Synthesis and transformations of 20-isoxazolylsteroids with modified D ring: I. Synthesis of 16α,17α-epoxyderivatives

Article abstract of DOI:10.1023/A:1012497111832

Synthesis of 16α,17α-epoxy-20-isoxazolylsteroids was carried out starting with dehydropregnenolone acetate. Transformation procedures for preparation therefrom of open-chain compounds were considered. Physico-chemical characteristics of compounds synthesized were investigated.

Full text of DOI:10.1023/A:1012497111832

Russian Journal of Organic Chemistry, Vol. 37, No. 6, 2001, pp. 787 792. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 6, 2001,
pp. 835 840.
Original Russian Text Copyright
2001 by Litvinovskaya, Drach, Khripach.
Synthesis and Transformations of 20-Isoxazolylsteroids
with Modified D Ring: I. Synthesis of 16 ,17 -Epoxyderivatives*
R. P. Litvinovskaya, S. V. Drach, and V. A. Khripach
Institute of Bioorganic Chemistry, Belorussian Academy of Sciences, Minsk, 220141 Belarus
Received March 22, 2000
Abstract Synthesis of 16 ,17 -epoxy-20-isoxazolylsteroids was carried out starting with dehydro-
pregnenolone acetate. Transformation procedures for preparation therefrom of open-chain compounds were
considered. Physico-chemical characteristics of compounds synthesized were investigated.
A selective introduction into a steroid molecule
with natural structure of an additional functional
group that would not significantly affect the main
biological characteristics (that would not hamper
binding with a presumed receptor) would have
permitted performing further modification and con-
jugation of the steroid to an appropriate protein
molecule and thus to prepare desired antigenes and
antibodies to the steroid compounds under investiga-
tion. This problem is urgent for various steroid
groups.
or cleavage into C22-aldehyde [1 3] cannot be
applied to the target problem since the method of sub-
stituents introduction into the D ring of these com-
pounds is lacking. Therefore we chose as the starting
compound dehydropregnenolone acetate (I), and the
synthetic approach was based on the isoxazole proce-
dure for building up the carbon backbone of the
brassinosteroid side chain [1, 4].
The first step in modification of the D ring in
the steroid molecule was the synthesis of 16 ,17 -
epoxide II by selective epoxidation of the con-
jugated double bond in dehydropregnenolone acetate
(I) effected by hydrogen peroxide in the alkaline
medium [5]. With the synthesized epoxide II was
carried out a reaction with Grignard reagent, acetyl-
enemagnesium bromide. We established that the
arising acetylene alcohol III contained two epimers
at C20 atom which were virtually indistinguishable
both by chromatography and 1H NMR spectra.
The formation of two epimers was detected only
with the use of 13C NMR spectroscopy (the
13C NMR spectrum contained a double set of signals
from the atoms C12, C13, C14, C16, C20 and C23
indicating the presence of two epimers at the C20
atom).
The building up of the side chain for C27-steroids
was further performed along the nitriloxide procedure
[4, 6] that we had tested before for unsubstituted
in the D ring pregnane compounds. The addition to
acetylene alcohol III of isobutyronitriloxide generated
by treating the isobutyraldoxime with N-chloro-
succinimide in the presence of triethylamine resulted
in regioselective formation of 20-hydroxy-20-iso-
xazolylsteroid (IV). The addition occurred at the
triple bond and did not affect the 5(6) bond.
Achievement of this target with regard to a new
phytohormone class, brassinosteroids, should transfer
the studies thereof to a new qualitative level. Thus
would arise possibilities to investigate the reception
of brassinosteroids, to develop highly sensitive
microanalytical reagents necessary for the study of
brasinosteroids spreading in plants, their bio-
synthesis, metabolism etc. It is presumable that the
preparation of synthetic analogs would furnish new
bioactive substances.
The target of the present study was a development
of procedures for regio and stereoselective chemical
modification of brassinosteroids and preparation of
their analogs with an additional functional moiety
attached to one of the carbon atoms (preferably
to C16 or C17).
The traditional ways of brassinosteroid synthesis
based on transformation of ergosterol or stigmasterol
22
and involving
bond for subsequent hydroxylation
*
The study was carried out under financial support of the
Foundation for Basic Research of Belorussian Republic
(grant no. [97-079).
1070-4280/01/3706-0787$25.00 2001 MAIK Nauka/Interperiodica

788
LITVINOVSKAYA et al.
The obtained 20-hydroxy-20-isoxazolylsteroid (IV)
was done by reduction on Raney nickel in ethanol.
After this procedure was effected with 20(21)-en-20-
isoxazolylsteroid (VI) were separated two products:
24-amino-20(21),23-diene-22-one (VIII) produced by
opening of the isoxazole ring, and 24-amino-23-en-
22-one (IX) originating from heterocycle opening
and hydrogenation of the 20(21)-bond. The hydro-
after protection of the hydroxy group was subjected
to treatment with thionyl chloride in tetrahydrofuran
in the presence of pyridine to perform dehydration
[7]. The use of freshly distilled thionyl chloride
provided in good yield 20(21)-steroid (VI) whose
structure was confirmed by its physico-chemical
characteristics: the lack of absorption band from
stretching vibrations of hydroxy group in the IR
genation time virtually did not affect the ratio of the
20(21)
enamines formed. Note that the separated
-
1
spectrum, and the presence in the H NMR spectrum
steroid (VIII) under the indicated conditions can be
further transformed into compound IX with the use
of catalytical amounts of Raney nickel. Probably the
complete hydrogenation of the 20(21)-bond requires
the presence of fresh catalyst. It should be noted that
the reduction of the double bond yielded a single
stereoisomer.
of two one-proton singlets from vinyl protons
attached to C21 ( 5.48 and 6.10 ppm ). At use in
the above reaction of thionyl chloride with hydrogen
chloride traces alongside dehydration product VI was
also obtaine 17 -chloroderivative VII originating
from cleavage of the epoxy ring followed by cycliza-
tion of the arising 16,20-diol into the corresponding
oxetane. The structure and composition of the
The structure of compound VIII is confirmed by
1
the presence in its H NMR spectrum of two signals
1
compound were determined from H, 13C NMR, IR,
from vinyl protons attached to atom C21 ( 5.48 and
6.12 ppm), two broadened one-proton singlets (
5.22 and 10.05 ppm) characteristic of amino group,
and a singlet from vinyl proton linked to C23 atom (
and mass spectra, and also from elemental analysis
with chlorine trapping by silver powder [8].
The transition from the isoxazoles obtained to the
steroids with an open functionalized cholesterol chain
1
5.56 ppm). A characteristic signal in the H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 6 2001

SYNTHESIS AND TRANSFORMATIONS OF 20-ISOXAZOLYLSTEROIDS: I.
789
R = H (X, XII, XIV); Ac (XI, XIII, XV).
spectrum of compound IX is the three-proton doublet
at 1.18 ppm inherent to the protons of 21-methyl
group, and no vinyl protons at C21 atom.
of 21-methyl group protons in the Z-isomer was
located in the stronger field (see Scheme).
Isoxazole X was cleaved on Raney nickel freshly
saturated with hydrogen to afford 24-amino-23-en-
22-one (XII) in 50% yield. The structure of the latter
was confirmed by 13C NMR spectrum and appearance
The reductive cleavage of 16,20-oxy-20-isoxazol-
ylsteroid (VII) on Raney nickel proceeded in several
directions affording a product mixture therefrom we
succeeded to isolate only 17-20-isoxazolylsteroid (X)
formed by cleavage of the oxetane ring and dehydro-
chlorination, and 24-amino-23-en-22-one (XII),
1
of characteristic signals in the H NMR spectrum
(three-proton singlet of the methyl group attached to
the double bond at 2.03 ppm, one-proton doublet of
the 16 -proton at 4.42 ppm, one-proton singlet of
the vinyl proton at C23 atom, 5.18 ppm, and two
broadened singlets of the protons of the amino group
at 5.24 and 10.08 ppm). In the IR spectrum of com-
pound XII is observed an absorption band of stretch-
resulting from the cleavage of both oxetane and
17
isoxazole rings followed by dehydrochlorination.
-
20-Isoxazolylsteroid (X) formed as a mixture of two
geometrical isomers Xa, b with respect to the bond
17(20)
1
as follows from the H NMR spectrum. In the
1
ing vibrations of hydroxy group (3420 cm ). The
latter appear two singlets belonging to the protons of
methyl groups attached to the double bond ( 2.12
and 2.14 ppm), and a doublet from the proton at C16
atom ( 4.82 ppm). The presence of a hydroxy group
is confirmed by the absorption band of stretching
acetylation of the secondary alcohol XII with acetic
anhydride in pyridine at room temperature results in
3,16-diacetoxy-24-acetamido derivative XIII as
revealed by 1H NMR spectrum: downfield shift of the
resonance from the proton attached to C16 ( 5.86),
three three-proton singlets belonging to acetate groups
( 1.97, 2.03, and 2.16 ppm), and only one singlet
from the amino group proton ( 12.54 ppm).
1
vibrations at 3410 cm in the IR spectrum, and also
1
by appearance in the H NMR spectrum of an addi-
tional three-proton singlet of acetate methyl after
acetylation of compound X into acetate XI. In the
1H NMR spectrum of the latter the signal of the
proton at C16 atom is sifted downfield ( 5.80 ppm).
Acetylation also removes the absorption band of the
hydroxy group stretching vibrations from the IR
spectrum. We succeded to isolate the individual iso-
mers by chromatography. The assignement of Xa to
E-isomer and Xb to Z-isomer was done basing on
1H NMR spectra and literature data [9] for the signal
Thus we developed a synthesis of 16 ,17 -epoxy-
20-isoxazolylsteroids proceeding from dehydro-
pregnenolone. The reductive cleavage of the com-
pounds obtained on Raney nickel permits transforma-
tion thereof into open-chain compounds, in particular,
into 24-amino-23-en-22-ones. The transition from the
latter to the known key intermediates leading to
brassinisteroids we already described before [10].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 6 2001

790
LITVINOVSKAYA et al.
ture was treated with saturated ammonium chloride
EXPERIMENTAL
solution, the reaction product was extracted with
ethyl acetate, the extract was dried with sodium
sulfate, and the solvent was evaporated. The residue
was charged into a column packed with the silica gel,
elution was performed with a mixture toluene ethyl
acetate (4: 1). We obtained 0.96g (92%) of the acetyl-
1H NMR spectra were registered on spectrometer
Bruker A-200 (200 MHz) in deuterochloroform,
internal reference TMS. IR spectra were recorded on
UR-20 spectrophotometer (from thin film, solution
in CCl4, or KBr pellets). Mass spectra were measured
on Hewlett-Packard 5890 instrument with the linear
temperature programming from 40 to 280 C at the
1
ene alcoholIII. mp 192 193 C (methanol). H NMR
spectrum ( , ppm): 1.03 s (3H, 18-Me), 1.05 s (3H,
19-Me), 1.63 s (3H, 21-Me), 2.55 s (1H, H23), 3.09 s
(OH), 3.47 s (1H, H16), 3.55 m (1H, H3), 5.35 m
(1H, H6). 13C NMR spectrum ( C, ppm): 16.6q,
19.3q, 20.6t, 26.9 t, 28.6 and 28.8 q, 30.0 d, 31.2 t,
31.6 t, 33.2 two t, 36.7 s, 37.2 t, 41.9 t, 42.9 two s,
47.0d, 50.5d, 59.4 and 59.6d, 66.6 and 67.5s, 71.3d,
72.5 and 73.4 s, 72.6 and 72.7 s, 86.3 and 86.8 d,
1
rate 10 deg min , ionizing electrone energy 70 eV.
UV spectra were obtained on Specord M-400 spectro-
photometer from methanol or ethanol solutions. The
melting points were determined on Koeffler heating
block.
The reactions were monitored by TLC on Silufol-
UV-254 and Kieselgel 60 F254 (Merck) plates.
Chromatographic separation was carried out on silica
gel 40/60 (Kieselgel 60, Merck).
1
121.2 d, 141.3 s. IR spectrum (KBr, cm ): 3450,
3300, 2950, 2920, 2875, 1650, 1480, 1450, 1390,
1360. Mass spectrum (m/z): 356, 323, 305, 270.
Epoxidation of 16-dehydropregnenolone acetate
(I). To a solution of 1 g (3 mmol) of dehydro-
pregnenolone acetate (I) in 10 ml of ethanol at 30
40 C was added 6 ml of 30% hydrogen peroxide and
3.6 ml of 4 N NaOH. The reaction mixture was
stirred for 2 h, then 300 ml of cold water was
added. The precipitate was filtered off, the solution
was dried with sodium sulfate. The solvent was
evaporated, the residue was crystallized from
methanol dichloromethane mixture. The yield of
epoxide II 0.84 g (91%).
3 ,20S-Dihydroxy-20-(isopropylisoxazol-5-yl)-
16 ,17 -epoxypregn-5-ene (IV). To a suspension of
0.8 g (6 mmol) of N-chlorosuccinimide in 5 ml of
chloroform was added several drops of pyridine and
then a solution of 0.45 g (6 mmol) of isobutyrald-
oxime in 2 ml of chloroform. The mixture was stirred
for 15 min, and thereto was added 0.68 g (2 mmol) of
acetylene alcohol III in 2 ml of chloroform. In
10 min was started addition of 0.85 ml (6 mmol) of
triethylamine in chloroform that was performed
dropwise and proceeded for 4 h. Then the reaction
mixture was left overnight. The reaction mixture was
washed with water, dried with sodium sulfate, the
solvent was evaporated, and the residue was subjected
to chromatography on a column packed with silica
gel, eluent toluene ethyl acetate, 1: 1. We obtained
0.77 g (91%) of isoxazole IV as oily substance.
1H NMR spectrum ( , ppm): 0.90 s (3H, 18-Me),
0.97 s (3H, 19-Me), 1.24 d (6H, CHMe2, J 7 Hz),
1.66 s (3H, 21-Me), 3.04 m (1H, CHMe2), 3.48 m
(1H, H3), 3.52 s (1H, H16), 5.30 m (1H, H6), 6.14 s
(1H, H4 ).
3 -Hydroxy-16 ,17 -epoxypregn-5-ene (II). mp
1
179 180 C (methanol). H NMR spectrum ( , ppm):
1.04 s (3H, 18-Me), 1.08 s (3H, 19-Me), 2.05 s (3H,
21-Me), 3.58 m (1H, H3), 3.70 br.s (1H, H15), 5.35
m (1H, H6). 13C NMR spectrum ( C, ppm): 15.5 q,
19.3 q, 20.4 t, 25.9 q, 27.5 t, 29.7 d, 31.3 t, 31.4 t,
31.5 t, 36.7 c, 37.0 t, 41.4 s, 42.1 t, 45.5 d, 50.3 d,
60.5 d, 71.0 s, 71.5 d, 121.0 d, 141.1 s, 205.0 s. IR
1
spectrum (cm ): 3450, 2950, 2915, 2870, 1705,
1645, 1450, 1380, 1310. Mass spectrum (m/z): 331,
312, 296, 294, 262, 253.
3 -Acetoxy-20-(isopropylisoxazol-5-yl)-16 ,17 -
epoxypregna-5,20(21)-diene (VI). To a stirred solu-
tion of 0.480 g (1 mmol) of steroid alcohol V in
20 ml of tetrahydrofurane was added 0.3 ml of
pyridine. The mixture was cooled to 50 C, and
0.33 ml (1.84 mmol) of freshly distilled thionyl
chloride in 5 ml of tetrahydrofuran was added thereto.
Within 1 h the reaction mixture was warmed to room
temperature, and then 100 ml of 5% solution of
sodium hydrogen carbonate was added to the reaction
mixture. The reaction product was exreacted into
3 ,20S-Dihydroxy-16 ,17 -epoxy-24-norchol-5-
en-22-yne (III). Into Grignard reagent prepared from
0.36 g (15 mmol) of magnesium and 1.4 ml
(16 mmol) of ethyl bromide in 40 ml of anhydrous
tetrahydrofuran 10 min after complete dissolution of
magnesium was passed acetylene for 30 min (the reac-
tion mixture self-heated to 40 C). After cooling the
reaction mixture to room temperature a solution of
0.98 g (3 mml) of epoxyketone II in 20 ml of tetra-
hydrofuran was added, and the mixture was stirred
for 2 h at room temperature. Then the reaction mix-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 6 2001

SYNTHESIS AND TRANSFORMATIONS OF 20-ISOXAZOLYLSTEROIDS: I.
791
ethyl acetate, the extract was washed with the solution
of sodium hydrogen carbonate, dried with anhydrous
sodium sulfate, and evaporated. The residue was
subjected to chromatography on a column packed
with silica gel, eluent hexane ethyl acetate, 3: 1.
We obtained 0.35 g (80%) of compound VI as oily
By this procedure from 0.15 g isoxazolylsteroid
VI was obtained 0.02 g (14%) of 20(21),23-dien-22-
one VIII and 0.015 g (10%) of enaminoketone IX.
24-Amino-3 -acetoxy-16 ,17 -epoxycholesta-
5,20(21),23-trien-22-one (VIII) was isolated as oily
1
substance. H NMR spectrum ( , ppm): 0.88 s (3H,
1
substance. H NMR spectrum ( , ppm): 0.93 s (3H,
18-Me), 1.02 s (3H, 19-Me), 1.20 d (6H, CHMe2, J
7 Hz), 2.04 s (3H, OAc), 2.40 m (1H, CHMe2),
3.52 s (1H, H16), 4.60 m (1H, H3), 5.22 br.s (1H,
NH), 5.38 m (1H, H6), 5.48 d and 6.12 d (2H, H21,
J 1.5 Hz), 5.56 s (1H, H23), 10.05 br.s (1H, NH). IR
18-Me), 1.05 s (3H, 19-Me), 1.30 d (6H, CHMe2, J
7 Hz), 2.03 s (3H, OAc), 3.07 s (1H, CHMe2), 3.54
s (1H, H16), 4.60 m (1H, H3), 5.38 m (1H, H6),
5.48 s and 6.10 s (2H, H22), 6.27 s (1H, H4 ). 13C
NMR spectrum ( C, ppm): 16.3 q, 19.9 q, 21.3 t,
22.0 q, 22.4 q, 27.1 q, 28.0 t, 28.3 t, 31.3 t, 32.2 t,
33.2 t, 37.4 s, 37.5 t, 38.7 t, 43.1 s, 46.2 d, 50.9 d,
61.6 d, 71.4 s, 74.4 d, 101.5 d, 121.3 t, 122.7 d,
130.9 s, 140.6 s, 167.9 s, 170.2 s, 171.1 s. IR
1
spectrum (film, cm ): 2980, 2960, 2870, 1745,
1625, 1540, 1470, 1455, 1370, 1255.
24-Amino-3 -acetoxy-16 ,17 -epoxycholesta-
5,23-dien-22-one (IX) was isolated as oily substance.
1H NMR spectrum ( , ppm): 0.92 s (3H, 18-Me),
1.02 s (3H, 19-Me), 1.18 d (9H, 21-Me and
CHMe2, J 7 Hz,), 2.04 s (3H, OAc), 3.52 s (1H,
H16), 4.60 m (1H, H3), 5.04 br.s (1H, NH), 5.38 m
(1H, H6), 5.58 s (1H, H23), 9.80 br.s (1H, NH).
1
spectrum (film, cm ): 2980, 2950, 2870, 1745,
1590, 1480, 1460, 1390, 1380, 1260. UV spectrum
[EtOH, $8max, nm ( )]: 250 (6500).
Along the same procedure of application of the
thionyl chloride with traces of hydrogen chloride
was obtained from 0.42 g of stroid alcohol V 0.18 g
(40%) of diene VI and 0.23 g (54%) of 17-chloro-
derivative VII.
1
IR spectrum (film, cm ): 2980, 2960, 2870, 1735,
1620, 1535, 1470, 1455, 1370, 1255.
By the above procedure from 0.195 g (0.4 mmol)
of compound VII was obtained 0.151 g (83%) of
isomer mixture of compound X and 0.012 g (6%) of
compound XII.
3 -Acetoxy-20-(3-isopropylisoxazol-5-yl)-16 ,20-
oxy-17 -chloropregna-5-ene (VII). mp 137 138 C
1
(methanol). H NMR spectrum ( , ppm): 0.55 s (3H,
(17E,Z)-3 -Acetoxy-16 -hydroxy-20-(3-isoprop-
ylisoxazol-5-yl)pregna-5,17-diene (X) was isolated
as oily substance. H NMR spectrum ( , ppm): 0.98 s
18-Me), 1.00 s (3H, 19-Me), 1.30 d (6H, CHMe2,
J 7 Hz), 1.80 s (3H, 21-Me), 2.03 s (3H, OAc), 3.04
m (1H, H25), 3.70 br.s (1H, H16), 4.60 s (1H, H3),
5.36 m (1H, H6), 6.36 s (1H, H4 ). 13C NMR
spectrum ( C, ppm): 14.4 q, 19.1 q, 20.5 t, 21.4 q,
21.6 q, 21.7 q, 26.6 q, 27.0 t, 27.7 t, 29.6 d, 29.9 d,
31.4 t, 33.6 t, 36.7 s, 36.8 t, 38.0 t, 44.6 s, 46.6 d,
50.0 d, 61.0 d, 67.3 s, 71.1 s, 73.8 d, 102.0 d,
122.1 d, 139.9 s , 169.3 s, 170.4 s, 173.6 s. IR
1
and 1.05 s (3H, 18-Me), 1.02 s (3H, 19-Me), 1.30 d
(6H, CHMe2, J 7 Hz), 2.02 s and 2.04 s (3H,
OAc), 2.12 s and 2.14 s (3H, 21-Me), 3.04 (1H,
CHMe2), 4.60 m (1H, H3), 4.82 d (1H, H16, J 5 Hz),
5.38 m (1H, H6), 5.97 s and 6.20 s (1H, H4 ). IR
1
spectrum (film cm ): 3440, 2975, 2960, 2915, 2880,
1
1745, 1680, 1590, 1470, 1460, 1425, 1380, 1245.
UV spectrum [EtOH, max, nm ( )]: 256 (13470).
spectrum (cm ): 2980, 2960, 2880, 1745, 1610,
1475, 1460, 1380, 1250. Mass spectrum (m/z): 387,
361, 324, 309, 279, 253. Found, %: C 68.88, 68.57;
H 7.93, 8.14; Cl 6.94, 6.58; N 2.79. C29H39ClNO4.
Calculated, %: C 69.39; H 7.97; Cl 7.07; N 2.68.
The isomers of compound X obtained were
separated on a column packed with silica gel, eluent
toluene ethyl acetate, 5: 1. The more polar isomer
Xa is of E-confuguration, the less polar one, Xb,
possesses Z-configuration.
Cleavage of 20-isoxazolylsteroids. Raney nickel
of W-2 grade (100 mg) was saturated with hydrogen
at stirring in 10 ml of ethanol for 2 h. Then 0.1 mmol
of 20-isoxazolylsteroid in 10 ml of ethanol was
added. The reaction mixture was stirred at room
temperature under hydrogen atmosphere for 3 h. At
the end of the reaction the catalyst was filtered off,
and the solvent was evaporated. The residue was
purified by chromatography on silica gel (eluent
toluene ethyl acetate, 3: 1).
(17E)-3 -Acetoxy-16 -hydroxy-20-(3-iso-
propylisoxazol-5-yl)pregna-5,17-diene (Xa) was
1
isolated as oily substance. H NMR spectrum ( ,
ppm): 1.05 s (3H, 18-Me), 1.02 s (3H, 19-Me), 1.30
d (6H, CHMe2, J 7 Hz), 2.04 s (3H, OAc), 2.14 s
(3H, 21-Me), 3.05 (1H, CHMe2), 4.60 m (1H, H3),
4.82 d (1H, H16), J 5 Hz), 5.38 m (1H, H6), 6.20 s
1
(1H, H4 ). IR spectrum (cm ): 3440, 2980, 2960,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 6 2001

792
LITVINOVSKAYA et al.
2915, 2880, 1745, 1680, 1590, 1470, 1460, 1425,
1380, 1240.
1.00 s and 1.04 s (3H, 18-Me), 1.02 s (3H, 19-Me),
1.27 d and 1.30 d (6H, CHMe2, J 7 Hz), 1.87 s and
1.90 s (3H, OAc), 2.04 s (3H, OAc), 2.12 and 2.15
s (3H, 21-Me), 3.04 (1H, CHMe2), 4.60 m (1H,
H3), 5.38 m (1H, H6), 5.80 d (1H, H16, J 5 Hz),
5.98 s and 6.02 s (1H, H4 ). IR spectrum (film,
(17Z)-3 -Acetoxy-16 -hydroxy-20-(3-isopropyl-
isoxazol-5-yl)pregna-5,17-diene.
mp
58 61 C
1
(crystals obtained by grinding with hexane). H NMR
spectrum ( , ppm): 0.98 s (3H, 18-Me), 1.02 s (3H,
19-Me), 1.30 d (6H, CHMe2, J 7 Hz), 2.04 s (3H,
OAc), 2.12 s (3H, 21-Me), 3.05 (1H, CHMe2), 4.60
m (1H, C3H3), 4.82 d (1H, 6H16, J 5 Hz), 5.38 m
1
cm ): 2975, 2960, 2915, 2880, 1745, 1595, 1580,
1470, 1460, 1425, 1380, 1250.
24-N-acetamido-3 , 16 -diacetoxycholesta-
5,17,23-trien-22-one (XIII) was obtained from the
mixture of the two isomers of 17,23-dien-24-amino-
16-ol XII as a mixture of 17(20)-isomers. Oily
(1H, C6H6), 5.97 s (1H, H4 ). IR spectrum (cm ):
1
3440, 2980, 2960, 2915, 2880, 1745, 1680, 1590,
1470, 1460, 1425, 1380, 1240.
1
substance H NMR spectrum ( , ppm): 0.97 s and
By the above procedure from 0.07 g of isoxazole
Xb was obtained 0.035 g (50%) of compound XII.
(17Z)-24-Amino-3 -acetoxy-16 -hydroxycholesta-
1.05 s (3H, 18-Me), 1.02 s (3H, 19-Me), 1.13 d (6H,
CHMe2, J 7 Hz), 1.89 s and 1.97 s (3H, 21-Me),
2.05 s (3H, OAc), 2.16 s (3H, NAc), 3.92 m (1H,
H25), 4.62 m (1H, H3), 5.38 m (1H, H6), 5.50 s and
5.52 s (1H, H23), 5.72 and 5.86 br.s (1H, H16),
5,17,23-trien-22-one
(XII).
mp
165 167 C
1
(methanol). H NMR spectrum ( , ppm): 0.92 s (3H,
18-Me), 1.04 s (3H, 19-Me), 1.20 d (6H, CHMe2, J
7 Hz), 2.03 s (3H, 21-Me), 2.04 s (3H, OAc), 4.42 d
(1H, H16, J 5 Hz), 4.62 m (1H, H3), 5.18 s ( 1H,
H23), 5.38 m (1H, H6), 5.24 br. s (1H, H16), 10.08 s
1
12.54 s (1H, NH). IR spectrum (film cm ): 2975,
2950, 2870, 1745, 1620, 1600, 1530, 1470, 1450,
1380, 1260.
1
(1H, NH). IR spectrum (cm ): 3420, 3200, 2980,
REFERENCES
2960, 2920, 2880, 1740, 1620, 1530, 1480, 1450,
1380, 1260. UV spectrum [EtOH, max, nm ( )]:
318 (6700).
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Acetylation of secondary steroid alcohols. In
1 ml of pyridine was dissolved 0.16 mmol of steroid
alcohol and thereto was added dropwise 0.5 ml of
acetic anhydride. The reaction mixture was left
standing for 18 20 h, then was treated with water,
and the reaction products were extracted into ether.
The extract was washed with 0.5% solution of hydro-
chloric acid till neutral, dried with anhydrous
sodiumsulfate, and the solvent was evaporated. The
residue was dissolved in a little of chloroform and
purified by filtration through a silica gel bed. Yields
of acetates 95 97%.
(20S)-3 -Acetoxy-20-hydroxy-20-(3-isopropyl-
isoxazol-5-yl)-16 ,17 -epoxypregna-5-ene (V) was
prepared from alcohol IV. mp 185 186 C (methanol).
1H NMR spectrum ( , ppm): 0.90 s (3H, 18-Me),
0.98 s (3H, 19-Me), 1.28 d (6H, CHMe2, J 7 Hz),
1.68 s (3H, 21-Me), 2.02 s (3H, OAc), 3.06 m (1H,
CHMe2), 3.56 s (1H, H16), 4.58 m (1H, H3), 5.36
m (1H, H6), 6.14 s (1H, H4 ). IR spectrum (KBr,
1
cm ): 3460, 2980, 2950, 2870, 1745, 1475, 1460,
1380, 1260. Mass spectrum (m/z): 331, 310, 279,
270.
(17E,Z)-3 ,16 -Diacetoxy-20-(3-isopropylisox-
azol-5-yl)pregna-5,17-diene (XI) was prepared from
16-hydroxysteroid X as a mixture of two isomers. mp
1
197 199 C (methanol). H NMR spectrum ( , ppm):
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 6 2001