Synthesis of some novel 4-acyl-3-oxo-4-aza-5-pregnene-20E-oxime ester derivatives as potent 5α-reductase inhibitors

Article abstract of DOI:10.3184/174751914X13983475274161

3-Oxo-4-aza-5-pregnene-20E-oxime was synthesised from the starting material progesterone through oxidative ring cleavage, amination ring closure and oximation. The configuration of the oxime was determined from the 2D-NOESY spectrum. A series of oxime ester derivatives were obtained through the acylation of the oxime, their structures were confirmed by ESI-MS, ¹H NMR, ¹³C NMR and HRMS.

Full text of DOI:10.3184/174751914X13983475274161

334 RESEARCH PAPER
VOL. 38 JUNE, 334–336
JOURNAL OF CHEMICAL RESEARCH 2014
Synthesis of some novel 4‑acyl‑3‑oxo‑4‑aza‑5‑pregnene‑20E‑oxime ester
derivatives as potent 5α‑reductase inhibitors
Shao‑Rui Chen*, Feng‑Juan Shen and Sheng‑Qian Liu
College of Science, Hebei University of Science and Technology, Shijiazhuang 050018, P.R. China
3-Oxo-4-aza-5-pregnene-20E-oxime was synthesised from the starting material progesterone through oxidative ring cleavage,
amination ring closure and oximation. The configuration of the oxime was determined from the 2D-NOESY spectrum. A series of
oxime ester derivatives were obtained through the acylation of the oxime, their structures were confirmed by ESI-MS, 1H NMR,
13C NMR and HRMS.
Keywords: progesterone, oxime, 5α‑reductase inhibitors
Benign prostatic hypertrophy (BPH) is known to be caused by
excessive accumulation of dihydrotestosterone, which is formed
from testosterone by testosterone 5α‑reductase.1–4 In previous
work, various 4‑aza compounds such as finasteride have been
synthesised and tested against 5α‑reductase.5,6 Finasteride
was the first inhibitor approved in the USA for the treatment
of BPH and prostate cancer. Previous studies showed that the
introduction of an oxime into the side chain would enhance
5α‑reductase inhibitory activity.7 Our group has demonstrated
that 3‑oxo‑4‑aza‑5‑androstene‑17‑oxime‑ester derivatives
showed 5α‑reductase inhibitory activity.8 Nevertheless, due to
the increase in bone and muscle loss, impotency and occurrence
of resistant prostate tumours9, it is important to seek for other
potent and specific molecules with lower side effects. On the
basis of the previous work, we now report the synthesis of novel
4‑acyl‑3‑oxo‑4‑aza‑5‑pregnene‑20E‑oxime‑ester derivatives.
The synthesis of 4‑acyl‑3‑oxo‑4‑aza‑5‑pregnene‑20E‑
oxime ester derivatives is shown in Scheme 1. Starting from
progesterone (1), oxidative cleavage of ring A was achieved
using sodium periodate and potassium permanganate to give
5,20‑dioxo‑A‑nor‑3,5‑secopregnane‑3‑oic acid (2) with the
yield of 92.2%.10,11 Ozonolysis of progesterone followed by
oxidative work‑up (H2O2–NaOH) also produced compound 2,
but the yield was 80.2% and the procedure was complex.12 This
compound was treated with ammonium acetate to afford 4‑aza‑
5‑pregnene‑3,20‑dione (3) in 89.7% yield.13 This was converted
into its 20‑oxime analogue 4 in 67.1% yield using hydroxylamine
in the presence of pyridine.14 In the IR spectrum of 4, the
characteristic oxime bands were observed at 3402 cm–1 (OH)
and 1,654 cm–1 (C=N). In the 13C NMR spectrum of compound
4 at the same time, the 20‑C=O carbon peak (209.4 ppm) of
compound 3 was replaced by the 20‑C=NOH carbon peak at
155.5 ppm. Furthermore, the structure of 4 was confirmed by
the ESI mass spectra. When the ethanol was used as the solvent,
the oxime that was produced was different from compound 4,
and was another oxime. The configuration of the 20‑oxime
(4) was determined based on the 2D‑NOESY spectrum. The
NOESY spectrum of compound 4 exhibited correlation peaks
between the 21‑CH3 (1.74 ppm) and the proton 20‑oxime group
(10.35 ppm), and consequently compound 4 was identified as
the E‑isomer. Because the 20‑oxime has an active hydrogen,
the exchange peak also appeared in the spectrum, which
decreased the strength of the NOE. In the etherification of
compound 4, the reaction rate was faster than the rate of using
O
O
O
NaIO4
CH3COONH4
CH3COOH
KMnO4
O
O
N
H
O
O
OH
3
2
1
OCOR
OH
N
N
NH2OH.HCl
RCOCl
Py
Py
O
N
O
N
H
COR
4
5
5a, R=CH3; 5b, R=CH2CH3; 5c, R=Ph; 5d, R=PhCH3; 5e, R=PhOCH3; 5f, R=PhCl; 5g, R=PhNO2
Scheme 1
* Correspondent. E‑mail: sjz_wgq@126.com
JCR1402504_FINAL.indd 334
10/06/2014 09:23:38

335 JOURNAL OF CHEMICAL RESEARCH 2014
JOURNAL OF CHEMICAL RESEARCH 2014 335
dried over anhydrous sodium sulfate, and evaporated under reduced
pressure. The residue was purified by column chromatography
on silica gel. Elution with petroleum ether/ethyl acetate afforded
compound 4 (3.2 g, 60.7%) as a white solid. m.p. 230–231 °C; IR
(KBr), n/cm–1: 3350, 2928, 1654, 1368, 1217., 930; ESI‑MS (m/z): 331.4
( M + H )+; 1H NMR (500 MHz, DMSO) δ 0.58 (s, 3H, 18‑CH3), 1.02 (s,
3H, 19‑CH3), 1.74 (s, 3H, 21‑CH3), 5.31 (s, 1H, 6‑H), 9.71 (s, 1H, 4‑NH),
10.35 (s, 1H, –OH); 13C NMR (125 MHz, DMSO) δ 162.3, 155.5, 142.3,
101.3, 56.6, 55.8, 48.5, 43.6, 38.4, 36.2, 31.3, 31.2, 29.8, 28.9, 24.2, 23.1,
21.1, 19.3, 15.7, 13.6. HRMS (ESI) calcd for C20H30N2O2Na [M+Na]+
353.2205; found: 353.2208.
Another oxime: 3-oxo-4-Aza-5-pregnene-20Z-oxime: The procedure
was the same as that for the preparation of compound 4 except for
the substitution of pyridine by ethanol. Triethylamine was added to
neutralise the acid. The structures of the second oxime was confirmed
by IR, NMR and HRMS. Yield 79.3%; m.p. 243–245 °C; IR (KBr), n/
cm–1: 3316, 2928, 1664, 1368, 1056; ESI‑MS (m/z): 331.4 (M+H)+; 1H
NMR (500 MHz, DMSO) δ 0.58 (s, 3H, 18‑CH3), 0.99 (s, 3H, 19‑CH3),
1.73 (s, 3H, 21‑CH3), 4.84 (s, 1H, 6‑H), 9.27 (s, 1H, 4‑NH), 10.34 (s,
1H, –OH); 13C NMR (125 MHz, DMSO) δ 168.3, 155.5, 141.3, 101.6,
56.6, 55.9, 48.2, 43.6, 38.4, 34.0, 31.3, 31.8, 31.7, 29.7, 28.7, 24.3, 23.1,
21.0, 19.0, 15.7, 13.6. HRMS (ESI) calcd for C20H30N2O2Na [M+Na]+
353.2205; found: 353.2209.
the other oxime because of the influence of steric hindrance.
This indirectly confirmed the configuration of compound 4.
Compound 4 was then treated with acyl chlorides in a mixture
of pyridine and dichloromethane as a solvent to afford the
4‑acyl‑3‑oxo‑4‑aza‑5‑pregnene‑20E‑oxime ester derivatives.15
The ESI mass spectra of 5a–g were characterised by their
molecular ion peaks. The 1H NMR spectrum of 5c for example,
displayed four peaks at 8.02, 7.95, 7.28 and 7.25, which were
assigned to the protons on the benzene ring. The expected
signals for the 18‑CH3 (δ=0.78 ppm), 19‑CH3 (δ=1.58 ppm),
Ph–CH3 (δ=2.43 ppm) and double bond (δ=5.24 ppm) were
observed. In its 13C NMR spectrum, the characteristic signals
of ester (–OCO–), lactam (–CON–), amide (–NCO–), and
oxime (–C=N–O–) appeared at 166.39 ppm, 163.91 ppm,
163.06 ppm, and 162.28 ppm, respectively. Also, 13C NMR
spectrum showed signals for the benzene ring and double bond
at 145.15, 143.81, 141.59, 140.52, 130.16, 129.55, 129.44, 129.20,
126.72, 101.40 ppm. The structure of 5c was further confirmed
by HRMS spectra.
In conclusion, seven novel 4‑acyl‑3‑oxo‑4‑aza‑5‑pregnene‑
20E‑oxime ester derivatives were synthesised. Their structures
1
were characterised by ESI‑MS, H NMR, 13C NMR, HRMS.
All these compounds are useful for further study for their 5α‑
reductase inhibitory activity.
4-Acyl-3-oxo-4-Aza-5-pregnene-20E-oxime-ester derivatives (5a–g);
general procedure
A stirred solution of compound 4 (0.21 g, 0.64 mmol) in a mixture
of pyridine (3 mL) and dichloromethane (3 mL) was treated with the
acyl chloride (1.92 mmol) at 0 °C. The mixture was then stirred for
0.5 h at room temperature, poured into water (10 mL), extracted with
dichloromethane (20 mL×3). The organic layer was washed with
dilute hydrochloric acid, saturated sodium carbonate solution, brine,
dried over anhydrous sodium sulfate, and evaporated under reduced
pressure. The crude product was purified by column chromatography
on silica gel. Elution with petroleum ether/ethyl acetate afforded
compounds 5a–g as white solids.
4-Acetyl-3-keto-4-Aza-5-pregnene-20E-oxime-N-O-acetate (5a):
Yield 64.1%; m.p. 175–176 °C; ESI‑MS (m/z): 415.3 (M+H)+; 1H NMR
(500 MHz, CDCl3) δ 0.61 (s, 3H, 18‑CH3), 1.18 (s, 3H, 19‑CH3), 1.89 (s,
3H, 21‑CH3), 2.11 (s, 3H, –OCO–CH3), 2.21 (s, 3H, 4‑N–CO–CH3),
5.08 (s, 1H, 6‑H); 13C NMR (125 MHz, CDCl3) δ 169.24, 166.75, 166.10,
162.05, 141.39, 101.43, 60.09, 56.67, 55.84, 48.26, 44.05, 38.18, 37.09,
31.16, 29.43, 29.05, 24.09, 23.10, 22.80, 19.89, 18.95, 18.18, 16.99, 13.37;
HRMS (ESI) calcd for C24H34N2O4Na [M+Na]+ 437.2416.; found:
437.2419.
4-Propionyl-3-oxo-4-Aza-5-pregnene-20E-oxime-N-O-propionate
(5b): Yield 57.6%; m.p. 180–182 °C; ESI‑MS (m/z): 465.3 (M+Na)+;
1H NMR (500 MHz, CDCl3) δ 0.59 (s, 3H, 18‑CH3), 1.16 (s, 3H,
19‑CH3), 1.89 (s, 3H, 21‑CH3), 2.19 (m, 2H, –OCOCH2), 2.24 (m, 2H,
4‑NCOCH2), 5.08 (s, 1H, 6‑H); 13C NMR (125 MHz, CDCl3) δ 169.25,
166.75, 166.17, 162.35, 141.35, 101.63, 60.19, 56.67, 55.64, 48.24, 44.25,
38.18, 37.59, 31.16, 29.40, 29.15, 24.12, 23.16, 22.81, 19.86, 18.96, 18.98,
16.79, 13.37, 10.1, 9.50; HRMS (ESI) calcd for C26H38N2O4Na [M+Na]+
465.2729; found: 437.2735.
4-Benzoyl-3-oxo-4-Aza-5-pregnene-20E-oxime-N-O-benzoate (5c):
Yield 54.6%; m.p. 260–262 °C; ESI‑MS (m/z): 477.9 (M+K)+; 1H NMR
(500 MHz, CDCl3) δ 0.79 (s, 3H, 18‑CH3), 1.58 (s, 3H, 19‑CH3), 2.10 (s,
3H, 21‑CH3), 5.25 (s, 1H, 6‑H), 7.45–7.51 (m, 4H, Ph), 7.58–7.66 (m, 2H,
Ph), 8.06–8.08 (m, 2H, Ph), 8.13–8.14 (m, 2H, Ph); 13C NMR (125 MHz,
CDCl3) δ 167.60, 163.83, 163.03, 162.24, 141.57, 134.20, 133.11, 130.12,
129.52, 128.75, 128.51, 101.44, 56.84, 55.89, 48.35, 48.33, 44.24, 38.24,
37.30, 37.28, 31.22, 31.20, 29.47, 29.27, 29.25, 24.17, 23.23, 20.86, 19.04,
17.14, 13.89, 13.49; HRMS (ESI) calcd for C34H38N2O4Na [M+Na]+
561.2729; found: 561.2735.
Experimental
All the reagents were obtained commercially and used without further
purification. Melting points were measured on a X4 apparatus and are
uncorrected. IR spectra were determined as KBr pellets on a FTS‑135
spectrophotometer. H NMR and 13C NMR spectra were measured
with a Varian INOVA 500 spectrometer at 500 MHz in CDCl3 as the
solvent with TMS as the internal standard. ESI‑MS were performed
on LCQ Advantage MAX spectrometer. HRMS were recorded on a
MicrOTOF‑QII10204 spectrometer.
1
5,20-Dioxo-A-nor-3,5-secopregnane-3-oic acid (2):A mixture of
progesterone (7.0 g, 22.3 mmol) in tert‑butanol (220 mL), anhydrous
sodium carbonate (2.85 g, 26.8 mmol) and H2O (10 mL) was heated
to reflux. A solution of sodium periodate (28.6 g, 133.8 mmol) and
potassium permanganate (0.2 g, 1.3 mmol) in hot water (150 mL) was
added dropwise to the refluxing reaction mixture. It was then refluxed
for another 1 h. All the inorganic material was filtered off, and washed
with water and dichloromethane. The filtrate was acidified with dilute
hydrochloric acid and extracted with dichloromethane (50 mL×3). The
organic layer was washed with brine, dried over anhydrous sodium
sulfate, and evaporated under reduced pressure. Compound 2 (6.8 g,
92.2%) was obtained as a pale yellow solid, which was used directly
without further purification; m.p. 176–178 °C (lit.12 177–179 °C). IR
(KBr), ν/cm−1: 3148 (OH), 1734 (CO), 1698 (3‑CO); ESI‑MS m/z: 333
(M‑H)–; 1H NMR (CDCl3, 500 MHz), δ 2.13 (3H, s, 21‑CH3), 1.13 (3H, s,
19‑CH3), 0.69 (3H, s, 18‑CH3).
4-Aza-5-pregnene-3,20-dione (3): The mixture of 5,20‑dioxo‑A‑
nor‑3,5‑secopregnane‑3‑oic acid (10.0 g, 29.9 mmol), ammonium
acetate (7.0 g, 90.9 mmol) in acetic acid (100 mL) was heated to reflux
for 4 h. After removal of the acetic acid under reduced pressure,
the residue was poured into water. The precipitate was filtered and
washed with water to give 3 (8.5 g, 89.7%) as pale yellow solid. m.p.
273–275 °C (lit.16 274–276 °C16). IR (KBr), ν/cm–1: 2938 (–NH), 1702
(20‑C=O), 1667 (3‑C=O); ESI‑MS (m/z): 316.4 (M+H)+; 1H NMR
(CDCl3, 500 MHz) δ 0.65 (s, 3H, 18‑CH3), 1.08 (s, 3H, 19‑CH3), 2.15 (s,
3H, 21‑CH3), 4.85 (m, 1H, 6‑H), 7.76 (s, 1H, 4‑H);13C NMR (125 MHz,
DMSO) δ 209.4, 169.3, 140.0, 103.0, 63.5, 56.6, 47.8, 44.0, 38.5, 34.3,
31.6, 31.5, 31.4, 29.6, 28.5, 24.4, 22.8, 21.0, 18.7, 13.3.
3-Oxo-4-aza-5-pregnene-20E-oxime (4): A stirred solution of 4‑aza‑
5‑pregnene‑3,20‑dione (5.0 g, 15.8 mmol) in pyridine (120 mL) was
treated with hydroxylamine hydrochloride (3.7 g, 48.6 mmol), and
stirred for 12 h at 80–90 °C, poured into water (150 mL), extracted with
dichloromethane (50 mL×3). The organic layer was washed with brine,
4-p-Methylbenzoyl-3-oxo-4-Aza-5-pregnene-20E-oxime-N-O-p-
methylbenzoate (5d): Yield 51.9%; m.p. 188–189 °C; ESI‑MS (m/z):
605.5 (M+K)+; 1H NMR (500 MHz, CDCl3) δ 0.78 (s, 3H, 18‑CH3), 1.58
(s, 3H, 19‑CH3), 2.09 (s, 3H, 21‑CH3), 2.43 (s, 6H, 2Ph‑CH3), 5.24 (s,
JCR1402504_FINAL.indd 335
10/06/2014 09:23:38

336 JOURNAL OF CHEMICAL RESEARCH 2014
1H, 6‑H), 7.25–7.30 (m, 4H, Ph), 7.95–7.96 (m, 2H, Ph), 8.01–8.03 (m,
2H, Ph); 13C NMR (125 MHz, CDCl3) δ 167.39, 163.91, 163.08, 162.24,
145.15, 143.81, 141.60, 140.53, 130.16, 129.55, 129.44, 129.20, 126.72,
101.40, 56.83, 55.90, 48.36, 48.35, 44.23, 38.24, 37.28, 37.27, 31.22,
31.20, 29.48, 29.46, 29.26, 29.25, 24.17, 23.22, 21.83, 21.70, 20.85, 19.02,
17.09, 13.49; HRMS (ESI) calcd for C36H42N2O4Na [M+Na]+ 589.3042;
found: 589.3048.
The authors appreciate the financial support from the Natural
Science Foundation of Hebei Province (B2012208036,
B2013208016), XiaoLi Foundation of Hebei University of
Science and Technology (XL201262).
Received 3 March 2014; accepted 27 March 2014
Paper 1402504 doi: 10.3184/174751914X13983475274161
Published online: 10 June 2014
4-p-Methoxybenzoyl-3-oxo-4-Aza-5-pregnene-20E-oxime-N-O-p-
methoxybenzoate (5e): yield 48.7%; m.p. 186–188 °C; ESI‑MS (m/z):
1
637.4 (M+K)+; H NMR (500 MHz, CDCl3) δ 0.78 (s, 3H, 18‑CH3),
1.55 (s, 3H, 19‑CH3), 2.08 (s, 3H, 21‑CH3), 3.87 (s, 3H, Ph‑OCH3), 3.88
(s, 3H, Ph‑OCH3), 5.24 (s, 1H, 6‑H), 6.93–6.97 (m, 4H, Ph), 8.2–8.04
(m, 2H, Ph), 8.08–8.10 (m, 2H, Ph); 13C NMR (125 MHz, CDCl3) δ
167.19, 164.35, 163.60, 163.49, 162.70, 162.33, 141.62, 140.57, 132.30,
131.56, 121.75, 114.07, 113.79, 101.39, 56.83, 55.89, 55.56, 55.47, 48.36,
48.12, 44.22, 38.23, 37.04, 37.03, 31.22, 31.20, 29.49, 29.48, 29.26,
24.17, 23.22, 21.69, 20.84, 19.02, 17.07, 13.45; HRMS (ESI) calcd for
C36H42N2O6Na [M+Na]+ 621.2941; found: 621.2944.
4-p-Chlorobenzoyl-3-oxo-4-Aza-5-pregnene-20E-oxime-N-O-p-
chlorobenzoate (5f): Yield 49.7%; m.p. 170–172 °C; ESI‑MS (m/z):
645.4 (M+K)+; 1H NMR (500 MHz, CDCl3) δ 0.78 (s, 3H, 18‑CH3), 1.55
(s, 3H, 19‑CH3), 2.08 (s, 3H, 21‑CH3), 5.21 (s, 1H, 6‑H), 7.43–7.45 (m,
4H, Ph), 7.99–8.01 (m, 4H, Ph); 13C NMR (125 MHz, CDCl3) δ 167.93,
163.13, 162.40, 162.31, 141.68, 140.96, 139.71, 131.02, 129.29, 129.01,
128.07, 101.58, 56.95, 56.01, 48.44, 48.43, 44.38, 38.34, 37.45, 37.36,
31.34, 31.32, 29.57, 29.55, 29.36, 29.35, 24.28, 23.36, 20.98, 19.16, 17.26,
13.62; HRMS (ESI) calcd for C34H36ClN2O4Na [M+Na]+ 629.1950;
found: 629.1951.
4-p-Nitrobenzoyl-3-oxo-4-Aza-5-pregnene-20E-oxime-N-O-p-
nitrobenzoate (5g): Yield 40.1%; m.p. 221–223 °C; ESI‑MS (m/z): 651.3
( M + Na)+; 1H NMR (500 MHz, CDCl3) δ 0.80 (s, 3H, 18‑CH3), 1.45 (s,
3H, 19‑CH3), 2.12 (s, 3H, 21‑CH3), 5.22 (s, 1H, 6‑H), 8.23–8.25 (m,
2H, Ph), 8.32–8.34 (m, 6H, Ph); 13C NMR (125 MHz, CDCl3) δ 167.89,
164.35, 163.60, 162.38, 141.68, 140.96, 139.71, 132.36, 131.02, 129.24,
129.01, 128.07, 115.01, 101.58, 56.95, 56.21, 48.43, 48.40, 44.38, 38.35,
37.39, 37.34, 31.34, 31.32, 29.58, 29.45, 29.33, 29.35, 24.18, 23.25, 20.98,
19.10, 17.16, 13.42; HRMS (ESI) calcd for C34H36ClN2O4Na [M+Na]+
651.2431; found: 651.2436.
References
1
2
3
J.A.R. Salvador, R.M.A. Pinto and S.M. Silvestre, J. Steroid Biochem.
Molec. Biol., 2013, 137, 199.
M. Garrido, E. Bratoeff, D. Bonilla, J. Soriano, Y. Heuze and M. Cabeza,
J. Steroid Biochem. Molec. Biol., 2011, 127, 367.
C. Amaral, C. Varela, G. Correia‑da‑Silva, E. Tavares da Silva, R.A.
Carvalho, S.C.P. Costa, S.C. Cunha, J.O. Fernandes, N. Teixeira and F.M.F.
Roleira, Biochimie, 2013, 95, 2097.
4
5
S. Aggarwal, S. Thareja, T.R. Bhardwaj, J. Haupenthal, R.W. Hartmann
and M. Kumar, Eur. J. Med. Chem., 2012, 54, 728.
S.O. Lorente, C.J. Jimenez, L. Gros, V. Yardley, K. de Luca‑Fradley, S.L.
Croft, J.A. Urbina. L.M. Ruiz‑Perez, D.G. Pacanowska and I.H. Gibert,
Bioorg. Med. Chem., 2005, 13, 5435.
6
R.L. Tolman, S.P. Sahoo, R.K. Bakshi, D. Gratale, G. Patel, S. Patel, J.
Toney, B. Chang and G.S. Harris, J. Steroid Biochem. Molec. Biol., 1997,
60, 303.
7
8
9
R.W. Hartmann, M. Hector, S. Haidar, P.B. Ehmer, W. Reichert and J. Jose,
J. Med. Chem., 2003, 43, 4266.
X.D. Wu, D.Z. Liu, X.Q. Zhou, X.W. Yang and K.M. Zhu, Acta Chim.
Sinica, 2009, 67, 1487.
A. Guarna, C. Belle, F. Machetti, E.G. Occhiato and A.H. Payne, J. Med.
Chem., 1997, 40, 1112.
10 J.W. Morzycki, Z. Lotowski, A.Z. Wilczewska and J.D. Stuart, Bioorg.
Med. Chem., 1996, 4, 1209.
11 S. Kim and E. Ma, Molecules, 2009, 14, 4655.
12 G.H. Rasmusson, G.F. Reynolds, T. Utne, R.B. Jobson, R.L. Primka, C.
Berman and J.R. Brooks, J. Med. Chem., 1984, 27, 1690.
13 Z.X. Jiang, J.Q. Ye, L. Jiang and Y.S. Zhao, Steroids, 2005, 70, 690.
14 S.R. Chen, X.Q. Zhou, W. Li and D.Z. Liu, Chem. Res. Chinese
Universities, 2011, 27, 604.
15 S.R. Chen and D.Z. Liu, J. Chem. Res., 2011, 35, 453.
16 M. Borthakur and R.C. Boruah, Steroids, 2008, 73, 637.
JCR1402504_FINAL.indd 336
10/06/2014 09:23:38

Copyright of Journal of Chemical Research is the property of Science Reviews 2000 Ltd. and
its content may not be copied or emailed to multiple sites or posted to a listserv without the
copyright holder's express written permission. However, users may print, download, or email
articles for individual use.