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Syntheses of tritium and carbon‐14 labelled N‐ (3‐dimethyl aminopropyl) ‐N‐(ethylaminocarbonyl)‐6‐(2‐propenyl)ergoline‐8β‐carboxamide (cabergoline), a potent long lasting prolactin lowering agent
Author(s) -
Mantegani Sergio,
Brambilla Enzo,
Ermoli Antonella,
Fontana Erminia,
Angiuli Patrizia,
Vicario Gian Piero
Publication year - 1991
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580290504
Subject(s) - chemistry , cabergoline , propenyl , carboxamide , stereochemistry , medicinal chemistry , prolactin , biochemistry , hormone
The syntheses of 3 H‐ and 14 C‐labelled cabergoline (FCE 21336), namely N‐(3‐dimethylaminopropyl)‐N‐(ethylamino‐carbonyl)‐6‐(2‐propenyl)ergoline‐8 β ‐carboxamide 1 and its analogues are described. Tritiated cabergoline ([ 3 H]cabergoline) 6 , namely N‐(3‐dimethylaminopropyl)‐N‐(ethylaminocarbonyl)‐6‐(2‐ [2,3‐ 3 H]‐propenyl)ergoline‐8β‐carboxamide, was obtained, by catalytic reduction with tritium gas, according to two different synthetic procedures: A ‐ a three step route, starting from 6‐(2‐propargyl)‐dihydro lysergic acid‐methyl ester 3 gave [ 3 H]cabergoline, 97% radiochemically pure, with a specific radioactivity of 11.19 GBq/mmol and in an overall radiochemical yield of 3.5%. B ‐ a one step route, starting from 1‐ethyl‐3‐(3‐dimethyl‐aminopropyl)‐3‐6′‐(2‐propargyl)ergoline‐8′β‐ carbonyflurea 5′ yielded [ 3 H]cabergoline with a radiochemical purity >97%, specific radioactivity 1.06 TBq/mmol and radiochemical yield of 23%.A modification of this last procedure also gave [ 3 H]dihydro cabergoline ([ 3 H]FCE 23411), namely N‐(3‐dimethylaminopropyl) ‐N‐(ethylaminocarbonyl)‐6‐(2‐[2,3‐ 3 H]propyl)ergoline‐8β‐carboxamide 7 , 97% radiochemically pure and with a specific radioactivity up to 4.03 TBq/mmol. The synthesis of [ 14 C]cabergoline was carried out, in a three step route, by addition of potassium[ 14 C]cyanide to 6‐(2‐propenyl)‐8β‐chloroergoline 12 to give the expected N‐(dimethylaminopropyl)‐N‐(ethylaminocarbonyl)‐6‐(2‐propenyl)‐ergoline‐8β‐ [ 14 C]carboxamide 15 ′, 97% radiochemically pure with a specific radioactivity of 2.09 GBq/mmol and an overall radiochemical yield of 16%.