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Synthesis of 19-trideuterated ent-testosterone and the GABAA receptor potentiators ent-androsterone and ent-etiocholanolone

✍ Scribed by Shirisha Komarapuri; Kathiresan Krishnan; Douglas F. Covey


Publisher
John Wiley and Sons
Year
2008
Tongue
French
Weight
137 KB
Volume
51
Category
Article
ISSN
0022-2135

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✦ Synopsis


Abstract

19‐Trideuteromethyl enantiomers of androgens namely ent‐testosterone, ent‐androsterone and ent‐etiocholanolone were prepared by total synthesis. The isotope labeling at the C‐19 angular methyl group was achieved by using deuterated methyl iodide (99.5% d~3~) for introduction of C‐19 before closure of the steroid A‐ring. This method yields 19,19,19‐trideuterated steroids without increasing the number of steps involved in the total synthesis of ent‐androgens. Analysis by mass spectrometry (MS) showed no loss of deuterium during incorporation of C‐19 into ent‐testosterone. The availability of the compounds will enable these ent‐androgens to be distinguished by MS from their natural enantiomers in future pharmacokinetic and metabolic studies. Copyright © 2008 John Wiley & Sons, Ltd.