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

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-andros...

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Published inSteroids Vol. 66; no. 11; pp. 833 - 843
Main Authors Tapolcsányi, Pál, Wölfling, János, Tóth, István, Szécsi, Mihály, Forgó, Péter, Schneider, Gyula
Format Journal Article
LanguageEnglish
Published NEW YORK Elsevier Inc 01.11.2001
Elsevier
Elsevier Science
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ISSN0039-128X
1878-5867
DOI10.1016/S0039-128X(01)00113-1

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Summary: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.
ISSN:0039-128X
1878-5867
DOI:10.1016/S0039-128X(01)00113-1