The 14C radiolabelled synthesis of the cholesterol absorption inhibitor CP-148,623. A novel method for the incorporation of a 14C label in enones

Article abstract of DOI:10.1016/S0040-4020(97)00361-X

Isotopically labelled compounds play important roles in pharmaceutical research. New strategies for the synthesis of these compounds, carbon isotopes in particular, are needed due to the limited availability of labelled reagents. We have developed a novel method for the ¹⁴C labelling of enones and have applied it to the synthesis of a ¹⁴C radiolabelled version of the cholesterol absorption inhibitor CP-148,623. The key steps involve the 1,2 addition of [¹⁴C]methyl Grignard to a cyclic enone followed by the 'anomalous' ozonolysis of the resulting allylic alcohol utilizing a non-traditional basic work-up. In this two step procedure, the original enone was regenerated with a ¹⁴C carbon atom at the alpha position. After several standard chemical steps, the synthesis of [¹⁴C]CP-148,623 was completed. The method has also been applied to a series of other enones demonstrating the generality of the procedure for the introduction of carbon isotopes in enone systems.