Synthesis and Biological Evaluation of Novel Steroidal 5α,8α-Endoperoxide Derivatives with Aromatic Hydrazone Side Chain as Potential Anticancer Agents

Article abstract of DOI:10.1134/S1068162019060396

Abstract: Seven new steroidal 5α,8α-endoperoxide derivatives with C-17 aromatic hydrazone side chain were synthesized. Structures of the synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectrometry. Anti-proliferative activities of the synthesized compounds were evaluated in vitro by the MTT method. Among the seven compounds, 5α,8α-epidioxy-17-(4-chloro-benzylidene)-hydrazonoandrost-3β-ol showed the strongest anti-proliferative activity against three human cancer cell lines (MCF-7, HepG2, and SK-Hep1).

Full text of DOI:10.1134/S1068162019060396

ISSN 1068-1620, Russian Journal of Bioorganic Chemistry, 2019, Vol. 45, No. 6, pp. 585–590. © Pleiades Publishing, Ltd., 2019.
Synthesis and Biological Evaluation of Novel Steroidal
5
α,8α-Endoperoxide Derivatives with Aromatic Hydrazone Side
Chain as Potential Anticancer Agents
a
a, 1
a
a
b
H. J. Wang , M. Bu , J. Wang , L. Liu , and S. Zhang
a
College of Pharmacy, Qiqihar Medical University, Qiqihar, 161006 China
b
Basic Medical Science College, Qiqihar Medical University, Qiqihar, 161006 China
Received April 29, 2019; revised May 25, 2019; accepted July 25, 2019
Abstract—Seven new steroidal 5α,8α-endoperoxide derivatives with C-17 aromatic hydrazone side chain
1
13
were synthesized. Structures of the synthesized compounds were characterized by IR, H NMR, C NMR,
and mass spectrometry. Anti-proliferative activities of the synthesized compounds were evaluated in vitro by
the MTT method. Among the seven compounds, 5α,8α-epidioxy-17-(4-chloro-benzylidene)-hydrazonoan-
drost-3β-ol showed the strongest anti-proliferative activity against three human cancer cell lines (MCF-7,
HepG2, and SK-Hep1).
Keywords: steroid, ergosterol peroxide, dehydroepiandrosterone, dihydrazone, antitumor activity
DOI: 10.1134/S1068162019060396
INTRODUCTION
novel steroidal endoperoxide derivatives that contain a
5
α,8α-peroxy bond and dihydrazone unit attached to
Nowadays, natural products have attracted exten-
sive attention in health promotion and disease treat-
ment, including cancer therapy. Natural product-
based drug discovery is a major route leading to devel-
oping therapeutic drugs for various disease [1]. Ergos-
terol peroxide (5α,8α-epidioxyergosta-6,22-diene-
C-17 of the D-ring system as side-chain. Anti-prolifer-
ative activities of the derivatives were evaluated against
three human cancer cell lines in vitro.
RESULTS AND DISCUSSION
3
β-ol, EP; Fig. 1), is a metabolite of a series of natural
The general procedure for the synthesis of steroidal
sterol endoperoxide derivatives; it has been isolated
from many kinds of medicinal fungi [2–4]. Plenty of
studies have been reported indicating that ergosterol
peroxide can inhibit cancer cells growth through cyto-
toxicity or anti-angiogenesis [5–11].
5
α,8α-endoperoxide derivatives with C-17 aromatic
hydrazone is shown in Scheme 1. Dehydroepiandros-
terone (I) as starting material was acetylized with ace-
tic anhydride to give compound (II), which then
underwent bromination and debromination with
Steroidal compounds have always been widely
applied in the field of medicine as anti-inflammatory,
contraceptive, diuretic, and anticancer agents [12–
5,7
NBS, n-Bu NBr, and n-Bu NF to afford Δ -diene
4
4
acetate (III). Subsequently, compound (III) was con-
verted to compound (IV) via deacetylation reaction
1
4]. The special skeleton features of steroidal mole-
cules provide additional fascination for us to design
and synthesize new entities with the potential to
become promising drugs [15, 16]. On the other hand,
hydrazine and its analogues have also been demon-
strated to exhibit wide range of activities, including
antibacterial, antivirus, and antitumor ones [17–19].
Especially, some novel steroidal hydrazone analogues
also presented obviously pharmaceutical activities
[
20–25].
O
O
In the present work, as a part of our search for novel
potential anticancer agents related to peroxide steroi-
dal derivatives [26–28], we report the synthesis of
HO
1
Corresponding author: e-mail: buming@qmu.edu.cn.
Fig. 1. Ergosterol peroxide (EP).
585

5
86
WANG et al.
with potassium hydroxide in 30% overall yield from compound (V) with hydrazine hydrate yielded the cor-
compound (I). The key compound (IV) was converted responding steroidal hydrazine (VI). At last, the reac-
to endoperoxide (V) through photooxidation reaction tion of steroidal hydrazine (VI) with different aromatic
with eosin as photosensitizer. Then, the reactions of aldehydes gave our target compounds (VIIa–g).
19
O
O
O
O
12
1
8
1
1
13 17
14
16
H
1
4
i
ii
iii
2
9
1
0
8
15
7
HO 3
5
HO
AcO
AcO
6
(I)
(II)
(III)
(IV)
2'
20
1'
NH2
3'
O
N
N
N
2''
4'
R
3''
iv
v
vi
O
O
O
O
O
O
HO
HO
HO
(V)
(VI)
(VIIa)−(VIIg)
(
VII) R =4-H (a), 4-F (b), 4-Clr (c), 4-Br (d), 4-t-butyl (e), 4-CN (f), 4-OCH (g)
3
Scheme 1. Synthesis of novel 5α,8α-peroxide steroid derivatives (VIIa–g). Reagents and conditions: (i) Ac O, pyridine,
2
DCM, rt; (ii) cyclohexane, NBS, reflux, 1 h; (iii) NaOMe, MeOH, reflux, 1 h; Bu NF, THF, rt, 12 h; (iv) pyridine, O ,
4
2
light, 0°C, 0.5 h; (v) NH NH –H O, EtOH, 45°C,1 h; (vi) EtOH, AcOH, aromatic aldehydes, rt, 1–2 h
2
2
2
The structures of compounds (VIIa–g) were con- the side chain of the compounds enhanced the anti-
1
13
firmed by IR, H NMR, C NMR, and mass spec- proliferative activity. Compound (VIIc) with 4-Cl–
trometry. Taking compound (VIIa) as a typical exam-
C H at C-17 side chain displayed the strongest anti-
6 4
1
ple, in the H NMR spectrum, the downfield chemi- proliferative activity against human hepatocellular
cal shifts of C6-H at 6.54 ppm and C7-H at 6.32 ppm carcinoma cell lines.
demonstrate a formation of 5α,8α-peroxybond and
-CH=CH-7 bond. The stereochemistry of the per-
In summary, we have successfully prepared a series
of steroidal 5α,8α-endoperoxide derivatives with vari-
6
1
oxide was assigned by comparison of the H NMR and ous aromatic hydrazone substitutes. All the synthe-
X-ray crystal structure of ergosterol peroxide [26]. In sized compounds have been investigated for their in
addition, the resonances of C20-H shown at 8.28 ppm vitro anti-proliferative activities. From the activity
demonstrate formation of the –C=N–N=CH– bond studies, compound (VIIc) was shown to possess signif-
in compound (VIIa), which could also be demon- icant anti-proliferative activity against the tested can-
strated in the IR spectrum of compound (VIIa): the cer cell lines. The results showed that the substituent
absorption at 1654, 1611, and 1479, corresponding to changes to the side chain of EP could serve as a feasi-
the –C=N–N=C– bond is observed.
ble launch point for design of new steroidal agents.
Compounds (VIIa–g) and EP were evaluated for
their anti-proliferative activities against human tumor
cell lines (MCF-7, HepG2, SK-Hep1) by MTT assay;
cisplatin was used as a positive control. The anti-pro-
EXPERIMENTAL
Reagents were used without further purification.
1
13
liferative activity data of compounds (VIIa–g) are The H and C NMR spectra (δ, ppm, J, Hz) were
summarized by IC values in Table 1.
recorded using the Bruker Avance DRX400 spectrom-
eter (400 and 100 MHz, respectively) in CDCl or
5
0
Compared to the parent EP, most of compounds
3
(
VIIa–g) possess significant anti-proliferative activity DMSO-d . Tetramethylsilane was used as an internal
6
against all three tested cancer cell lines. Probably, the standard. Melting temperatures were determined on
electron-withdrawing properties of the substituents in an MP120 auto point apparatus. The mass spectra of
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
Vol. 45
No. 6
2019

SYNTHESIS AND BIOLOGICAL EVALUATION
587
Table 1. In vitro anti-proliferative activity data of com- in THF, 0.07 mol, 1.5 equiv.). The resulting brown
pounds (VIIa–g)
solution was stirred for 10 h, and then followed by
rotary evaporation under 45°C to a yellow solid. The
solid was diluted with DCM (100 mL), washed with
1
,2
IC , μM
5
0
Compd
water (2 × 50 mL), and dried over anhydrous Na SO .
HepG2
SK-Hep1
MCF-7
>60
2
4
Purification by column chromatography column gave
(
(
(
(
(
(
(
VIIa)
VIIb)
VIIc)
VIId)
VIIe)
VIIf)
VIIg)
49.34 ± 0.49 50.43 ± 0.88
a pale yellow solid as compound (III) (5.8 g). Yield
1
11.74 ± 0.32 16.92 ± 0.53 32.45 ± 0.50
9.24 ± 0.11 13.55 ± 0.24 21.32 ± 0.06
13.22 ± 0.26 10.14 ± 0.32 20.76 ± 0.32
35.07 ± 0.18
18.47 ± 0.14
34.25 ± 0.53 40.20 ± 0.40
15.78 ± 0.30 17.40 ± 0.24 24.43 ± 0.26
0.65 ± 0.04 2.42 ± 0.06 6.35 ± 0.15
3
5%, mp 112–115°C. H NMR (CDCl ): 5.6 (1H, s,
3
H6), 5.57 (1H, d, J 3.2, H7), 4.7 (1H, m, C3-αH),
2
.56–2.49 (2H, m, H16), 2.38 (1H, d, J 12.5, H9),
2
.24–2.17 (2H, m, H11), 2.07 (3H, s, OAc), 1.97–1.92
37.20 ± 0.62 57.61 ± 0.88
27.17 ± 0.19 39.45 ± 0.44
(
2H, m, H12), 1.74 (2H, d, J 4.8, H4), 1.70–1.58 (4H,
m,H1, H2), 1.40–1.34 (2H, m, H15), 1.27 (1H, s,
H14), 0.99 (3H, s, H18), 0.83 (3H, s, H19). MS (ESI)
>60
+
m/z: 351.7 [M + Na] .
EP
Cisplatin
3β-Hydroxyandrosta-5,7-diene-17-one (IV). To a
suspension of intermediate (III) (11 g, 0.034 mol) in
1
2
Data are the mean ± SD of three experimental results.
Human liver carcinoma cell line (HepG2, SK-Hep1), human MeOH (100 mL) 25% (wt) NaOMe in MeOH
breast adenocarcinoma cell line (MCF-7).
(10 mL) was added. The mixture was refluxed for 1 h,
then 100 mL of water was added into the mixture over
0
.5 h and it was continually stirred for 1 h. The precip-
all compounds were tested on an Esquire 6000 mass
spectrometer in ESI mode. The IR spectra (ν , cm ;
itate was collected, washed with water (50 mL), and
–
1
max
dried under high vacuum at 40°C to get a brown solid
KBr) were registered on the Equinox 55 Fourier trans- crude product. Purification by column chromatogra-
form infrared spectrometer (Bruker, Germany). Flash phy to give a pale solid as intermediate (IV) (9.3 g).
1
chromatography in the experiments was performed
using silica gel (400 mesh).
Yield 96%, mp 157–159°C. H NMR (CDCl ): 6.00
3
(
1H, d, J 9.8, H6), 5.70 (1H, d, J 9.8, H7), 4.30 (1H, t, J
7
.9, OH), 3.76–3.60 (1H, m, C3-αH), 1.03 (3H, s, H18),
3
β-Acetoxyandrosta-5-en-17-one (II). To a sus-
+
0
.96 (3H, s, H19). MS (ESI) m/z: 309.9 [M + Na] .
pension of dehydroepiandrosterone (I) (14.4 g, 0.05 mol)
in CH Cl –pyridine, 4 : 1 (80 mL), Ac O (6 mL,
2
2
2
3β-Hydroxy-5α,8α-epidioxyandrostan-17-one (V).
To a solution of intermediate (IV) (140 mg) in pyridine
0
.07 mol) was added over 15 min. The mixture was
stirred for 8 h at room temperature and then water
50 mL) was added. The resulting mixture was
extracted with EtOAc (2 × 80 mL). The combined
organic phase was washed with NaHCO saturated
(
20 mL) eosin (1 mg) was added in a quartz tube. The
(
mixture was kept in a water-cooled bath and vigor-
ously stirred by bubbling in the oxygen. At the same
time, the mixture was irradiated with an iodine tung-
3
aqueous (2 × 50 mL) and brine (2 × 50 mL) and dried sten lamp (220 V, 500 W) for 0.5 h. The solution was
over anhydrous Na SO . Evaporation of solvent gave poured into ice-cold water (20 mL) and extracted with
2
4
crude product (II) as a white solid (16 g). Yield 97.6%, ethyl acetate (2 × 50 mL). The combined organic
1
mp 168–170°C. H NMR (CDCl ): 5.40 (1H, d, J 5.0, phase was washed with brine (2 × 50 mL) and dried
3
over anhydrous Na SO . Evaporation of solvent and
H6), 4.65–4.54 (1H, m, H7), 2.45 (1H, m, H9), 2.34
2
4
(
2H, d, J 7.8, H16), 2.11 (2H, m, 2H, H11), 2.05 (3H, then purification by column chromatography (40%
s, OAc), 1.93–1.90 (2H, m, H12), 1.87–1.81 (2H, m, EA in PE) gave (V) as white needles (101.4 mg, 63%),
1
H4), 1.71–1.62 (4H, m, H1, H2), 1.55–1.49 (2H, m, mp 167.0–168.1°C. H NMR (CDCl ): 6.51 (1H, d, J
3
H15), 1.03 (3H, s, H18), 1.00 (1H, d, J 3.8, H14), 0.90 8.5, H6), 6.33 (1H, d, J 8.6, H7), 4.00 (1H, s, OH),
+
(
3H, s, H19). Mass spectrum (ESI) m/z: 353.9 [M+ Na] . 3.25–2.12 (1H, m, C3-αH), 2.58–2.47 (1H, m, H9),
2
.24–2.12 (2H, m, H16), 2.08–2.00 (2H, m, H11),
.86–1.81 (2H, m, H12), 1.72–1.62 (1H, m, H4),
.58–1.54 (4H, m, H1, H2), 1.54–1.49 (1H, m, H14),
3
β-Acetoxyandrosta-5,7-diene-17-one (III). Solu-
1
tion of intermediate (II) (16 g, 0.05 mol) in cyclohex-
ane (70 mL) was heated to 70°C for 20 min and then
NBS (12.5 g, 0.07 mol) was added. The mixture was
refluxed for 1.5 h. The mixture was diluted with
1
1
.38–1.22 (2H, m, H15), 1.00 (3H, s, H18), 0.92 (3H,
+
s, H19). MS (ESI) m/z: 319.19 [M + H] .
1
50 mL water. The precipitate was collected and
5α,8α-Epidioxy-17-hydrazonoandrostan-3β-ol (VI).
washed with water. Then the solid was dissolved in To a solution of intermediate (V) (2.0 g, 6.7 mmol) in
DCM, washed with brine, and dried over anhydrous EtOH (50 mL) 85% hydrazine hydrate (3 mL) was
Na SO . Evaporation of solvent gave a light brown added. The mixture was heated to 45°C and stirred for
2
4
solid (17.5 g, 85%). The mixture of the crude bromide 2 h. The white solid was collected by filtration. Inter-
(
17.5 g, 0.043 mol) prepared above was added into mediate (VI) was obtained as white solid (2.1 g) after
tetrabutylammonium fluoride (45 mL 1.0 M solution recrystallizing in MeOH. White powder, yield 87%,
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 45 No. 6 2019

5
88
WANG et al.
1
mp 182.5–185.6°C. H NMR (DMSO-d ): 6.50 (1H, H3', H3''), 6.55 (1H, d, J 8.2, H6), 6.33 (1H, d, J 8.2,
6
d, J 7.6, H6), 6.32 (1H, d, J 7.0, H7), 5.36 (2H, d, J H7), 4.04–3.96 (1H, m, OH), 3.65 (1H, m, C3-αH),
1
0
3
0.4, NH ), 4.68 (1H, m, OH), 3.16 (1H, m, C3-αH), 2.78–2.66 (2H, m, H16), 2.08–2.04 (1H, m, H9),
2
.99 (3H, s, H18), 0.89 (3H, s, H19). MS (ESI) m/z: 2.01–1.95 (2H, m, H11), 1.89–1.86 (2H, m, H12),
+
1
.78–1.74 (2H, m, H4), 1.62–1.56 (4H, m, H1, H2),
33.1 [M + H] .
1
.38–1.27 (2H, m, H15), 1.12 (3H, s, H18), 1.06 (1H,
Synthesis of novel derivatives (VIIa–g). General
1
3
s, H14), 0.95 (3H, s, H19). C NMR (CDCl ): 181.3
3
procedure. To a suspension of intermediate (VI) (0.2
(
(
(
C17), 156.6 (C20), 136.7 (C5), 136.4 (C4'), 132.9
C2'), 130.1 (C2''), 129.3 (C3'), 129.0 (C3''), 116.0
C1'), 115.8 (C6), 82.3 (C3), 66.3 (C14), 51.5 (C9),
mmol) in anhydrous EtOH (30 mL) various aldehydes
(
0.2 mmol) were added. The mixture was continually
stirred under 50°C for 2–3 h until no starting material
was left. Then the solvent was evaporated by rotary
evaporation. The residue was purified by flash chro-
matography to afford compounds (VIIa–g).
4
9.1 (C13), 46.0 (C4), 37.2 (C1), 36.8 (C10), 34.7
(
C12), 33.9 (C8), 30.1 (C7), 29.5 (C2), 27.8 (C15),
2
3.0 (C16), 20.3 (C11), 18.2(C19), 16.8 (C18). MS
+
(
ESI) m/z: 455.2 [M + H] .
5
α,8α-Epidioxy-17-(benzylidene)hydrazonoandrost-
3
7
(
β-ol (VIIa). White powder. Yield 61%, mp 72.5–
5α,8α-Epidioxy-17-(4-bromo-benzylidene)hydra-
1
zonoandrost-3β-ol (VIId). White crystals. Yield 60%,
4.4°C. IR: 1654, 1611, 1479 (C=N–N=C). H NMR
mp 76.4–78.7°C. IR: 1654, 1605, 1458 (C=N–N=C).
CDCl ): 8.28 (1H, s, H20), 7.54 (2H, d, J 5.7, H2',
3
1
H NMR (CDCl ): 8.23 (1H, s, H20), 7.62 (2H, d, J
H2''), 7.42 (3H, m, H3', H3'', H4'), 6.54 (1H, d, J 8.4,
3
H6), 6.32 (1H, d, J 8.2, H7), 4.08 (1H, dd, J 11.3, 5.6, 8.0, H2', H2''), 7.54 (2H, d, J 7.8, H3', H3''), 6.53 (1H,
OH), 3.99–3.96 (1H, m, C3-αH), 2.77–2.65 (2H, m, d, J 8.4, H6), 6.31 (1H, d, J 8.4, H7), 4.15–4.05 (1H,
H16), 2.20–2.10 (1H, m, H9), 2.05–1.80 (4H, m, m, OH), 4.03–3.89 (1H, m, C3-αH), 2.82–2.56 (2H,
H11, H12), 1.80–1.62 (4H, m, H4, H2), 1.48–1.43 m, H16), 2.13–2.12 (1H, m, H9), 2.05–1.95 (2H, m,
(
2H, m, H1), 1.40–1.25 (2H, m, H15), 1.11 (3H, m, H11), 1.94–1.75 (2H, m, H12), 1.74–1.74 (4H, m,
H18), 1.05 (1H, m, H14), 0.93–0.88 (3H, m, H19). H1, H2), 1.57–1.50 (2H, m, H4), 1.35–1.20 (2H, m,
1
3
H15), 1.10 (3H, s, H18), 1.05 (1H, s, H14), 0.93 (3H,
C NMR (CDCl ): 183.1 (C17), 162.2 (C20), 141.1
3
13
s, H19). C NMR (CDCl ): 181.3 (C17), 156.7 (C20),
(
(
C5), 134.6 (C4'), 130.6 (C2'), 128.8 (C2''), 128.7
3
C3'), 128.5 (C3''), 128.1 (C1'), 121.0 (C6), 71.6 (C3), 136.1 (C5), 131.9 (C4'), 130.9 (C2'), 130.0 (C2''), 129.9
5
3.7 (C14), 50.4 (C9), 44.3 (C13), 42.2 (C4), 37.2 (C3'), 129.5 (C3''), 128.8 (C1'), 115.9 (C6), 82.4 (C3),
C1), 36.8 (C10), 33.9 (C12), 31.6 (C8), 31.5 (C7), 66.3 (C14), 51.5 (C9), 49.1 (C13), 46.0 (C4), 37.2
(
3
1.3 (C2), 28.0 (C15), 23.3 (C16), 20.6 (C11), 19.5 (C1), 36.8 (C10), 34.6 (C12), 33.9 (C8), 30.1 (C7),
+
2
9.6 (C2), 27.8 (C15), 23.0 (C16), 20.3 (C11), 19.2
(
C19), 16.5 (C18). MS (ESI) m/z: 421.2 [M + H] .
+
(
C19), 18.1 (C18). MS (ESI) m/z: 500.2, 502.2 [M + H] .
5
α,8α-Epidioxy-17-(4-fluoro-benzylidene)hydra-
zonoandrost-3β-ol (VIIb). White powder. Yield 70%,
5α,8α-Epidioxy-17-(4-(t-butyl)-benzylidene)hydra-
mp 72.3–74.8°C. IR: 1647, 1601, 1508 (C=N–N=C). zonoandrost-3β-ol (VIIe). White powder. Yield 87%,
1
H NMR (CDCl ): 8.27 (1H, s, H20), 7.75–7.73 (2H, mp 91.3–92.2°C. IR: 1651, 1608, 1458 (C=N–N=C).
3
1
m, H2', H2''), 7.09–7.15 (2H, m, H3', H3''), 6.55 (1H,
H NMR (CDCl ): 8.25 (1H, d, J 7.0, H20), 7.69 (2H,
3
d, J 8.2, H6), 6.33 (1H, d, J 8.0, H7), 4.01 (1H, m, dd, J8.1, 4.5, H2', H2''), 7.44 (2H, dd, J 8.2, 2.9, H3',
OH), 3.55 (1H, m, C3-αH), 2.78–2.63 (2H, m, H16), H3''), 6.55 (1H, d, J 8.2,H6), 6.33 (1H, d, J8.4,H7),
2
(
(
.15 (1H, m, H9), 2.05–2.04 (2H, m, H11), 1.96–1.93 4.04–3.97 (1H, m, OH), 3.81–3.75 (1H, m, C3-αH),
2H, m, H12), 1.89–1.86 (2H, m, H4), 1.77–1.63 2.74–2.60 (2H, m, H16), 2.20–2.05 (1H, m, H9),
4H, m, H2), 1.63–1.56 (2H, m, H1), 1.36–1.27 (2H, 1.99–1.95 (2H, m, H11), 1.87–1.85 (4H, m, H1, H2),
m, H15), 1.13 (3H, m, H18), 1.05 (1H, s, H14), 0.94 1.78–1.77 (2H, m, H12), 1.68–1.66 (2H, m, H4),
13
(
(
(
(
3H, s, H19). C NMR (CDCl ): 181.2 (C17), 165.5 1.60–1.53 (2H, m, H15), 1.36 (9H, s, 4'-CH
3
), 1.12
3
C20), 160.8 (C5), 156.7 (C4'), 136.1 (C2'), 130.1 (1H, s, H14), 1.05 (3H, m, H18), 0.94 (3H, s, H19).
1
3
C3',C3''), 115.8 (C1'), 115.7 (C6), 82.3 (C3), 66.2
C NMR (CDCl ): 180.3 (C17), 157.5 (C20), 136.1
3
C14), 51.5 (C9), 49.1 (C13), 45.9 (C4), 37.1 (C1), (C5), 131.7 (C4'), 130.1 (C2'), 129.9 (C3'), 129.6
3
6.9 (C10), 34.7 (C12), 33.9 (C8), 30.1 (C7), 29.7 (C3''),127.9 (C2''), 125.6 (C1'),116.0 (C6), 82.3 (C3),
(
1
C2), 27.8 (C15), 23.0 (C16), 20.0 (C11), 18.1 (C19), 66.1 (C14), 51.5 (C9), 49.1 (C13), 45.9 (C4), 37.2
+
6.7 (C18). MS (ESI) m/z: 439.2 [M + H] .
(C1), 36.8 (C10), 34.9 (C12), 34.0 (C8), 31.3 (C-Bu),
3
(
0.1 (C7), 27.8 (C15), 23.0 (C16), 20.3 (C11), 18.2
5
α,8α-Epidioxy-17-(4-chloro-benzylidene)hydra-
zonoandrost-3β-ol (VIIc). Yellowish powder. Yield
3%, mp 80.5–81.3°C. IR: 1654, 1608, 1489 (C=N–
+
C19), 18.0 (C18). MS (ESI) m/z: 477.3 [M + H] .
7
5
α,8α-Epidioxy-17-(4-cyano-benzylidene)hydra-
1
N=C). H NMR (CDCl ): 8.27 (1H, s, H20), 7.71– zonoandrost-3β-ol (VIIf). Yellowish powder. Yield
3
7
.69 (2H, d, J 8.0, H2', H2''), 7.42–7.39 (2H, d, J 8.4, 81%, mp 84.6–85.8°C. IR: 1653, 1617, 1472 (C=N–
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
Vol. 45
No. 6
2019

SYNTHESIS AND BIOLOGICAL EVALUATION
COMPLIANCE WITH ETHICAL STANDARDS
.85 (2H, d, J 8.0, H2', H2''), 7.72–7.70 (2H, d, J 8.2,
The work has no studies involving humans or animals as
589
1
N=C). H NMR (CDCl ): 8.29 (1H, s, H20), 7.87–
3
7
H3', H3''), 6.56–6.53 (1H, d, J 8.4, H6), 6.35–6.33 subjects of the study.
1H, d, J 8.4, H7), 4.06–3.99 (1H, m, OH), 3.85–
(
3
2
2
.80 (1H, m, C3-αH), 2.77–2.64 (2H, m, H16),
.20–2.15 (1H, m, H9), 2.07–2.04 (1H, m, H11),
.01–1.94 (2H, m, H1, H2), 1.78–1.74 (2H, m, H12),
Conflict of Interests
Authors declare that they have no conflicts of interests.
1
.61–1.56 (2H, m, H4), 1.35–1.26 (2H, m, H15), 1.15
(
3H, s, H18), 1.06 (1H, s, H14), 0.95 (3H, s, H19);
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