ISSN 1068-1620, Russian Journal of Bioorganic Chemistry, 2006, Vol. 32, No. 1, pp. 96–98. © Pleiades Publishing, Inc., 2006.
Original Russian Text © F.V. Drozdov, V.P. Timofeev, A.Yu. Misharin, 2006, published in Bioorganicheskaya Khimiya, 2006, Vol. 32, No. 1, pp. 107–109.
LETTERS
TO THE EDITOR
A Simple Synthesis of 3b-Acetoxy-20-Oxomethylpregn-5-ene
and 3b-Acetoxy-20-Hydroxymethylpregn-5-ene
, 1
F. V. Drozdov*, V. P. Timofeev**, and A. Yu. Misharin*
* Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences,
Pogodinskaya ul. 10, Moscow, 119992 Russia
** Engelhardt Institute of Molecular Biology, Russian Academy of Sciences,
ul. Vavilova 32, Moscow, 117984 Russia
Received August 2, 2005; in final form, August 15, 2005
Abstract—3β-Acetoxy-20-oxomethylpregn-5-ene and 3β-acetoxy-20-hydroxymethylpregn-5-ene were syn-
thesized from (22R,23R)-sitost-5-ene-3β,22,23-triol in 66% overall yields.
Key words: sterols, synthesis
DOI: 10.1134/S1068162006010122
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amount of TsOH to get acetylated diol (IV); 1H NMR:
0.71 (3 H, s, H18), 0.86 (3 H, d, J 6.8, 25-CH3), 0.94
(3 H, d, J 6.8, 25-CH3), 0.95 J 7.2, 24-CH2–CH3); 1.01
(3 H, s, H19), 1.02 (3 I, d, J 6.8, H21), 2.02 (3 H, s, Ac),
3.55–3.66 (2 H, m, H22 and H23), 4.59 (1 H, m, H3),
and 5.36 (1 H, m, H6). (IV) was treated with fivefold
excess of NaIO4 in a 2 : 1 : 1 (v : v : v) methanol–chlo-
roform–water mixture at 20°C for 40 h. After extraction
of the reaction mixture with chloroform, 3β-acetoxy-
20-oxomethylpregn-5-ene (V) was isolated by a chro-
matography on silica gel in a 4 : 1 (v : v : v) hexane–
ethyl acetate mixture; yield 80%; 1H NMR: 0.68 (3 H,
s, H18), 0.87 (3 H, s, H19), 1.00 (3 I, d, J 6.8, H21),
2.10 (3 H, s, As), 4.89 (1 H, m, H3), 5.34 (1 H, m, H6),
and 9.56 (1 I, d, J 2.8, H22).
3β-Acetoxy-20-oxomethylpregn-5-ene (V) and 3β-
acetoxy-20-hydroxymethylpregn-5-ene (VI) are usu-
ally obtained by the cleavage of 22,23-double bond in
stigmasterol derivatives [1–5]. They are important
starting compounds in the synthesis of many biologi-
cally active sterols and their analogues. In a previous
communication [6], we suggested a simple synthesis of
(22R,23R)-sitost-5-ene-3β,22,23-triol (I). Below we
describe a convenient synthesis of (V) and (VI) from
triol (I) by a trivial scheme.
The treatment of (I) with 2,2-dimethoxypropane in
the presence of a catalytic amount of TsOH converted
it into 22,23-isopropylidene derivative (II); yield 83%;
1ç NMR (hereinafter, δ, ppm, J, Hz, measured on a
Bruker AMX-III-400 instrument): 0.69 (3 H, s, H18),
0.94 (3 H, d, J 6.8, 25-CH3), 0.95 (3 H, d, J 6.8, 25-
CH3), 0.95 (3 H, t, J 7.2, 24-CH2–CH3), 0.99 (3 H, s,
H19), 1.02 (3 I, d, J 6.8, H21); 1.36 (6 H, s, isopropy-
lidene), 3.51 (1 H, m, H3), 3.91 (1 H, dd, J 8.7 and 3.4)
and 3.98 (1 H, dd, J 8.7 and 2.1, H22 and H23), and
5.34 (1 H, m, H6). Acetylation of (II) (Ac2O/Py, 14 h at
3β-Acetoxy-20-hydroxymethylpregn-5-ene
(VI)
was obtained from the unseparated mixture of the peri-
odate oxidation products by the reduction with NaBH4
excess in methanol and the isolation of the target prod-
uct by crystallization from acetonitrile; yield 80% from
diol (IV); mp 132–134°ë (from acetonitrile); 1H NMR:
0.69 (3 H, s, H18), 1.01 (3 H, s, H19), 1.04 (3 I, d, J 6.8,
H21), 2.03 (3 H, s, Ac), 3.36 (1 H, dd, J 10.6, 8.6, H22),
3.62 (1 H, dd, J 10.6 and 3.2, H22), 4.59 (1 H, m, H3),
and 5.36 (1 H, m, H6).
1
20°ë) led to (III); quantitative yield; mp 188°C; H
NMR: 0.69 (3 H, s, H18), 0.94 (3 H, d, J 6.8, 25-CH3),
0.95 (3 H, d, J 6.8, 25-CH3), 0.95 (3 H, t, J 7.2, 24-
CH2CH3), 1.00 (3 H, s, H19), 1.02 (3 I, d, J 6.8, H21),
1.36 (6 H, s, isopropylidene), 2.02 (3 H, s, Ac), 3.92
(1 H, dd, J 8.2 and 3.8) and 3.98 (1 H, dd, J 8.2 and 2.4,
H22 and H23), 4.59 (1 H, m, H3), 5.36 (1 H, m, H6)].
ACKNOWLEDGMENTS
Isopropylidene group was removed from (III) by
This work was supported by the Russian Foundation
for Basic Research, project no. 03-04-48700 and the
program Molecular and Cellular Biology of the Presid-
ium of Russian Academy of Sciences.
2-h reflux in 80% acetic acid containing catalytic
1
Corresponding author; phone: +7 (095) 246-3375; e-mail:
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