Synthesis and GABAA Receptor Activity of A-Homo Analogues of Neuroactive Steroids

DANSEY, M.V.; DI CHENNA PABLO H.; VELEIRO, ADRIANA S.; KRITOFÍKOVÁ Z.; CHODOUNSKA, H.; KASAL, A.; BURTON, GERARDO

EUROPEAN JOURNAL OF MEDICAL CHEMISTRY

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Lugar: Amsterdam; Año: 2010 vol. 45 p. 3063 - 3069

0223-5234

Abstract - A procedure is described for the preparation of A-homo-5-pregnenes via an acid catalyzed rearrangement of cyclopropylcarbinols assisted by microwave irradiation. 3 -Hydroxy and 4 -hydroxy-A-homo-5-pregnen-20-one, analogues of the neuroactive steroidallopregnanolone, were obtained by means of a regioselective epoxidation of a double bond inthe expanded A-ring, using a fructose-derived chiral ketone as catalyst and oxone as oxidant.Although both these compounds were marginally active in inhibiting TBPS binding toGABAA receptors, 3 -hydroxy-A-homo-5-pregnen-20-one was almost as active as allopregnanolone. Reduction of the double bond of the latter compound resulted in a ten foldloss of activity.A receptors, 3 -hydroxy-A-homo-5-pregnen-20-one was almost as active as allopregnanolone. Reduction of the double bond of the latter compound resulted in a ten foldloss of activity.A procedure is described for the preparation of A-homo-5-pregnenes via an acid catalyzed rearrangement of cyclopropylcarbinols assisted by microwave irradiation. 3 -Hydroxy and 4 -hydroxy-A-homo-5-pregnen-20-one, analogues of the neuroactive steroidallopregnanolone, were obtained by means of a regioselective epoxidation of a double bond inthe expanded A-ring, using a fructose-derived chiral ketone as catalyst and oxone as oxidant.Although both these compounds were marginally active in inhibiting TBPS binding toGABAA receptors, 3 -hydroxy-A-homo-5-pregnen-20-one was almost as active as allopregnanolone. Reduction of the double bond of the latter compound resulted in a ten foldloss of activity.A receptors, 3 -hydroxy-A-homo-5-pregnen-20-one was almost as active as allopregnanolone. Reduction of the double bond of the latter compound resulted in a ten foldloss of activity.