Russian Journal of Bioorganic Chemistry, Vol. 28, No. 2, 2002, pp. 167–168. Translated from Bioorganicheskaya Khimiya, Vol. 28, No. 2, 2002, pp. 191–192.
Original Russian Text Copyright © 2002 by Ignatov, Misharin.
LETTERS
TO THE EDITOR
Stereospecific Reduction of Keto Group
in 3b-Triphenylmethoxy-5a-cholest-8(14)-en-15-one
1
D. V. Ignatov and A. Yu. Misharin
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences,
Pogodinskaya ul. 10, Moscow, 119832 Russia
Received August 03, 2001; in final form, August 16, 2001
Abstract—The reduction of 3β-triphenylmethoxy-5α-cholest-8(14)-en-15-one with lithium aluminum
hydride resulted in a quantitative yield of 3β-triphenylmethoxy-5α-cholest-8(14)-en-15β-ol.
Key words: oxysterols, synthesis
1
The development of synthetic methods for sterols
containing a hydroxyl or carbonyl group in position 15
is an important issue, since 15-oxygenated cholesterol
and lanosterol derivatives possess hypocholesterolemic
and antiatherogenic properties in mammals and exhibit
a wide spectrum of biological activities in cell cultures
Trityl-containing ketosterol (II) was obtained in a
70% yield by refluxing 15-ketosterol (I) with a fourfold
excess of trityl chloride in pyridine for 8 h and the sub-
sequent twofold recrystallization of the product from
1
1 : 2 acetone–EtOH; H NMR (hereinafter: δ, ppm; J,
Hz; CDCl3; Bruker WM 500): 0.633 (3 H, s, 19-CH3),
0.834 (6 H, d, J 6.6, 26-CH3 and 27-CH3), 0.911 (3 H,
s, 18-CH3), 0.949 (3 H, d, J 6.6, 21-CH3), 3.410 (1 H,
m, H3), 4.018 (1 H, m, H7), and 7.18–7.50 (15 H, m,
trityl).
2
[1].
The reduction of 15-ketosterol (I) and its 3-O-acetyl
or 3-O-benzoyl derivative with LiAlH4 results in a mix-
ture of isomeric diols (V), 3β15α- and 3β15β-dihy-
droxy-5α-cholest-8(14)-ene, in a 2 : 3 ratio [2].
Although these diols can be chromatographically sepa-
rated, it is obvious that the development of a reduction
method resulting in only one of the isomers is of inter-
est for the preparative synthesis of 15-hydroxysterols.
We found that the reduction of tritylated 15-ketosterol
(II) with LiAlH4 in diethyl ether leads exclusively to
one product, 3β-triphenylmethoxy-5α-cholest-8(14)-
en-15β-ol (III).
The reduction of (II) with excess LiAlH4 in diethyl
1
ether resulted in the quantitative yield of (III); H
NMR: 0.663 (3 H, s, 19-CH3), 0.834 and 0.839 (total
6 H, two d, J 6.6, 26-CH3 and 27-CH3), 0.895 (3 H, d,
J 6.6, 21-CH3), 0.992 (3 H, s, 18-CH3), 2.625 (1 H, m,
H7), 3.412 (1 H, m, H3), 4.572 (1 H, m, H15), and
7.180–7.550 (15 H, m, trityl).
The removal of the trityl protection from (III) was
achieved at 20°C by treatment with aqueous HCOOH
in ether for 20 min or with 0.1 N HCl in aqueous diox-
ane for 4 h. It was accompanied by the elimination of
the 15-hydroxy group and resulted in 3β-hydroxy-5α-
cholesta-8,14-diene; 1H NMR: 0.816 (3 H, s, 19-CH3),
0.868 and 0.870 (total 6 H, two d, J 6.6, 26-CH3 and
27-CH3), 0.938 (3 H, d, J 6.6, 21-CH3), 0.992 (3 H, s,
18-CH3), 2.356 (1 H, m, H7), 3.631 (1 H, m, H3), and
5.360 (1 H, br. s, H15) (cf. [3]).
21
18
26
19
14
7
9
15
27
8
3
Y
XO
H
To obtain 3β,15β-dihydroxy-5α-cholest-8(14)-ene
(V), (III) was preliminarily acetylated (Ac2O/Py, 20°C,
(I) X = H; Y = O
(II) X = Ph3C; Y = O
(III) X = Ph3C; Y = OH
(IV) X = Ph3C; Y = OAc
(V) X = H; Y = βOH
1
14 h) to give acetate (IV); H NMR: 1.992 (3 H, s,
CH3CO), 2.320 (1 H, m, H7), and 5.485 (1 H, m, H15).
Then the protective groups (first trityl and then acetyl)
were removed from (IV) by successive treatment with
90% aqueous HCOOH in ether (20 min, 20°C) and then
with 0.4 N NaOH in aqueous methanol (20 min, 20°C).
1
2
Please address correspondence to: phone: +7 (095) 246-3375, e-
mail: misharin@ibmh.msk.su.
Abbreviations: 15-ketosterol, 3β-hydroxy-5α-cholest-8(14)-en-
15-one.
1
Diol (V) resulted; yield 78% from (III); H NMR:
0.709 (3 H, s, 19-CH3), 0.855 and 0.857 (total 6 H, two
1068-1620/02/2802-0167$27.00 © 2002 MAIK “Nauka /Interperiodica”
Ignatov
