6
2
steroids 7 2 ( 2 0 0 7 ) 60–63
2
.2.
The typical deprotective procedure
123.8; 121.4; 119.0 118.7; 118.5; 118.2; 107.2; 53.1; 44.4; 42.0;
1.9; 37.4; 34.6; 34.5; 34.0; 32.9; 31.2; 30.3; 27.7; 27.0; MS (m/z,
4
ꢀ
2
.2.1. Deprotection of 3 -methylspiro[androsta-1,4-dien-
%): 430 (M + 1, 86.02), 415 (M-CH3, 41.65), 43 (Ac-, base): ꢀ(KBr)
ꢀ
ꢀ
−1
3
,2 (3 H)benzothiazol]-17-one (1)
(cm ): 1660 (C O), 1474 (arom), 1299 (Ar-N), 738 (arom); opti-
2
0
◦
◦
pTSA (201 mg, 1.06 mmol) and ethyl vinyl ether (763 mg,
cal rotation: [˛]D = +188.4 (CHCl3, 0.01 g/mL); mp: 203–206 C
ꢀ
1
0.6 mmol) were added to a solution of 3 -methylspiro-
(recrystallyzed from ethyl acetate).
ꢀ
ꢀ
[
1
androsta-1,4-dien-3,2 (3 H)benzothiazol]-17-one (1) (430 mg,
.06 mmol) in 10 mL THF. The mixture was stirred at room
2.3.3. 17˛-Acetoxy-17ˇ-cyanoandrosta-1,4,9(11)-trien-
3-one (7)
temperature for 15 min, then washed with aqueous Na2CO3,
extracted with chloroform (30 mL ×3), and dried over Na2SO4.
After filtration, removal of the solvent gave a yellow oil.
This oil was purified by silica column chromatography by
elution with ethyl acetate/petroleum (1:100) to afford 2-(1-
ethoxyethylthio)-N-methylbenzeneamine (10) (152 mg) in 68%
yield, and by elution with ethyl acetate/petroleum (1:1) to
afford androsta-1,4-dien-3,17-dione (280 mg) in 93% yield.
1
H NMR (CDCl3, 300 MHz) ı: 1.06 (3H, s, 18-CH3), 1.16–2.69 (12H,
m, steroidal skeleton saturated H), 1.44 (3H, s, 19-CH3), 2.08
(3H, s, –C(O)CH3), 5.62 (1H, d, J = 5.7 Hz, 11-H), 6.09 (1H, s, 4-H),
6.30 (1H, dd, J1 = 1.3 Hz, J2 = 10.2 Hz, 2-H), 7.21 (1H, d, J = 10.2 Hz,
+
+
1-H); MS (m/z, %): 352 (M + 1, 6.76), 351 (M , 6.16), 43 (AcO,
◦
base); mp: 204–206 C (recrystallyzed from methanol).
2
.3.4. 17-Cyanoandrosta-1,4,9(11),16-tetraen-3-one (8)
ꢀ
1
2
3
.2.2. Deprotection of 3 -methylspiro[androsta-1,4-dien-
H NMR (CDCl3, 400 MHz) ı: 0.85–2.71 (10H, m, steroidal skele-
ton saturated H), 0.95 (3H, s, 18-CH3), 1.44 (3H, s, 19-CH3),
5.60 (1H, s, 11-H), 6.09 (1H, s, 4-H), 6.30 (1H, dd, J1 = 1.8 Hz,
J2 = 10.3 Hz, 2-H), 6.66 (1H, s, 16-H), 7.21 (1H, d, J = 10.3 Hz, 1-H);
MS (m/z, %): 291(M , 29.14), 149 (base); mp: 138–140 C (recrys-
tallyzed from ethyl acetate).
ꢀ
ꢀ
,2 (3 H)benzothiazol]-9(11),16-dien-17-nitrile (4)
pTSA (201 mg, 1.06 mmol) and ethyl vinyl ether (763 mg,
0.6 mmol) were added to a solution of 3 -methylspiro[andro-
sta-1,4-dien-3,2 (3 H)benzothiazol]-9(11),16-dien-17-nitrile (4)
437 mg, 1.06 mmol) in 10 mL THF. The mixture was stirred
ꢀ
1
ꢀ
ꢀ
+
◦
(
at room temperature for 15 min, then washed with aqueous
Na2CO3, extracted with chloroform (30 mL ×3), and dried over
Na2SO4. After filtration, removal of the solvent gave a yellow
oil. This oil was purified by silica column chromatography
by elution with ethyl acetate/petroleum (1:100) to afford 2-
2.3.5. 2-(1-Ethoxyethylthio)-N-methylbenzeneamine (10)
H NMR (CDCl3, 400 MHz) ı: 1.21 (3H, t, J = 7.1 Hz, –OCH2CH3),
1
1.44 (3H, d, J = 6.3 Hz, S-CH(CH3)-O), 2.87 (3H, s, NCH3), 3.47
(1H, m, –OCH2CH3), 3.93 (1H, m, –OCH2CH3), 4.74 (1H, q,
J1 = 6.3 Hz, J2 = 12.4 Hz, S-CH(CH3)-O), 5.21 (1H, br, NH), 6.61 (2H,
q, J1 = 7.2 Hz, J2 = 7.4 Hz, arom-H), 7.24 (1H, t, J = 7.3 Hz, arom-
H), 7.35 (1H, d, J = 7.6 Hz, arom-H); 13C NMR (CDCl3, 400 MHz) ı:
14.943 (-OCH2CH3), 22.517 (S-CH(CH3)-O), 30.432 (NCH3), 64.202
(
6
1-ethoxyethylthio)-N-methylbenzeneamine (10) (138 mg) in
2% yield, and by elution with ethyl acetate/petroleum
(
1:1) to afford 17-cyanoandrosta-1,4,9(11),16-tetraen-3-one (8)
(
271 mg) in 88% yield.
(
-OCH2CH3), 85.131 (S-CH(CH3)-O), 109.457 (arom-c), 114.601
2
.3.
Analytical and spectroscopic data of compounds
(arom-c), 116.337 (arom-c), 130.431 (arom-c), 137.493 (arom-c),
+
+
1
51.101 (arom-c); MS (m/z, %): 211 (M , 2.86), 139 (M -CH2-
ꢀ
−1
2
.3.1. 3 -Methylspiro[androsta-1,4-dien-
CH-OCH2CH3, 40.11), 43 (CH3CH2O-, base); ꢀ(KBr) (cm ): 3388
(Ar-NH); optical rotation: [˛] 2D 0 = +0.07 (CHCl3, 0.027 g/mL). Col-
orless liquid.
ꢀ ꢀ
◦
3
,2 (3 H)benzothiazol]-9(11), 16-dien-17-nitrile (4)
1
H NMR (CDCl3, 400 MHz) ı: 0.90 (3H, s, 18-CH3), 0.96–2.61
(
10H, m, steroidal skeleton saturated H), 1.30 (3H, s, 19-CH3),
The proton NMR, IR and MS data of androsta-1,4,9(11)-
trien-3,17-dione (6) and pregna-1,4,9(11), 16-tetraen-3,20-
dione (9) agreed well with the literature value. Androsta-
2
4
6
.56 (3H, s, –N(CH3)), 5.52 (1H, d, J = 5.5 Hz, 11-H), 5.73 (1H, s,
-H), 6.02–6.13 (2H, m, arom-H), 6.29 (1H, t, J = 6.9 Hz, 2-H),
.64–6.68 (2H, m, 1-H and 16-H), 6.98 (2H, m, arom-H); 13C
◦
1,4,9(11)-trien-3,17-dione (6), mp: 166–167 C (Lit. [9], mp:
◦
NMR (CDCl3, 400 MHz) ı: 147.2; 146.7; 145.8; 145.2; 136.4; 125.7;
1
4
167–169 C). Pregna-1,4,9(11),16-tetraen-3,20-dione (9), mp:
◦
◦
24.7; 124.2; 121.5; 119.0; 118.7; 117.6; 117.2; 115.8; 107.4; 52.6;
6.8; 42.1; 42.0; 36.4; 34.8; 34.7; 33.9; 33.5; 31.1; 30.3; 27.7; MS
206–208 C (Lit. [10], mp: 204–208 C).
+
+
−1
(cm ): 2215
KBr)
(
(
[
m/z, %): 412 (M , base), 397 (M -CH3, 60.72); ꢀ
(
CN), 1471 (arom), 1295 (Ar-N), 740 (arom); optical rotation:
3.
Results and discussion
2
0
◦
◦
˛] = +187.0 (CHCl3, 0.01 g/mL); mp: 157–160 C (recrystal-
D
lyzed from methanol).
We applied this method on the 3-protected substrates (1–5)
and got the corresponding 3-deprotected products ADD, (6–9)
in excellent yields. As experiments show, this deprotective
method has a high chemo-selectivity, and the cyano, ester
groups and double bond in substrates are not attacked.
In our method, the alkyl vinyl ethers could be ethyl vinyl
ether, butyl vinyl ether and 3,4-dihydro-2H-pyran. However,
the reaction rate with ethyl vinyl ether and butyl vinyl ether as
deprotective agents is quite similar and fast (about 15–30 min).
But when 2H-pyran was used as the deprotective agent, the
reaction rate was much slower (the completion of reaction
could be lasted up to 5 h). The protic acids using in our method
ꢀ
2
3
1
.3.2. 3 -Methylspiro[pregna-1,4-dien-
ꢀ ꢀ
,2 (3 H)benzothiazol]-9(11),16-dien-20-one (5)
H NMR (CDCl3, 400 MHz) ı: 0.86 (3H, s, 18-CH3), 0.88–2.61 (10H,
m, steroidal skeleton saturated H), 1.30 (3H, s, 19-CH3), 2.28
(
3H, s, 21-CH3), 2.56 (3H, s, –N(CH3)), 5.49 (1H, d, J = 5.9 Hz, 11-
H), 5.71 (1H, s, 4-H), 6.02 (1H, m, arom-H), 6.12 (1H, t, J1 = 10.0 Hz,
J2 = 12.6 Hz, arom-H), 6.28 (1H, t, J1 = 7.5 Hz, J2 = 7.9 Hz, 2-H), 6.65
(
1H, t, J = 7.5 Hz, 1-H), 6.72 (1H, d, J = 3.3 Hz, 16-H), 6.97 (2H,
m, J1 = 4.4 Hz, J2 = 7.5 Hz, arom-H); 13C NMR (CDCl3, 400 MHz)
ı: 196.5 (20-C); 153.6; 146.4; 144.9; 144.0; 136.8; 125.6; 124.7;