An Efficient Hemisynthesis of 20- and 21-[¹³C]-Labeled Cortexolone: A Model for the Study of Skin Sensitization to Corticosteroids

A method is described for the synthesis of isotopomers of cortexolone from the commercially available andros-4-ene-3,17-dione. The strategy is based on the use of K¹³CN for labeling at position 20 and of ¹³CH3MgI, generated in situ, for labeling at position 21. Because of the early introduction of the [¹³C] labeling, our efforts aimed at reproducible experimental procedures giving high yields with respect to the isotope containing precursors. During the development of this hemisynthesis, we noted that judicious choice of protective groups was essential as this could lead not only to mixtures or unstable intermediates but also influence considerably the output of reactions.