Application of the Bischler–Napieralski–Pschorr radiosynthesis of (R)-(-)-[6a-14C]apomorphine, a non-selective D1/D2 dopamine receptor agonist

Abstract

A method has been developed for the carbon‐14 radiosynthesis of non‐narcotic morphine derivative (R)‐(‐)‐[6a‐14C]apomorphine (1) from the starting material 3,4‐dimethoxy‐2‐nitrophenyl‐N‐phenethyl[carboxyl‐14C]acetamide (5). The key to this synthesis was the application of the Bischler–Napieralski cyclodehydration to 1‐(3,4‐dimethoxy‐2‐nitrobenzyl)dihydro[1‐14C]isoquinoline (4), followed by N‐methylation and reduction to 1‐(3,4‐dimethoxy‐2‐nitrobenzyl)‐2‐methyl‐1,2,3,4‐tetrahydro[1‐14C]isoquinoline (3). A final Pschorr reductive ring closure followed by chiral separation to give (R)‐(‐)‐[6a‐14C]apomorphine dimethyl ether (2) and O‐demethylation led to (R)‐(‐)‐[6a‐14C]apomorphine (1) with a specific activity of 55 mCi/mmol, radiochemical purity of >98% and chiral purity of >99%. Copyright © 2006 John Wiley & Sons, Ltd.

Recent developments of enantioseparation techniques for adrenergic drugs using liquid chromatography and capillary electrophoresis: A review

“…Many adrenergic blocker enantiomers such as atenolol, alprenolol, acebutolol, metoprolol, bisoprolol and tolamolol were separated using the Chiralcel OD column [48,49]. The interactions are assumed to be the hydrogen bonding and -interaction between CSP and drugs.…”

Preparation of Enantiomerically Pure Compounds Labeled with Isotopes of Hydrogen and Carbon

“…Illustrative examples (among the many available) include the resolution of racemic [2,[3][4][5][6][7][8][9][10][11][12][13][14] C]MaxiPostÔ (1) on Chiracel OD (20 mm  250 mm, 10 mm; 9 : 1 hexane/isopropanol) 2 , the racemic 2-hydroxy [1,[2][3][4][5][6][7][8][9][10][11][12][13][14] C]arylacetic acid derivative 2 on Chiralpak AD (10 mm  250 mm, 10 mm; 4 : 1 hexane/ isopropanol) 3 , racemic [6a-14 C]apomorphine dimethyl ether (3) on Chiracel OD (4.6 mm 250 mm, 10 mm; 950 : 50 : 5 hexane/isopropanol/dimethylamine) 4 and methyl (R,S)-11tosyloxy [11-3 H]stearate (4) on Chiralpak AD (4.6 mm  250 mm, 10 mm; 100:1 heptane/ ethanol; 6 mg scale) 5 to give the enantiomers in yields of 36-47% (i.e. (enantiomerically pure) labeled compounds.…”

“…Sharpless epoxidation of racemic allylic alcohols with t-BuOOH in the presence of (2R,3R)-or (2S,3S)-diisopropyl tartrate and Ti(Oi-Pr) 4 ) have not been exploited so far for the isolation of e.p. hydroboration of racemic alkenes with diisopinocampheylborane) or an achiral reagent in the presence of an appropriate chiral catalyst (e.g.…”