title: Synthesis of new C-25 and C-26 steroidal acids as potential ligands of the nuclear receptors DAF-12, LXR and GR.
abstract: 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-CH3by 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.
authors.affiliation: Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (UMYMFOR), Buenos Aires, Argentina.
authors.forename: María V
authors.initials: MV
authors.lastname: Dansey
authors.affiliation: Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Pabellón 2, Ciudad Universitaria, C1428EG Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (UMYMFOR), Buenos Aires, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Del Fueyo
authors.affiliation: Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Pabellón 2, Ciudad Universitaria, C1428EG Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (UMYMFOR), Buenos Aires, Argentina. Electronic address: adrianav@qo.fcen.uba.ar.
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Veleiro
authors.affiliation: Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Pabellón 2, Ciudad Universitaria, C1428EG Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (UMYMFOR), Buenos Aires, Argentina. Electronic address: dichenna@qo.fcen.uba.ar.
authors.forename: Pablo H
authors.initials: PH
authors.lastname: Di Chenna
mesh_terms: D002782:Cholestenes / Q000138:chemical synthesis / Q000737:chemistry; D006868:Hydrolysis; D000071518:Liver X Receptors / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D002782:Cholestenes; D000071518:Liver X Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D013256:Steroids; C533800:dafachronic acid
keywords: Dafachronic acids; Glucocorticoids; Mukaiyama reaction; Oxysterols; Steroidal acids