7
42
S. Deb, K. Wähälä / Steroids 75 (2010) 740–744
Table 2
Synthesis of fatty acid esters of steroids synthesized in IL/MW.
Entry
1
Substrate
Product
Yield (%)a
Estradiol 1
Estradiol dioleate 6
Estradiol dilinoleate 7
Estradioldistearate 8
Estradiol dipalmitate 9
89%
92%
90%
91%
2
3
Dehydroepiandrosterone 10
5␣-androstane-3,17-diol 13
Testosterone 16
5-Androsten-3-ol-17-one oleate 11
-Androsten-3-ol-17-one linoleate 12
85%
92%
5
5␣-Androstane-3,17-diol dioleate 14
␣-Androstane-3,17-diol dilinoleate 15
85%
74%
5
4
4-Androsten-17-ol–3-one oleate 17
-Androsten-17-ol–3-one linoleate 18
83%
79%
4
a
Isolated yields.
ꢀ
ꢀ
8
2
1
2.57 (C-17), 12.29 (C-18), 174.10, 172.78 (C-1 ), 34.81, 34.63 (C-2 ),
2.3.5. 5˛-Androstane-3ˇ,17ˇ-diol dioleate 14
Colorless liquid, Rf in 5:1 n-hexane/EtOAc is 0.64. 1H NMR
ꢀ
ꢀ
ꢀ
ꢀ
5.33, 25.20 (C-3 ), 29.33–29.9 (C-4 –C-7 and C-12-C-15 ), 130.23,
29.95 (C-9 , C-10 ), 22.88 (C-17 ), 14.31 (C-18 ). MS m/z (relative
intensity) 800 M (3), 536 (44), 272 (22), 255 (50), 159 (16), 133 (8).
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(CDCl ) ı: 5.34 (m, 4H, H-9 and H-10 ), 4.69 (m, 1H, H-3), 4.59 (t,
3
+
ꢀ
1H, H-17, J = 8.4 Hz), 2.25 (q, 4H, H-2 , J = 16.2 Hz, 7.8 Hz), 2.01 (m,
H, H-8 , H-11 ), 0.83 (s, 3H, H-19), 0.77 (s, 3H, H-18), 0.88 (t, 6H,
ꢀ ꢀ
8
ꢀ
13
2.3.2. Estradiol dilinoleate 7
H-18 , J = 6.45 Hz). C NMR (acetone-d6) ı: 37.62 (C-1), 25.92 (C-2),
73.75 (C-3), 2.73 (C-4), 43.56 (C-5), 28.38 (C-6), 32.38 (C-7), 37.93
(C-8), 55.19 (C-9), 36.41 (C-10), 21.55 (C-11), 36.22 (C-12), 45.56
(C-13), 51.62 (C-14), 24.22 (C-15), 30.57 (C-16), 83.02 (C-17), 12.64
Colorless liquid, Rf in 5:1 n-hexane/EtOAc is 0.62. 1H NMR
(
(
8
4
0
1
(
(
1
6
1
CDCl ) ı: 7.27 (d, peak overlapped with CHCl peak, 1H, H-1), 6.83
3
3
dd, 1H, H-2, J = 8.4 Hz, 2.4 Hz), 6.77 (d, 1H, H-4, J = 2.4 Hz), 5.35 (m,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ ꢀ ꢀ
(C-18), 173.62, 173.20 (C-1 ), 35.05 (C-2 ), 25.83 (C-3 ), 28.38–30.57
H, H-9 , H-10 , H-12 , and H-13 ), 4.7 (t, 1H, H-17, J = 8.4 Hz), 2.77 (t,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
H, H-11 , J = 5.55 Hz), 2.04 (m, 8H, H-8 , H-14 ), 0.89 (t, 6H, H-18 ),
(C-4 , C-5 , C-6 , C-7 , C-12 , C-13 , C-14 , C-15 ), 130.69, 130.61 (C-9
.82 (s, 3H, H-18). 1 C NMR (CDCl ) ı: 126.56 (C-1), 118.79 (C-2),
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
and C-10 ), 27.88 (C-8 and C-11 ), 30.68 (C-16 ), 23.42 (C-17 ), 14.46
3
ꢀ
+
48.73 (C-3), 121.7 (C-4), 138.31 (C-5), 27.82 (C-7), 38.45 (C-8), 44.2
C-9), 137.94 (C-10), 26.26 (C-11), 37.12 (C-12), 43.14 (C-13), 50.06
C-14), 23.49 (C-15), 27.25 (C-16), 82.59 (C-17), 12.3 (C-18), 174.10,
72.77 (C-1 ), 34.81, 34.63 (C-2 ), 25.32, 25.20 (C-3 ), 29.34–29.8 (C-
, C-4 –C-7 and C-12 –C-15 ), 130.43, 130.25 (C-9 , C-13 ), 128.23,
(C-18 and C-19). MS m/z (relative intensity) 820 M (very small),
539 (16), 265 (21), 257 (46), 163 (14), 95 (18).
ꢀ
ꢀ
ꢀ
2.3.6. 5˛-Androstane-3ˇ,17ˇ-diol dilinoleate 15
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Colorless liquid, R in 4.5:1 n-hexane/EtOAc is 0.62. 1H NMR
f
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
28.12 (C-10 , C-12 ), 22.78 (C-17 ), 14.28 (C-18 ). MS m/z (relative
intensity) 796 M (8), 534 (40), 272 (48), 255 (100), 159 (37), 133
(CDCl ) ı: 5.35 (m, 8H, H-9 , H-10 , H-12 , H-13 ), 4.54 (m, 1H, H-
3
+
ꢀ
3), 4.52 (q, 1H, H-17, J = 9 Hz, 7.8 Hz), 2.77 (t, 4H, H-11 , J = 5.85 Hz),
ꢀ
ꢀ
ꢀ
(
17).
2.26 (m, 4H, H-2 ), 2.04 (m, 8H, H-8 , H-11 ), 0.77 (s, 3H, H-18),
ꢀ
.83 (s, 3H, H-19), 0.89 (t, 6H, H-18 , J = 6.9 Hz). C NMR (CDCl ) ı:
3
13
0
2
.3.3. 5-Androsten-3ˇ-ol-17-one oleate 11
37.14 (C-1), 27.41 (C-2), 73.54 (C-3), 34.81 (C-4), 42.9 (C-5), 34.26
(C-7), 35.77 (C-8), 54.39 (C-9), 35.49 (C-10), 20.88 (C-11), 37.14 (C-
12), 44.86 (C-13), 50.91 (C-14), 23.76 (C-15), 31.73 (C-16), 82.77
Colorless liquid, Rf in 5:1 n-hexane/EtOAc is 0.58. 1H NMR
ꢀ ꢀ
CDCl ) ı: 5.41 (d, 1H, H-6, J = 4.5 Hz), 5.34 (m, 2H, H-9 and H-10 ),
3
(
ꢀ
ꢀ
ꢀ ꢀ
(C-17), 12.43 (C-18), 174.11, 173.62 (C-1 ), 34.96 (C-2 ), 25.31 (C-
4
.6 (m, 1H, H-3), 2.27 (t, 2H, H-2 , J = 7.5 Hz), 2.00 (m, 4H, H-8 and
ꢀ
ꢀ ꢀ ꢀ ꢀ ꢀ ꢀ
3 ), 27.79–29.55 (C-6, C-4 , C-5 , C-6 , C-7 , C-15 ), 130.43, 130.27
H-11 ), 1.05 (s, 3H, H-19), 0.88 (overlapped peaks, 6H, H-18 and H-
1
ꢀ
13
ꢀ ꢀ ꢀ ꢀ ꢀ
(C-9 and C-10 ), 128.25, 128.13, (C-12 and C-13 ), 27.7 (C-8 and
8 ). C NMR (CDCl ) ı: 37.15 (C-1), 27.94 (C-2), 73.62 (C-3), 38.32
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(
C-4), 140.22 (C-5), 122.01 (C-6), 31.68 (C-7), 31.62 (C-8), 50.4 (C-9),
C-14 ), 25.84 (C-11 ), 29.80 (C-16 ), 22.78 (C-17 ), 14.27 (C-18 and
+
3
2
1
6.94 (C-10), 20.52 (C-11), 30.98 (C-12), 47.71 (C-13), 51.92 (C-14),
2.07 (C-15), 36.01 (C-16), 221.18 (C-17), 13.73 (C-18), 19.54 (C-
C-19). MS m/z (relative intensity) 816 M (1), 537 (1.5), 257 (11.5).
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
9), 173.47 (C-1 ), 34.98 (C-2 ), 25.23 (C-3 ), 29.28–29.96 (C-4 –C-7
2.3.7. 4-Androsten-17ˇ-ol-3-one oleate 17
ꢀ
ꢀ
ꢀ
ꢀ
Colorless liquid, Rf in 5:1 n-hexane/EtOAc is 0.23. 1H NMR
and C-12 –C15 ), 27.36 (C-8 ), 27.94 (C-11 ), 130.2, 129.96 (C-9 and
C-10 ), 32.09 (C-16 ), 22.87 (C-17 ) 14.3 (C-18 ). MS m/z (relative
intensity) 552 M (very small), 270 (31), 255 (14), 145 (8), 121 (23),
1
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ ꢀ
(CDCl ) ı: 5.73 (s, 1H, H-4), 5.34 (m, 2H, H-9 and H-10 ), 4.61 (q, 1H,
3
+
ꢀ
H-17, J = 9.15 Hz, 7.65 Hz), 2.29 (t, 2H, H-2 , J = 7.55 Hz), 2.00 (m, 4H,
ꢀ
ꢀ
ꢀ
07 (11).
H-8 and H-11 ), 1.19 (s, 3H, H-19), 0.88 (t, 3H, H-18 , J = 6.75 Hz),
0
.84 (s, 3H, H-18). 13C NMR (CDCl ) ı: 35.63 (C-1), 34.76 (C-2),
3
2
.3.4. 5-Androsten-3ˇ-ol-17-one linoleate 12
199.58 (C-3), 124.16 (C-4), 171.08 (C-5), 32.94 (C-6), 32.10 (C-7),
35.63 (C-8), 53.93 (C-9), 38.81 (C-10), 20.75 (C-11), 36.86 (C-12),
42.72 (C-13), 50.47 (C-14), 23.69 (C-15), 27.71 (C-16), 82.36 (C-17),
Colorless liquid, Rf in 3:1 n-hexane/EtOAc is 0.73. 1H NMR
ꢀ
(
CDCl ) ı: 5.39–5.25 (d, 1H and m, 4H overlapped, H-6 and H-9 ,
3
ꢀ
ꢀ
ꢀ
ꢀ ꢀ ꢀ
12.26 (C-18), 17.6 (C-19), 174.03 (C-1 ), 34.12 (C-2 ), 25.3 (C-3 ),
H-10 , H-12 , H-13’), 4.6 (m, 1H, H-3), 2.74 (t, 2H, H-11 , J = 5.7 Hz),
2
3
ꢀ
ꢀ
ꢀ
ꢀ ꢀ ꢀ ꢀ ꢀ ꢀ ꢀ ꢀ
29.30–29.96 (C-4 , C-5 , C-6 , C-7 , C-12 , C-13 , C-14 , and C-15 ),
.03 (m, 4H, H-8 and H-14 ), 2.27 (t, 2H, H-2 , J = 7.5 Hz), 1.02 (s,
ꢀ
13
ꢀ ꢀ ꢀ ꢀ
130.20, 129.94 (C-9 and C-10 ), 27.37, 27.42 (C-8 and C-11 ), 31.70
H, H-19), 0.86 (overlapped peaks, 6H, H-18 and H-18 ). C NMR
ꢀ
ꢀ
ꢀ
(
(
CDCl ) ı: 37.16 (C-1), 27.96 (C-2), 73.64 (C-3), 38.34 (C-4), 140.2
C-5), 122.02 (C-6), 31.64 (C-7), 31.7 (C-8), 50.38 (C-9), 36.96 (C-10),
(C-16 ), 22.87 (C-17 ), 14.31 (C-18 ). MS m/z (relative intensity) 552
3
+
M (14), 271 (38), 147 (6).
2
1
0.54 (C-11), 30.99 (C-12), 47.72 (C-13), 51.93 (C-14), 22.09 (C-
5), 36.05 (C-16), 221.19 (C-17), 13.75 (C-18), 19.55 (C-19), 173.46
2
.3.8. 4-Androsten-17ˇ-ol-3-one linoleate 18
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(
C-1 ), 34.89 (C-2 ), 25.24 (C-3 ), 29.3–29.8 (C-4 –C-7 ), 27.4 (C-8 ),
Colorless liquid, Rf in 3:1 n-hexane/EtOAc is 0.30. 1H NMR
ꢀ ꢀ ꢀ ꢀ
1
30.42, 130.26, 128.25, 128.12 (C-9 , C-10 , C-12 and C-13 ), 22.78
(CDCl ) ı: 5.73 (s, 1H, H-4), 0.84 (s, 3H, H-18), 1.19 (s, 3H, H-
3
ꢀ
ꢀ
+
(
(
C-17 ), 14.27 (C-18 ). MS m/z (relative intensity) 550 M (9), 270
93), 255 (47), 145 (30), 121 (63).
ꢀ ꢀ ꢀ ꢀ
9), 5.35 (m, 4H, H-9 , H-10 , H-12 and H-13 ), 4.6 (q, 1H, H-17,
1
ꢀ
ꢀ
J = 9.3 Hz, 7.5 Hz), 2.77 (t, 2H, H-11 , J = 5.55 Hz), 2.29 (t, 2H, H-2 ,