Fe III -TAML catalyst 15 and various different reaction conditions. On the basis of reactivity studies, it can be concluded that the 15-catalysed N-demethylation of atropine (1) to noratropine (13) with H 2 O 2 follows a biomimetic oxidation pathway involving formation of the N-hydroxymethyl-noratropine (21) intermediate.…”

“…Here, we report further studies designed to delineate the reaction pathway of the 15-catalysed N-demethylation of 1 and the impact of various parameters on the reaction selectivity and conversion efficiency. The reactivity of the opiate alkaloids thebaine (5) and oxycodone (8a) with the 15/H 2 O 2 system has also been documented, demonstrating that N-demethylation also occurs with these compounds, but with a reduced level of selectivity under the same conditions optimised for the tropane alkaloids.…”

“…1b In contrast, N-alkylation of 1 installs the alkyl group in both axial and equatorial positions, 1a while for 2 the alkyl group is located in the equatorial position. 2 Amongst the opiate family, thebaine (5) serves as a synthetic precursor for the analgesic oxycodone (8a) and the intermediate oxymorphone (9a). 3 The latter compound is used to prepare the N-methylcyclobutyl-based analgesic nalbuphine (10) and the N-methylcyclopropyl-based opioid antagonists naltrexone (11) and nalmefene (12) (Fig.…”

“…A number of procedures have been developed to Ndemethylate 1 or 2 to nortropane derivatives, e.g. phosgene, 1b 2,2,2-tri-chloroethylchloroformate 4 or α-chloroethylchloroformate, 5 oxidative N-demethylation with KMnO 4 1b,5,6 or photochemical oxidative N-demethylation. 7 Although these methods can provide nortropane derivatives in mid to high yields (e.g.…”