Configurational analysis and relative binding affinities of 16-methyl-5α-androstane derivatives

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Abstract

The four possible isomers 16β-hydroxymethyl-5α-androstane-3β,17β-diol 1, 16α-hydroxymethyl-5α-androstane-3β,17β-diol 2, 16β-hydroxymethyl-5α-androstane-3β,17α-diol 3 and 16α-hydroxymethyl-5α-androstane-3β,17α-diol 4 with proven configuration were converted into the corresponding 16β-methyl-5α-androstane-3β,17β-diol 5, 16α-methyl-5α-androstane-3β,17β-diol 6, 16β-methyl-5α-androstane-3β,17α-diol 7, 16α-methyl-5α-androstane-3β,17α-diol 8, furthermore into the 16β-methyl-17β-hydroxy-5α-androstane-3-one 13, 16α-methyl-17β-hydroxy-5α-androstan-3-one 14, 16β-methyl-17α-hydroxy-5α-androstan-3-one 15 and 16α-methyl-17α-hydroxy-5α-androstan-3-one 16. The steric structures of the resulting epimers were determined by means of 1H-, and 13C-NMR spectroscopy. In this way, comparison was possible with the C-16 epimers 5, 6 and 13, 14 prepared earlier by a different route, and the series of isomers could be completed with the steric structures of 16β-methyl-17α-hydroxy-5α-androstan-3β-ol 7 and 16α-methyl-17α-hydroxy-5α 8 and with their 3-keto derivatives 15 and 16. The relative binding affinities of the 16-methyl-5α-androstane-3β,17-diols 5, 6, 7, 8 and 17-hydroxy-16-methyl-5α-androstan-3-ones 13, 14, 15, 16 were studied. The introduction of a 16-methyl substituent into 5α-androstane molecules substantially decreases the binding affinity to the androgen receptor and 16α-methyl derivatives were always bound more weakly than the 16β-methyl isomers.

Original languageEnglish
Pages (from-to)833-843
Number of pages11
JournalSteroids
Volume66
Issue number11
DOIs
Publication statusPublished - Oct 2 2001

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Keywords

  • 16-Methyl steroids
  • Androgen receptor binding
  • Configurational analysis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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