Neurosteroid analogues. Part 13: Synthetic methods for the preparation of 2β-hydroxygonane derivatives as structural mimics of ent-3α-hydroxysteroid modulators of GABAA receptors

Cunde Wang, Nigam P. Rath, Douglas F. Covey

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9 Scopus citations

Abstract

Many different 3α-hydroxysteroids in the androstane and pregnane steroid series enhance the actions of γ-aminobutyric acid (GABA) at GABA type-A (GABAA) receptors in the mammalian central nervous system. Recent studies have shown that (3α,5α)-3-hydroxyandrostan-17-one (androsterone) is less active at these receptors than its enantiomer ent-androsterone. Further structure-activity relationship (SAR) studies are needed to explore the structural features of ent-androsterone that are important for its enhanced action at these receptors. Molecular modeling shows that 2β-hydroxysteroids are similar in three-dimensional shape to the enantiomers of 3α-hydroxysteroids. The development of synthetic methods to gain access to C17-substituted analogues of 2β-hydroxygonanes for SAR studies is demonstrated with the synthesis of (2β,5α,14β)-2-hydroxygonan-17-one.

Original languageEnglish
Pages (from-to)7977-7984
Number of pages8
JournalTetrahedron
Volume63
Issue number33
DOIs
StatePublished - Aug 13 2007

Keywords

  • 2β-Hydroxygonanes
  • Abnormal Beckmann rearrangement
  • Neurosteroids
  • Phenanthrenes

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