500
P. Chowdhury et al. / Steroids 76 (2011) 497–501
Yield: 400 mg (88%); M.P: 181 ◦C; IR (cm−1): 3300, 1350, 1250;
1H NMR (DMSO-d6): 0.9 (s, 3H, Me), ı 1.0 (s, 3H, Me), 0.9–2.1 (m,
22H, –CH and –CH2), 3.5 (m, 3H, H-3 and H-21), 3.8–4.1 (m, 2H,
3- and 21-OH), 5.3 (m, 1H, H-21); 13C NMR: ı 34.2(C-1), 35.1(C-
2), 67.6 (C-3), 39.5(C-4), 41.9(C-5), 28.1(C-6), 32.0(C-7), 29.0(C-8),
46.2(C-9),35.4(C-10), 20.9(C-11), 39.5(C-12), 40.5(C-13), 55.4(C-
14), 32.7(C-15), 36.6(C-16), 152.3(C-17), 16.7(C-18), 15.2(C-19),
114.9(C-20), 64.6(C-21); mass spectrum (m z−1): 318 (M+), 300,
283, 253; Anal. Calcd. for C21 H34 O2: C,79.25; H,10.69; found:
C,79.18; H,10.03.
ether and ethyl acetate as the eluent to furnish 3-acetoxy-5␣-
pregnan-20-one 3 in pure form.
Yield: 1.9 g (95%); Mp: 172 ◦C; IR (cm−1): 1735, 1700, 1450,
1200; 1H NMR (CDCl3): 0.9 (s, 3H, Me), ı 1.0 (s, 3H, Me), 0.9–1.9
(m, 23H, –CH and –CH2), 2.0 (s, 3H, OAc), 2.2 (s, 3H, COMe), 4.3
(m, 1H, H-3); 13C NMR: ı 34.2(C-1), 35.1(C-2), 78.6(C-3), 39.5(C-4),
41.9(C-5), 28.1(C-6), 32.0(C-7), 29.0(C-8), 46.2(C-9), 35.4(C-
10), 20.9(C-11), 39.5(C-12), 40.5(C-13), 55.4(C-14), 34.7(C-15),
22.9(C-16), 69.5(C-17), 16.7(C-18), 15.2(C-19), 172.9(C–OCOCH3),
212.5(C-20), 21.3(C-21); mass spectrum (m z−1): 360 (M+), 318,
300, 298, 257; Anal. Calcd. for C23 H36 O3: C,76.66; H, 8.91; found:
C,76.41; H,9.03.
1.2.4. 3ˇ, 21-Diacetoxy-pregn-17(20)-ene 7
To a solution of 500 mg of pregn-17(20)-ene-3, 21-diol 6 in
20 ml of glacial AcOH was added 50 mg of CAN. The reaction mix-
ture was heated in the range 50–60 ◦C and was monitored on
TLC. After completion of the reaction, the reaction mixture was
poured into cold water and was extracted with petroleum ether.
The organic extract was dried over anhydrous Na2SO4 and was
distilled under reduced pressure to get a residue which was puri-
fied by preparative TLC (EtOAc:petroleum ether: 1:10) to furnish
3,21-diacetoxy-pregn-17(20)-ene 7 in pure form as a solid.
Mp: 154 ◦C; yield: 450 mg (75%); IR (cm−1): 1725 (broad), 1350,
1250; 1H NMR (CDCl3): ı 0.9 (s, 3H, Me), 1.1 (s, 3H, Me), 0.8–1.9
(m, 22H, –CH and –CH2), 2.0 (bs, 6H, OAc), 4.3–4.5 (m, 3H, H-3 and
H-21), 5.3 (m, 1H, H-20); 13C NMR: ı 34.2(C-1), 35.1(C-2), 72.4 (C-
3), 39.5(C-4), 41.9(C-5), 28.1(C-6),32.0(C-7), 29.0(C-8), 46.2(C-9),
35.4(C-10), 20.9(C-11), 39.5(C-12), 40.5(C-13), 53.6(C-14), 32.7(C-
15), 36.6(C-16), 152.3(C-17), 16.7(C-18), 15.2(C-19), 114.9(C-20),
71.7(C-21), 173.1(C-OCOCH3); mass spectrum (m z−1): 402 (M+),
360, 342, 284; Anal. Calcd. for C25 H38 O4: C,74.63; H,9.45; found:
C,74.51; H,9.39.
1.2.1. 17˛,21-Dichloro-3ˇ-acetoxy-5˛-pregnan-20-one 4
To a solution of 200 mg of 3-acetoxy-5␣-pregnan-20-one 3 in
10 ml of glacial acetic acid was added excess of MnO2 (170 mg) and
then 1 ml of AcCl or 4 ml of TMSCl. The reaction mixture was kept
overnight at room temperature. Then, the reaction mixture was
poured into cold water and extracted with petroleum ether. The
organic extract after drying over anhydrous sodium sulphate was
evaporated under reduced pressure to furnish a residue which was
purified by preparative TLC (EtOAc:petroleum ether: 1:12,v/v) to
get 17␣,21-dichloro-3-acetoxy-5␣-pregnan-20-one 4 as solid.
Yield: 190 mg (81%); MP: 160 ◦C; IR (cm−1): 1730, 1710, 1445,
1200; 1H NMR (CDCl3): 0.9 (s, 3H, Me), ı 1.0 (s, 3H, Me), 0.9–2.0 (m,
22H, –CH and –CH2), 2.1 (s, 3H, OAc), 4.2 (d, J = 1.5 Hz, 2H, H-21),
4.5 (m, 1H, H-3); 13C NMR: ı 34.2(C-1), 35.1(C-2), 78.6(C-3), 39.5(C-
4), 41.9(C-5), 28.1(C-6), 32.0(C-7), 29.0(C-8), 46.2(C-9), 35.4(C-10),
20.9(C-11), 39.5(C-12), 40.5(C-13), 55.4(C-14), 34.7(C-15), 22.9(C-
16), 89.7 (C-17), 16.7(C-18), 15.2(C-19), 171.2(C-OCOCH3), 192.6
(C-20), 50.2(C-21); mass spectrum (m z−1): 428 (M+), 430 (M++2),
432 (M++4), 392, 368, 332; Anal. Calcd. for C23 H34 O3Cl2: C,64.49;
H,7.94; found: C,64.46; H,7.89.
1.2.5. 3ˇ, 21-Diacetoxy-17˛, 20˛-epoxy-5˛-pregnane 8a and
3ˇ, 21-diacetoxy-17ˇ, 20ˇ-epoxy-5˛-pregnane 8b
1.2.2. Pregn-17(20)-ene-3ˇ-ol-21-oic acid methyl ester 5
Two-hundred milligrams of the compound 17␣,21-dichloro-
3-acetoxy-5␣-pregnan-20-one 4 was allowed to stir with 3% KOH
in MeOH–H2O (85:15) at room temperature for a period of 3 h.
The reaction was monitored on TLC. When TLC indicated that the
starting material had all been used up, the reaction mixture was
poured into cold water and was acidified with citric acid. It was
then extracted with CH2Cl2 (3 × 150 ml). The organic extract was
dried over anhydrous Na2SO4 and was evaporated under reduced
pressure. The residue so obtained was purified by preparative TLC
(EtOAc:petroleum ether: 1:5, v/v) to get the pure pregn-17(20)-
ene-3-ol-21-oic acid methyl ester 5 in the form of a gum.
To a solution of 500 mg of 3,21-diacetoxy-pregn-17(20)-ene 7
in 20 ml of chloroform added 150 mg of m-CPBA. The reaction mix-
ture was kept overnight at room temperature. On the following
day, TLC indicated the formation of two polar products. The reac-
tion mixture was then poured into cold water and was extracted
with dichloromethane. The organic extract was washed first with
an aqueous solution of sodium meta-bisulphite and then with a 5%
NaOH aqueous solution. Finally the organic extract after drying over
anhydrous Na2SO4 was distilled under reduced pressure to furnish
a residue which was purified by preparative TLC (EtOAc:petroleum
ether: 1:1) to give 8a as the major and 8b as the minor products.
Yield: 8a: 320 mg (62%); IR (cm−1): 1730 (broad), 1350, 1260;
1H NMR (CDCl3): ı 0.9 (s, 3H, Me), 1.0 (s, 3H, Me), 0.91-1.9 (m, 22H,
–CH and –CH2), 2.1 (bs, 6H, OAc), 3.1 (m, 1H, H-20), 4.3–4.5 (m, 3H,
H-3 and H-21)); 13C NMR (CDCl3): ı 34.2(C-1), 35.1(C-2), 72.4 (C-
3), 39.5(C-4), 41.9(C-5), 28.1(C-6), 32.0(C-7), 29.0(C-8), 46.2(C-9),
35.4(C-10), 20.9(C-11), 39.5(C-12), 40.5(C-13), 53.6(C-14), 32.7(C-
15), 36.6(C-16), 74.3(C-17), 16.7(C-18), 15.2(C-19), 57.2(C-20),
72.4(C-21), 173.1(C–OCOCH3); mass spectrum (m z−1): 418 (M+),
376, 258, 200,184; Anal. Calcd. for C25 H38 O5: C,71.77; H,9.09;
found: C,71.72; H,9.00.
Yield: 120 mg (75%); IR (cm−1): 3400, 1730, 1250; 1H NMR
(CDCl3): ı 0.8 (s, 3H, Me), 1.0 (s, 3H, Me), 0.9–2.1 (m, 23H, –CH and
–CH2), 2.4 (m, 1H, 3-OH), 3.4 (s, 3H, OMe), 3.6 (m, 1H, H-3), 5.3
(s, 1H, H-20); 13C NMR: ı 34.2(C-1), 35.1(C-2), 67.6 (C-3), 39.5(C-
4), 41.9(C-5), 28.1(C-6), 32.0(C-7), 29.0(C-8), 46.2(C-9), 35.4(C-10),
20.9(C-11), 39.5(C-12), 40.5(C-13), 55.4 (C-14), 32.7(C-15), 36.6(C-
16), 164.8 (C-17), 16.7(C-18), 15.2(C-19), 114.8C-20), 167.9(C-21),
52.7(C–OCH3); Mass spectrum (m z−1): 346 (M+), 328, 288, 270;
Anal. Calcd. for C22H34 O3: C,76.30; H,9.83; found: C,76.21; H,9.76.
1.2.3. Pregn-17(20)-ene-3ˇ,21-diol 6
Yield: 8b: 100 mg (20%); IR (cm−1): 1735 (broad), 1340, 1250;
1H NMR (CDCl3): ı 0.9 (s, 3H, Me), 1.0 (s, 3H, Me), 0.9–1.9 (m, 22H,
–CH and –CH2), 2.0 (bs,6H, OAc), 3.3 (m, 1H, H-20), 4.4–4.6 (m, 3H,
H-3 and H-21); 13C NMR (CDCl3): ı34.2(C-1), 35.1(C-2), 72.4 (C-
3), 39.5(C-4), 41.9(C-5), 28.1(C-6), 32.0(C-7), 29.0(C-8), 46.2(C-9),
35.4(C-10), 20.9(C-11), 39.5(C-12), 40.5(C-13), 53.6(C-14), 32.7(C-
15), 36.6(C-16), 74.3(C-17),16.7(C-18), 15.2(C-19), 57.2(C-20), 72.4
(C-21), 173.1(C–OCOCH3); mass spectrum (m z−1): 418 (M+), 376,
258, 200,184; Anal. Calcd. for C25 H38 O5: C,71.77; H,9.09; found:
C,71.67; H,8.94.
Five-hundred milligrams of substrate 5 was dissolved in 25 ml of
anhydrous THF. The reaction was allowed to stir at room tempera-
ture and to it was added 300 mg LiAlH4. The mixture was allowed to
stir for 4 h and was monitored on TLC. When TLC indicated comple-
tionofthe reaction, thereactionmixturewas filtered andthe filtrate
was poured into cold water and was extracted with CH2Cl2. The
organic extract after drying over anhydrous Na2SO4 was distilled
under reduced pressure to get a residue. The residue was purified
by preparative TLC, which furnished a solid product pregn-17(20)-
ene-3,21-diol 6.