Practical [14C]-synthesis of molecules containing an acetic acid moiety: application to [14C]-labeled DP1 antagonists

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 50; no. 1; pp. 1 - 5
• Main Authors: Berthelette, Carl, Wang, Zhaoyin
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 2007; Wiley
• Subjects: [14C]-synthesis; Biochemical Research Methods; Biochemistry & Molecular Biology; Biological and medical sciences; Chemistry; Chemistry, Analytical; Chemistry, Medicinal; Contrast media. Radiopharmaceuticals; DP1 antagonists; labeled compounds; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Science & Technology; tetrahydrocyclopenta[b]indol-3-yl acetic acid; tetrahydrocyclopenta[b]iridol-3-yl acetic acid; labeled compounds; [C-14]-synthesis; DP1 antagonists; Radiolabelling; Carbon Isotopes; Prostaglandin D1; Prostanoid receptor; Organic chlorine compounds; C]-synthesis; tetrahydrocyclopenta[b]indol-3-yl acetic acid; Organic fluorine compounds; Antagonist; [; Acetic acid; Chemical synthesis; Carbon 14; Labelled compound
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.1146

Efficient carbon‐14 labeling of four potent and selective DP1 antagonists is reported. The synthetic sequence began with α‐hydroxylation, reduction of an ester, followed by oxidative diol cleavage and aldehyde reduction. The resulting alcohol 4 was converted to a mesylate then nucleophilic substitution with [14C]‐sodium cyanide was performed to yield a nitrile, which upon basic hydrolysis provided the carbon‐14 labeled acid 1. Compound 2 was obtained from the same alcohol intermediate 4 and two diastereomeric compounds 6 and 7 were easily prepared from compound 2. Carbon‐14 synthesis of compounds 1, 2, 6 and 7 were achieved in good yields, high radiochemical purity (>99%) and with high specific activity (45 mCi/mmol). Copyright © 2006 John Wiley & Sons, Ltd. Efficient carbon‐14 labeling of four potent and selective DP1 antagonists is reported. The synthetic sequence began with α‐hydroxylation, reduction of an ester, followed by oxidative diol cleavage and aldehyde reduction. The resulting alcohol 4 was converted to a mesylate then nucleophilic substitution with [14C]‐sodium cyanide was performed to yield a nitrile, which upon basic hydrolysis provided the carbon‐14 labeled acid 1. Compound 2 was obtained from the same alcohol intermediate 4 and two diastereomeric compounds 6 and 7 were easily prepared from compound 2. Carbon‐14 synthesis of compounds 1, 2, 6 and 7 were achieved in good yields, high radiochemical purity (>99%) and with high specific activity (45 mCi/mmol). Copyright © 2006 John Wiley & Sons, Ltd.