SYNTHESIS OF NEW C-25 AND C-26 STEROIDAL ACIDS AS POTENTIAL LIGANDS OF THE NUCLEAR RECEPTORS DAF-12, LXR AND GR

DANSEY, M.V.; DEL FUEYO, CELESTE; VELEIRO, ADRIANA S.; DI CHENNA PABLO H.

STEROIDS

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2017 vol. 121 p. 40 - 46

0039-128X

A new methodology to obtain C-25 and C-26 steroidal acids starting from pregnenolone is described. Construction of the side chain was achieved by applying the Mukaiyama aldol reaction with a non-hydrolytic work-up to isolate the trapped silyl enol ether with higher yields. Using this methodology we synthesized three new steroidal acids as potential ligands of DAF-12, Liver X and Glucocorticoid nuclear receptors and studied their activity in reporter gene assays. Our results show that replacement of the 21-CH3 by a 20-keto group in the side chains of the cholestane scaffold of DAF-12 or Liver X receptors ligands causes the loss of the activity.