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Synthesis 2009(20): 3391-3398  
DOI: 10.1055/s-0029-1216986
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Emilie Claudel, Cécile Arbez-Gindre, Valérie Berl, Jean-Pierre Lepoittevin*
Institut de Chimie, Laboratoire de Dermatochimie, UMR 7177, CNRS et Université de Strasbourg, 4, rue Blaise Pascal, 67070 Strasbourg, France
Fax: +33(3)68851527; e-Mail: jplepoit@unistra.fr;
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Publication History

Received 15 May 2009
Publication Date:
03 September 2009 (online)

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Abstract

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.

Key words

steroids - medicinal chemistry - isotope labeled - allergen synthesis - protecting groups

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19

THF containing a certain amount of peroxide (titration with KI and thiosulfate) was prepared as follows: In a typical procedure, THF was exposed to sunlight in an open bottle until the peroxide content reached the expected value. Alternatively, THF could be first distilled from CaO before exposure to sunlight. Fresh and aged THF may be combined to give the proper peroxide content.