Synthesis of some new steroidal [16α,17α-d]-isoxazolines

Article abstract of DOI:10.1016/j.steroids.2005.01.003

Regioselective synthesis of novel steroidal anti-inflammatory ante drug analogues, viz., [16α,17α-d]-isoxazolines 1(a-h) and 2(a-h) prepared in a single step in good yield by the reaction of 16-dehydropregnenolone acetate (16-DPA) 1 or related 21-chloro-20-oxopregnane 2 with various aldoximes (a-h) in presence of chloramine-T in refluxing ethanol.

Full text of DOI:10.1016/j.steroids.2005.01.003

Steroids 70 (2005) 494–498
Synthesis of some new steroidal [16␣,17␣-d]-isoxazolines
Pritish Chowdhury∗, Archana Moni Das, Papori Goswami1
Natural Products Chemistry Division, Regional Research Laboratory, Jorhat 785006, India
Received 29 June 2004; received in revised form 17 September 2004; accepted 4 January 2005
Available online 20 March 2005
Abstract
Regioselective synthesis of novel steroidal anti-inflammatory ante drug analogues, viz., [16␣,17␣-d]-isoxazolines 1(a–h) and 2(a–h)
prepared in a single step in good yield by the reaction of 16-dehydropregnenolone acetate (16-DPA) 1 or related 21-chloro-20-oxopregnane
2 with various aldoximes (a–h) in presence of chloramine-T in refluxing ethanol.
© 2005 Elsevier Inc. All rights reserved.
Keywords: 16-Dehydropregnenolone acetate; 21-Chloro-20-oxopregnane; Cycloaddition reactions; Steroidal [16,17-d]-isoxazolines; Topical anti-inflammatory
agents
Inter- and intra-molecular cycloaddition reactions of ni-
trones are of great significance because of their potential
flexibility to enter the complex molecular framework of many
natural products [1]. This flexibility is further enhanced by
using oximes as nitrone precursors which are potentially am-
bient nucleophiles with either nitrogen or oxygen acting as
the reaction site depending on the other factors like reagents,
solvents and pH of the reaction mixture [2]. Dipolar cycload-
dition of nitrile oxides with olefinic compounds are of syn-
thetic interest since the product isoxazolines are versatile
intermediates for the synthesis of bifunctional compounds.
The generation of nitrones leads to cycloaddition products
like isoxazolines and isoxazolidines, which have further po-
tential for synthetic manipulation. The chemistry of isoxa-
zolines continues to attract the interest because of their ring
functions as a masked aldol or unsaturated carbonyl group
[3]. The isoxazoline derivatives could be utilized in order
to regulate the stereo and regiochemistry in natural products
synthesis [4–8]. Recent works on steroids reveal that many
of the steroidal [16␣,17␣-d]-3ꢀ-carbethoxyisoxazolines have
been found to be anti-inflammatory ante-drugs [9]. The ear-
lier work of Green et al. [10] had also focussed on the top-
ical anti-inflammatory activity of some steroidal [16␣,17␣-
d]-isoxazolidines.
In steroid field there are two frequently utilized meth-
ods for generation of nitrile oxides for synthesizing steroid
fused heterocycles. The Mukaiyama method [11] is based
on the primary nitro-alkanes with phenyl isocyanate in pres-
ence of a base like triethylamine. But phenyl isocyanate be-
ing hazardous, the replacement of this method is desirable.
The other most frequently used method is a base mediated
dehydrohalogenation [12–14] of hydroxymoyl halides ob-
tained by the reaction of aldoximes with NCS, NBS, halo-
gens and 1-chlorobenzotriazole, etc. All these methods are
tedious giving moderate yield of the isoxazolines. It was en-
visaged that 1,3-dipolar addition of fulminic acid to enone
system yielded isoxazolines [15]. However, the generation
of fulminic acid is often troublesome and leads to explo-
sion if metal fulminates are used [1b]. 1,3-dipolar cycloaddi-
tion of carbethoxyformonitrileoxide (CEFNO) which is gen-
erated in situ by treatment of ethyl chloro oximido acetate
with aqueous sodium bicarbonate has also been reported.
Moerch et al. [16] had earlier investigated the reaction of 16-
dehydropregnenolone acetate (16-DPA) with ethyl chloro ox-
imidoacetateandsodiumbicarbonateandreportedstereospe-
cific formation of product giving [16␣,17␣-d]-isoxazoline
derivatives.
∗
Corresponding author. Tel.: +91 376 237 0121x532;
fax: +91 376 237 0011.
E-mail address: pritishchowdhury@yahoo.com (P. Chowdhury).
Present address: Department of Chemistry, IIT Guwahati, India.
1
0039-128X/$ – see front matter © 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.steroids.2005.01.003

P. Chowdhury et al. / Steroids 70 (2005) 494–498
495
We investigated here 1,3-dipolar cycloaddition reaction of
16-dehydro-20-oxopregnanes [17–20], viz., 16-DPA 1 and
related 21-chloro derivative 2 with the corresponding al-
doxime by in situ generation of nitrile oxide [21] through
the action of chloramine T (N-chloro-N-sodio-4-methyl ben-
zene sulfonate) in ethanol to give their corresponding isox-
azolines. The present method of synthesizing steroid-fused
heterocycles through in situ generation of nitrile oxides from
the reaction of aldoximes with chloramines-T is first of
its kind to be reported in steroid field giving high yield
of [16␣,17␣-d]-isoxazolines under simple reaction condi-
tions. The reaction took place regioselectively at the ␣,␤-
unsaturated double bond at 16, 17 position to give only
[16,17-d]-isoxazolines. Although earlier Culbertson et al.
[22] reported the addition of C,N-diphenyl nitrone to 16-
dehydropregnenolone acetate which gave both [16␣,17␣-d]-
and [17␣,16␣-d]-isoxazolidines, the regiospecificity of 1,3
dipolar cycloaddition to ␣,␤-unsaturated enone [10] and the
stereo specificity of the cycloaddition to 16-ene steroid sys-
tem with 17-acetyl side chain [16] are known and are gen-
erally reported to give their [16␣,17␣-d]-derivatives. Thus,
both 16-DPA 1 and its 21-chloro derivative 2 furnished their
[16␣,17␣-d]-isoxazolines 1(a–h) and 2(a–h), respectively, in
good yield (60–75%) when they were refluxed with different
aliphatic and aromatic aldoximes a–h in ethanol. TLC and
other analytical data confirmed the formation of only one
regioisomer viz., [16,17-d]-isoxazolines in all the cases. In
for the C-16 proton. In the IR spectrum, the band for ␣,␤-
unsaturated carbonyl system appearing at 1675 cm−1 disap-
peared with the appearance of a band at 1700–1710 cm−1
for a normal carbonyl group. It is also pertinent to note
that during the reaction in cases of 16-dehydro-21-chloro-
20-oxopregnane 2, chlorine atom was substituted by hy-
droxyl group under the basic reaction condition to give
the corresponding 21-hydroxy-20-oxo pregnane 2(a–h). The
reaction was also found to be selective as cycloaddition
took place only at the ␣,␤-unsaturated double bond at C-
16 leaving the isolated double bond at C5–C6 unaffected
as had been demonstrated by the substrate 1 as shown in
Scheme 1.
The fast reaction of aldoximes with chloramine-T explains
why the reaction proceeds in presence of olefinic double
bond in spite of the fact that the later are known to react
with chloramine-T [23]. The role of chloramine-T in these
transformations may be chlorination of the aldoxime to a
hydroxamic acid chloride followed by base catalyzed HCl
elimination. It has been reported that chlorination of oxime
to ␣-chloronitroso compounds could be accomplished un-
der a variety of conditions [24] and formation of which is
indicated by a blue colour [25] during the reaction. The
various oximes a–h used in the reaction was prepared as
per literature procedure [26]. The steric factor associated
with the steroid molecules suggests that the product might
be 16␣,17␣-d isoxazolines. Further work on biological ac-
tivity evaluation of these new steroid-fused heterocycles is
in progress and will be communicated in due course of
time.
1
the H NMR spectra of the isoxazolines formed, 16-vinyl
hydrogen peak at 6.4 ppm disappeared with the appearance
of a new methine hydrogen peak in the region 3.5–4.9 ppm
Scheme 1.

496
P. Chowdhury et al. / Steroids 70 (2005) 494–498
1. Experimental
1.1. General methods
crotonaldoxime b as per the general procedure furnished the
product 1b.
Mp: 206–208 ◦C, αD: (−)122◦ (C1, CHCl3). IR (KBr):
1
1730, 1710, 1590, 1445, 1210 cm−1. H NMR (300 MHz,
Melting points were determined with an electro thermal
melting point apparatus and are uncorrected. All the chemi-
cals used were of reagent grade of Aldrich Chemical Co. and
were used without further purification. Chloramine-T trihy-
drate used was purchased from Aldrich Chemical Co. Freshly
distilled dichloromethane (DCM) was used. The progresses
of the reactions were monitored by thin layer chromatogra-
phy using silica gel (E Merck) and the plates were activated
at 100 ◦C before use. Infrared spectra were recorded with a
Perkin-Elmer model 2000 series FT-IR spectrometer for so-
lutions in chloroform. Infrared absorbance is reported in re-
ciprocal centimeters (cm−1). 1H NMR spectra were recorded
on a Bruker DPX (300 MHz) spectrometer with tetra methyl
silane (TMS) as internal standard on the ppm scale (δ). Mul-
tiplicity of the resonance peaks are indicated as singlet (s),
broadsinglet(bs), doublet(d), triplet(t), quartet(q)andmulti-
plet (m). Mass spectrometric analysis was performed by pos-
itive mode electro spray ionization with Bruker Esquire 3000
LC-MS instrument. Specific rotations (αD) were recorded on
a Perkin-Elmer Polarimeter 343 instrument. Elemental anal-
ysis was carried out in Varian CHN Analyzer.
CDCl3): δ = 0.8 (s, 3H, Me), 1.1 (s, 3H, Me), 1.8 (s, 1H, Me
under double bond), 1.9 (s, 3H, OAc), 2.0 (s, 3H, COMe), 3.9
(m, 1H, H-16), 4.5 (m, 1H, H-3), 5.3 (m, 1H, H-6), 5.9 (m,
2H, –CH=CH–) ppm. Mass spectrum (m/z): 439 (M+). Anal.
Calcd. for C27H37O4N: C, 73.80; H, 8.43, N, 3.19; Found:
C, 74.13; H, 8.60; N, 3.32.
1.2.1.3. 3β-Acetoxy-20-oxo-3ꢀ-(4-chloro benzo) isoxazolino
[16,17-d] pregna-5-ene (1c). The reaction of 16-DPA 1 with
4-chloro benzaldoxime c as per the general procedure fur-
nished the product 1c.
Mp: 114–116 ◦C; αD: (−)111◦ (C1, CHCl3). IR (KBr):
1
1730, 1710, 1590, 1450, 1205 cm−1. H NMR (300 MHz,
CDCl3): δ = 0.8 (s, 3H, Me), 1.0 (s, 3H, Me), 1.9 (s, 3H, OAc),
2.2 (s, 3H, COMe), 4.1–4.3 (m, 2H, H-3 and H-16), 5.1 (m,
1H, H-6), 7.1–7.4 (m, 4H, Ph) ppm. Mass spectrum (m/z):
509 (M+), 511 (M++2). Anal. Calcd. for C30H36O4NCl(%):
C, 70.73; H, 7.07; N, 2.75; Found: C, 70.84; H, 7.20; N, 2.93.
1.2.1.4. 3β-Acetoxy-20-oxo-3ꢀ-(2-phenyl ethylene) isoxa-
zolino [16,17-d] pregna-5-ene (1d). The reaction of 16-DPA
1 with cinnalmaldoxime d as per the general procedure fur-
nished the product 1d.
1.2. Synthesis of steroidal [16,17-d] isoxazolines 1(a–h)
and 2(a–h)
Mp: 225–228 ◦C, αD: (−)102◦ (C1, CHCl3). IR (KBr):
1730, 1710, 1588, 1400, 1210 cm−1. H NMR (300 MHz,
1
1.2.1. General procedure
CDCl3): δ = 0.9 (s, 3H, Me), 1.0 (s, 3H, Me), 1.9 (s, 3H,
OAc), 2.1 (s, 3H, COMe), 4.24 (m, 2H, H-3 and H-16), 5.3
(m, 1H, H-6), 6.3 (m, 2H, –CH=CH–Ph), 7.1–7.4 (m, 5H,
Ph) ppm. Mass spectrum (m/z): 501 (M+). Anal. Calcd. for
C32H39O4N: C, 76.65; H, 7.78; N, 2.79; Found: C, 76.79; H,
7.87, N, 2.95.
To a solution of a substrate (1.5 m mol) in 25 ml of EtOH,
was added 2.0 m mol of aldoxime followed by chloramines-T
(1.7 m mol). The mixture was heated to reflux with stirring
for 3 h. The reaction was filtered and the filtrate was poured
into cold water. The reaction mixture was then extracted with
CH2Cl2 (2 × 100 ml) and the organic extract after drying over
anhydrous Na2SO4was evaporated under reduced pressure
to furnish a residue. The residue on purification by prepara-
tive TLC (ethyl acetate:petroleum ether: 12:1) and finally on
crystallization from ethanol furnished the desired isoxazoline
derivatives 1(a–h) and 2(a–h).
1.2.1.5. 3β-Acetoxy-20-oxo-3ꢀ-(4-methoxy benzo) isoxa-
zolino [16,17-d] pregna-5-ene (1e). The reaction of 16-DPA
1 with p-anisaldoxime e as per the general procedure fur-
nished the product 1e.
Mp: 119–121 ◦C, αD: (−)116◦ (C1, CHCl3). IR (KBr):
1
1734, 1710, 1587, 1443, 1210 cm−1. H NMR (300 MHz,
1.2.1.1. 3β-Acetoxy-20-oxo-3ꢀ-(Benzo) isoxazolino [16,17-
d] pregna-5-ene (1a). The reaction of 16-DPA 1 with ben-
zaldoxime a according as per the general procedure which
furnished the product 1a.
CDCl3): δ = 0.9 (s, 3H, Me), 1.1 (s, 3H, Me), 1.9 (s, 3H, OAc),
2.1 (s, 3H, COMe), 3.4 (s, 3H, OMe), 4.3 (m, 2H, H-3 and
H-16), 5.2 (m, 1H, H-6), 7.1–7.4 (m, 4H, Ph) ppm. Mass
spectrum (m/z): 505 (M+). Anal. Calcd. for C31H39O5N:
C, 73.66; H, 7.72; N, 2.77; Found: C, 73.51; H, 7.90,
N, 2.82.
Mp: 196–198 ◦C, αD: (−)124◦ (C1, CHCl3). IR (KBr):
ν = 1735, 1710, 1588, 1450, 1200 cm−1. 1H NMR (300 MHz,
CDCl3): δ = 0.9 (s, 3H, Me), 1.0 (s, 3H, Me), 1.9 (s, 3H, OAc),
2.2 (s, 3H, COMe), 4.26 (m, 2H, H-3 and H-16), 5.2 (m, 1H,
H-6), 7.1–7.4 (m, 5H, Ph) ppm. Mass spectrum (m/z): 475
(M+). Anal. Calcd. for C30H37O4N: C, 75.79; H, 7.79; N,
2.95; Found: C, 75.48; H, 7.60, N, 3.13.
1.2.1.6. 3β-Acetoxy-20-oxo-3ꢀ-(4-methyl benzo) isoxazolino
[16,17-d] pregna-5-ene (1f). The reaction of 16-DPA 1 with
p-tolualdoxime f as per the general procedure furnished the
product 1f.
Mp: 121–123 ◦C, αD: (−)114◦ (C1, CHCl3). IR (KBr):
1.2.1.2. 3β-Acetoxy-20-oxo-3ꢀ-(prop-1-ene)
[16,17-d] pregna-5-ene (1b). The reaction of 16-DPA 1 with
isoxazolino
1735, 1710, 1589, 1445, 1200 cm−1. H NMR (300 MHz,
1
CDCl3): δ = 0.8 (s, 3H, Me), 1.1 (s, 3H, Me), 1.9 (s, 3H,

P. Chowdhury et al. / Steroids 70 (2005) 494–498
497
spectrum (m/z): 457 (M+). Anal. Calcd. for C27H39O5N:
C, 70.90; H, 8.53, N, 3.06; Found: C, 71.03; H, 8.66; N,
3.19.
OAc), 2.2 (bs, 6H, Me and COMe), 4.25 (m, 2H, H-3 and
H-16), 5.3 (m, 1H, H-6), 7.1–7.5 (m, 4H, Ph) ppm. Mass
spectrum (m/z): 489 (M+). Anal. Calcd. for C31H39O4N:
C, 76.07; H, 7.98; N, 2.86; Found: C, 76.19; H, 7.84,
N, 2.93.
1.2.1.11. 21-Hydroxy-3β-acetoxy-20-oxo-3ꢀ- (p-chlorobe-
nzo) isoxazolino [16,17-d] pregna-5-ene (2c). The reaction
of 21-chloro-16-dehydro-5, 6-dihydro pregnenolone acetate
2 with p-chlorobenzaldoxime c as per the general procedure
furnished the product 2c.
1.2.1.7. 3β-Acetoxy-20-oxo-3ꢀ-(4-nitro benzo) isoxazolino
[16,17-d] pregna-5-ene (1g). The reaction of 16-DPA 1 with
p-nitrobenzaldoxime g as per the general procedure furnished
the product 1g.
Mp: 139–141 ◦C; αD: (+)5◦ (C1, alc). IR (KBr): 3300,
Mp: 109–111 ◦C, αD: (−)108◦ (C1, CHCl3). IR (KBr):
1
1736, 1710, 1590, 1450, 1205 cm−1. H NMR (300 MHz,
1
1730, 1710, 1590, 1528, 1450, 1347, 1245, 855 cm−1. H
CDCl3): δ = 0.8 (s, 3H, Me), 1.0 (s, 3H, Me), 1.9 (s, 3H, OAc),
2.2 (s, 3H, COMe), 3.2 (d, J = 19 Hz, H-21), 3.6 (d, J = 19Hz,
H-21), 4.5 (m, 1H, H-3), 4.9 (m, 1H, H-16), 7.1–7.4 (m, 4H,
Ph) ppm. Mass spectrum (m/z): 527 (M+), 529 (M++2). Anal.
Calcd. for C30H38O5NCl(%): C, 68.31; H, 7.21; N, 2.66;
Found: C, 68.54; H, 7.39; N, 2.51.
NMR (300 MHz, CDCl3): δ = 0.9 (s, 3H, Me), 1.0 (s, 3H,
Me), 1.9 (s, 3H, OAc), 2.2 (s, 3H, COMe), 4.31 (m, 2H, H-
3 and H-16), 5.3 (m, 1H, H-6), 7.1–7.4 (m, 4H, Ph) ppm.
Mass spectrum (m/z): 520 (M+), 521 (M++1). Anal. Calcd.
for C30H36O6N2: C, 69.23; H, 6.92; N, 5.38; Found: C, 69.08;
H, 6.85, N, 5.23.
1.2.1.12. 21-Hydroxy-3β-acetoxy-20-oxo-3ꢀ- (phenyl ethy-
lene) isoxazolino [16,17-d] pregna-5-ene (2d). The reaction
of 21-chloro-16-dehydro-5, 6-dihydro pregnenolone acetate
2 with cinnamaldoxime d as per the general procedure fur-
nished the product 2d.
1.2.1.8. 3β-Acetoxy-20-oxo-3ꢀ-(n-heptyl) isoxazolino [16,
17-d] pregna-5-ene (1h). The reaction of 16-DPA 1 with
octanaldoxime h as per the general procedure furnished the
product 1h.
Mp: 224–226 ◦C, αD: (−)118◦ (C1, CHCl3). IR (KBr):
Mp: 248–250 ◦C, αD: (+)7◦ (C1, alc). IR (KBr): 3350,
1730, 1710, 1593, 1443, 121 cm−1 1H NMR (300 MHz,
.
1
1730, 1710, 1588, 1400, 1210 cm−1. H NMR (300 MHz,
CDCl3): δ = 0.9 (s, 3H, Me), 1.0 (s, 3H, Me), 1.9 (s, 3H,
OAc), 2.1 (s, 3H, COMe), 3.4 (m, 1H, H-16), 4.3 (m, 1H,
H-3), 5.3 (m, 1H, H-6) ppm. Mass spectrum (m/z): 497 (M+).
Anal. Calcd. for C31H47O4N: C, 74.85; H, 9.46; N, 2.82;
Found: C, 74.96; H, 9.54, N, 2.89.
CDCl3): δ = 0.9 (s, 3H, Me), 1.0 (s, 3H, Me), 1.9 (s, 3H,
OAc), 2.1 (s, 3H, COMe), 3.3 (d, J = 19 Hz, H-21), 3.6 (d,
J = 19Hz, H-21), 4.4 (m, 1H, H-3), 4.8 (m, 1H, H-16), 6.3
(m, 2H, –CH=CH–Ph), 7.1–7.4 (m, 5H, Ph) ppm. Mass
spectrum (m/z): 519 (M+). Anal. Calcd. for C32H41O5N:
C, 73.99; H, 7.90; N, 2.70; Found: C, 74.12; H, 7.77, N,
2.92.
1.2.1.9. 21-Hydroxy-3β-acetoxy-20-oxo-3ꢀ- (benzo) isoxa-
zolino [16,17-d] pregna-5-ene (2a). The reaction of 21-
chloro-16-dehydro-5, 6-dihydro pregnenolone acetate 2 with
benzaldoxime a as per the general procedure furnished the
product 2a.
1.2.1.13. 21-Hydroxy-3β-acetoxy-20-oxo-3ꢀ- (4-methoxyb-
enzo) isoxazolino [16,17-d] pregna-5-ene (2e). The reaction
of 21-chloro-16-dehydro-5, 6-dihydro pregnenolone acetate
2 with p-anisaldoxime e as per the general procedure fur-
nished the product 2e.
Mp: 212–214 ◦C, αD: (+)12◦ (C1, alc). IR (KBr):
1
3300, 1735, 1710, 1590, 1444, 1210, 800 cm−1. H NMR
Mp: 144–146 ◦C, αD: (+)3◦ (C1, alc). IR (KBr): 3305,
(300 MHz, CDCl3): δ = 0.9 (s, 3H, Me), 1.1 (s, 3H, Me), 1.9
(s, 3H, OAc), 2.2 (s, 3H, COMe), 3.4 (d, J = 19 Hz, H-21),
3.7 (d, J = 19 Hz, H-21), 4.4 (m, 1H, H-3), 4.9 (m, 1H, H-16),
7.1–7.4 (m, 5H, Ph) ppm. Mass spectrum (m/z): 493 (M+).
Anal. Cacld. for C30H39O5N: C, 73.02; H, 7.91; N, 2.84;
Found: C, 73.29; H, 7.61, N, 3.05.
1
1734, 1710, 1587, 1443, 1210 cm−1. H NMR (300 MHz,
CDCl3): δ = 0.9 (s, 3H, Me), 1.1 (s, 3H, Me), 1.9 (s, 3H,
OAc), 2.1 (s, 3H, COMe), 3.2–3.4 (m, 4H, H-21 and OMe),
3.6 (d, J = 19 Hz, H-21), 4.5 (m, 1H, H-3), 4.8 (m, 1H, H-16),
7.1–7.4 (m, 4H, Ph) ppm. Mass spectrum (m/z): 523 (M+).
Anal. Calcd. for C31H41O6N: C, 71.13; H, 7.84; N, 2.68;
Found: C, 71.34; H, 7.95, N, 2.75.
1.2.1.10. 21-Hydroxy-3β-acetoxy-20-oxo-3ꢀ- (prop-1-ene)
isoxazolino [16,17-d] pregna-5-ene (2b). The reaction of 21-
chloro-16-dehydro-5, 6-dihydro pregnenolone acetate 2 with
crotonaldoxime b as per the general procedure furnished the
product 2b.
1.2.1.14. 21-Hydroxy-3β-acetoxy-20-oxo-3ꢀ- (p-methylbe-
nzo) isoxazolino [16,17-d] pregna-5-ene (2f). The reaction
of 21-chloro-16-dehydro-5, 6-dihydro pregnenolone acetate
2 with p-tolualdoxime f as per the general procedure fur-
nished the product 2f.
Mp: 227–229 ◦C, αD: (+)11◦ (C1, alc). IR (KBr): 3303,
1
1734, 1710, 1590, 1445, 1210 cm−1. H NMR (300 MHz,
CDCl3): δ = 0.8 (s, 3H, Me), 1.1 (s, 3H, Me), 1.8 (s, 1H, Me
under double bond), 1.9 (s, 3H, OAc), 2.0 (s, 3H, COMe),
3.4 (d, J = 19 Hz, H-21), 3.7 (d, J = 19Hz, H-21), 3.9 (m, 1H,
H-16), 4.5 (m, 1H, H-3), 5.9 (m, 2H, –CH=CH–) ppm. Mass
Mp: 142–144 ◦C, αD: (+)8◦ (C1, alc). IR (KBr): 3300,
1
1735, 1710, 1589, 1445, 1200 cm−1. H NMR (300 MHz,
CDCl3): δ = 0.8 (s, 3H, Me), 1.1 (s, 3H, Me), 1.9 (s, 3H,
OAc), 2.2 (bs, 6H, Me and COMe), 3.4 (d, J = 19 Hz,

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P. Chowdhury et al. / Steroids 70 (2005) 494–498
H-21), 3.7 (d, J = 19Hz, H-21), 4.4 (m, 1H, H-3), 4.9
(m, 1H, H-16), 7.1–7.5 (m, 4H, Ph) ppm. Mass spec-
trum (m/z): 507 (M+). Anal. Calcd. for C31H41O5N: C,
73.37; H, 8.09; N, 2.76; Found: C, 73.54; H, 8.22, N,
2.85.
References
[1] (a) Padwa A. 1,3-Dipolar cycloaddition chemistry, vol. 2. New York:
John Wiley & Sons; 1984. p. 83;
(b) Torsell KGB. Nitrile oxides, nitrones and nitronates in organic
synthesis. Weinheim: VCH; 1988.
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Kennewell P. Tetrahedron 2000;56:10087.
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(b) Curran DP, Kim BH. Synthesis 1986:312.
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X, et al. J Med Chem 1982;25:1492.
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1987;28:1097;
1.2.1.15. 21-Hydroxy-3β-acetoxy-20-oxo-3ꢀ- (p-nitrobenzo)
isoxazolino [16,17-d] pregna-5-ene (2g). The reaction of 21-
chloro-16-dehydro-5, 6-dihydro pregnenolone acetate 2 with
p-nitrobenzaldoxime g as per the general procedure furnished
the product 2g.
Mp: 133–136 ◦C, αD: (+) 2.5◦ (C1, alc). IR (KBr): 3313,
1
1730, 1710, 1590, 1528, 1450, 1347, 1245, 855 cm−1. H
NMR (300 MHz, CDCl3): δ = 0.9 (s, 3H, Me), 1.0 (s, 3H,
Me), 1.9 (s, 3H, OAc), 2.2 (s, 3H, COMe), 3.3 (d, J = 19 Hz,
H-21), 3.7 (d, J = 19Hz, H-21), 4.5 (m, 1H, H-3), 4.9 (m,
1H, H-16), 7.1–7.4 (m, 4H, Ph) ppm. Mass spectrum (m/z):
538 (M+), 539 (M++1). Anal. Calcd. for C30H38O7N2:
C, 66.91; H, 7.06; N, 5.20; Found: C, 67.09; H, 6.91,
N, 5.38.
(b) Corbett DF. J Chem Soc Perkin Trans I 1986;421.
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1.2.1.16. 21-Hydroxy-3β-acetoxy-20-oxo-3ꢀ- (octanal) isox-
azolino [16,17-d] pregna-5-ene (2h). The reaction of 21-
chloro-16-dehydro-5, 6-dihydro pregnenolone acetate 2 with
octanaldoxime h as per the general procedure furnished the
product 2h.
(b) Lobry CA. Chem Ber 1886;19:1370.
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[17] Chowdhury PK, Bordoloi MJ, Baruah NC, Sharma HP, Goswami
PK, Sharma RP, et al. US Patent No. 5,808,117. Chem Abs 1998;29:
230884e.
Mp: 249–251 ◦C, αD: (+)9◦ (C1, alc). IR (KBr): 3310,
1730, 1710, 1593, 1443, 1210 cm−1. H NMR (300 MHz,
1
CDCl3): δ = 0.9 (s, 3H, Me), 1.0 (s, 3H, Me), 1.9 (s, 3H,
OAc), 2.1 (s, 3H, COMe), 3.3–3.5 (m, 2H, H-21 and H-
16), 3.6 (d, J = 19Hz, H-21), 4.5 (m, 1H, H-3) ppm. Mass
spectrum (m/z): 515 (M+). Anal. Calcd. for C31H49O5N:
C, 72.23; H, 9.51; N, 2.72; Found: C, 72.07; H, 9.34, N,
2.59.
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Chem Soc Perkin Trans I 1993:1433.
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Longman; 1946.
Acknowledgement
One of the authors (AMD) thanks CSIR, New Delhi for
awarding a Research Associateship.