ABSTRACT Three novel 14 C‐labelled isotopologues of the psychoactive agents psilocin, psilocybin and 5‐methoxy‐ N , N ‐dimethyltryptamine (5‐MeO‐DMT) were synthesised, all labelled at the 2‐position of the indole. The syntheses involved incorporating the 3‐dimethylaminoethyl substituent common to all three substances onto a 4‐ or 5‐substituted indole intermediate via successive treatments with...
Ibrutinib is an oral medication for the treatment of B cell malignancies. During its clinical development, a stable isotopologue of ibrutinib was required for the assessment of the drug's absolute oral bioavailability via intravenous microdosing. The following work describes a 10‐step, gram‐scale production of carbon‐13 labeled ibrutinib from [13C6]phenol (13C6, 99%) in 31% overall yield with...
Ketamine is a well-known general anesthetic that inhibits cerebral NMDA receptors. Norketamine is a major circulating metabolite of this drug. A nasal spray formulation of esketamine, the S enantiomer of ketamine, is under development for the management of treatment-resistant depression. To assess the pharmacokinetic properties, C-14 labeled ketamine and norketamine were prepared separately...
Abstract The Batcho–Leimgruber strategy was employed to synthesize 3‐(2‐dimethylamino‐[ 2 H 4 ]‐ethyl)‐1 H ‐indol‐5‐ol (bufotenine, 5‐HO‐DMT) ( 8 ) from commercial 3‐methyl‐4‐nitro‐phenol ( 1 ), benzyl bromide and N,N –dimethylformamide–dimethylacetal. Compound 4 was synthesized from compound 3 using the Batcho–Leimgruber strategy in the presence of Raney nickel and hydrazine hydrate. Compound...
The synthesis and spectral properties of new radioiodinated indolealkylamines like 2-[131I]-iodo-N,N-dimethyltryptamine, 2-[131I]-iodo-N-methyltryptamine, 2-[131I]-iodo-5-methoxy-N,N-dimethyltryptamine, 2-[131I]-iodio-5-hydroxy-N,N-dimethyltryptamine (2-[131I]-iodo-bufotenine), and 2-[131I]-iodo-tryptamine and the known 2-[131I]-iodo-N-acetly-5-methoxy-tryptamine (2-[131I]-iodo-melatonine) are...
Abstract A new method is presented for the tritiation of aryl compounds with tritium gas which is conducted on the underivatized substrate. Combined directed ortho metallation and facile reduction of the carbonpotassium bond affords incorporation of tritium at high specific activity under mild conditions. The metallation/reduction method is demonstrated for the preparation of [ 3 H]ibogaine.
Abstract The synthesis of the deuterium labeled, endogenously occurring, indolealkylamine hallucinogens N,N‐dimethyltryptamine and 5‐methoxy‐N,N‐dimethyltryptamine via reduction of amide intermediates with lithium aluminum deuteride is described. The compounds were characterized with 1H, 2H and 13C NMR. These compounds were synthesized for use as probes for investigating the metabolism of these...
AbstractThe synthesis of 3,4‐methylenedioxymethamphetamine(MDMA), a serotonergic neurotoxin, labeled with tritium is described. Labeling was accomplished by N‐alkylation of the free base of the corresponding desmethyl compound using [3H]methyl iodide. The compound was purified by preparative HPLC. The radiochemical yield was about 60% based on [3H]methyl iodide. The radiochemical purity was...
AbstractA rapid and convenient synthesis of the psychotomimetic agent 4‐iodo‐2, 5‐dimethoxyphenylisopropylamine is described, incorporating the radioisotope 123I (T1/2 13 hr). With the amine function of 2, 5‐dimethoxyphenylisopropylamine blocked as the phthalimide, it was found that the aromatic 4‐position could be directly iodinated with iodine monochloride. The phthalic acid moiety was...