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...
Saved in:
Published in | Steroids Vol. 66; no. 11; pp. 833 - 843 |
---|---|
Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
NEW YORK
Elsevier Inc
01.11.2001
Elsevier Elsevier Science |
Subjects | |
Online Access | Get full text |
ISSN | 0039-128X 1878-5867 |
DOI | 10.1016/S0039-128X(01)00113-1 |
Cover
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 |