The synthesis of carbon-14 labeled LY 253351 (YM 12617-1), an α1-adrenergic antagonist potentially useful in the treatment of benign prostatic hypertrophy
✍ Scribed by William J. Wheeler; Klaus K. Schmiegel; David C. Hunden
- Book ID
- 103920412
- Publisher
- Elsevier Science
- Year
- 1988
- Weight
- 90 KB
- Volume
- 39
- Category
- Article
- ISSN
- 0883-2889
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✦ Synopsis
8-[3-[(Methytthio)methyl]-6-propylergoline mesylate, a potent, long acting dopamine agonist, has been found to be useful in the treatment of Parkinson's disease. Initial metabolism studies were conducted using pergolide mesylate labeled in the N6-propyt group; however, substantial N-dealkylafion occurred in mice, resulting in loss of the label as 1~CO2. Studies were undertaken to provide pergolide mesylate labeled in the metabolically stable 17-position. 8]3-Mesyloxy-6propylergoline (synthesized from methyl dihydrolysergate via a nine step sequence), was reacted with in dimethylformamide, to form the intermediate 8~-nitrile (over 90% retention of configuration), which upon hydrolysis and borane reduction yielded 8~-hydroxymethyl-6-propylergoline-[17-~'~C]. Activation of 8~-hydroxymethyl-6-propylergoline-[17-Z4C] as its mesylate ester, followed by reaction with sodium methylmercaptide in dimethylformamide, and salt -14"r formation, yielded 8~-[(methylthio)methyl]-6-propylergolme-[17-C] mesylate.