Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids

MARÍA V. DANSEY; PABLO H. DI CHENNA; ADRIANA S. VELEIRO; ZDENA KRISTOFIKOVA; HANA CHODOUNSKA; ALEXANDER KASAL; GERARDO BURTON

EUROPEAN JOURNAL OF MEDICAL CHEMISTRY

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

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

0223-5234

A procedure is described for the preparation of A-homo-5-pregnenes via an acid catalyzed rearrangement of cyclopropylcarbinols assisted by microwave irradiation. 3a-Hydroxy and 4a-hydroxy-A-homo-5-pregnen-20-one, analogues of the neuroactive steroid allopregnanolone, were obtained by means of a regioselective epoxidation of a double bond in the 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 to GABAA receptors, 3b-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 fold loss of activity