Practical (~(14)C)-synthesis of molecules containing an acetic acid moiety: application to (~(14)C)-labeled DP1 antagonists

摘要

Efficient carbon-14 labeling of four potent and selective DP1 antagonists is reported. The synthetic sequence began with alpha-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 [~(14)C]-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).