Regioselective deuterium labeling of 1,4-disubstituted-1,2,3,6-tetrahydropyridines

Abstract

Reactions leading to the regioselective deuterium labeling of the 1,4‐disubstituted‐1,2,3,6‐tetrahydropyridine system are presented. Three synthetic approaches were explored: Base catalyzed proton‐deuteron exchange, reductive deuteration, and ring synthesis using deuterated agents. The methods were applied to various pyridinium salts, pyridones, and piperidones. The syntheses of several new labeled compounds are described and a brief review of the relevant literature is included. © 1997 John Wiley & Sons, Ltd.

Identification of isobaric product ions in electrospray ionization mass spectra of fentanyl using multistage mass spectrometry and deuterium labeling

“…Deuterium oxide, NaBD 4 , perdeuteropyridine, and all other reagents were supplied by Aldrich Chemical Company (St. Louis, MO, USA). The syntheses of 1 and deuterium‐labeled analogs of 1 were based on modified procedures developed for the synthesis of substituted 1,2,3,6‐tetrahydropyridines 11–16. A general synthetic scheme is outlined in Fig.…”

“…Substitution of NaBD 4 (229 mg, 5.46 mmol) for NaBH 4 in the synthesis of 1 provided 1‐d 2 (269 mg, 78.1%) following an adapted method of Mabic et al 16 . 1 H‐NMR (CDCl 3 ): δ (ppm) = 7.4–7.2 (m, 5H, ArH); 5.9–5.8 (m, 1H, vinylic H); 5.8–5.7 (m, 1H, vinylic H); 3.2–3.0 (m, 1H, C‐6 H); 3.0–2.9 (m, 2H, N‐CH 2 ); 2.8–2.6 (m, 3H, C‐2 H and CH 2 Ar); 2.3–2.2 (bs, 2H, C‐3 H).…”

“…Substitution of NaBD 4 (229 mg, 5.46 mmol) for NaBH 4 in the synthesis of 1 provided 1-d 2 (269 mg, 78.1%) following an adapted method of Mabic et al 16 (m, 2H, N-CH 2 ); 2.8-2.6 (m, 3H, C-2 H and CH 2 Ar); 2.3-2.2 (bs, 2H, C-3 H). ESI-MS m/z 190 ([MH þ ], 90.9% 2 H 2 ).…”

“…The syntheses of 1 and deuterium-labeled analogs of 1 were based on modified procedures developed for the synthesis of substituted 1,2,3,6-tetrahydropyridines. [11][12][13][14][15][16] A general synthetic scheme is outlined in Fig. 2 1-(2-Phenylethyl)-1,2,3,6-tetrahydropyridine (1)…”

Studies on the Monoamine Oxidase-B-Catalyzed Biotransformation of 4-Azaaryl-1-methyl-1,2,3,6-tetrahydropyridine Derivatives

“…Closer examination of the UV scans of incubation mixtures containing 26 or 27 and MAO-B revealed that the spectra corresponding to the dihydropyridinium metabolites 46 and 47 (Scheme ) shifted with time from a λ max of 360 nm toward a λ max of 325 nm, suggesting their further oxidation to the pyridinium species 34 and 36 , respectively. In the absence of pure synthetic standards, the possible formation of pyridinium products in these reactions was examined by GC−EIMS following treatment of the incubation mixtures with NaBD 4 . The detection of 26- 2,6 - d 2 confirmed the suspected formation of the benzimidazolylpyridinium species 34 .…”