R. Kaur et al. / European Journal of Medicinal Chemistry 46 (2011) 1356e1366
1363
yield. ½a 2D5
ꢃ
þ22.3 (c 0.1, CHCl3), mp 113e115 ꢀC 1H NMR (200 MHz,
39.6, 41.5, 42.7, 46.7, 47.4, 54.4, 54.8, 59.2, 65.7, 113.8, 120.1, 122.7,
140.8, 167.9, 172.3, 190.5. ESI-MS (m/z): 556 [M þ Na]þ. Anal. Calc.
for C35H51NO3: C, 78.75; H, 9.63; N, 2.62. Found: C, 78.47; H, 9.82;
N, 2.72.
CDCl3):
d 0.81, 0.89, 0.90, 1.04, 1.08, 1.14, 1.26, 1.63 (24H, 23, 25, 26,
27, 28, 29 & 30 eCH3CH3 & eCH3CH2CH3), 4.03 (m, 2H, eCH3OCH2),
5.16 (brs, 1H, H at C12), 8.04 (s, 1H, eCH3CH]N). 13C NMR (100 MHz,
CDCl3):
d 13.5, 14.6, 16.6, 17.5, 19.1, 20.0, 21.3, 23.8, 24.5, 24.8, 26.5,
27.3, 28.3, 28.8, 30.5, 31.1, 31.3, 33.3, 34.1, 38.6, 39.9, 41.7, 42.5, 43.8,
45.7, 46.6, 55.8, 59.6, 65.1, 111.0, 124.3, 139.9, 149.8, 167.2, 172.4. ESI-
MS (m/z): 558 [M þ Na]þ. Anal. Calc. for C35H53NO3: C, 78.46;
H, 9.97; N, 2.61. Found: C, 78.23; H, 10.13; N, 2.72.
4.1.14. Butyl 2-cyano-3,11-dioxo-urs-1,12-dien-24-oate (18)
The compound 18 was prepared from 16 following the same
procedure as for 17. ½a D25
ꢃ
þ58.0 (c 0.1, CHCl3), mp 156e158 ꢀC 1H
NMR (200 MHz, CDCl3):
d
0.79, 0.91, 1.23, 1.28, 1.30, 1.41, 1.52, 1.58
(24H, 23, 25, 26, 27, 28, 29 & 30 eCH3 & eCH2CH3), 4.03 (m, 2H,
4.1.10. Butyl 11-oxoisoxazole[4,5-b]urs-12-en-24-oate (14)
eOCH2), 5.67 (brs, 1H, H-12), 8.54 (s, 1H, H-1). 13C NMR (125 MHz,
The compound 14 was prepared from 12 following the same
CDCl3): d 13.6, 15.4, 17.4, 18.6, 18.8, 19.1, 20.4, 20.8, 21.1, 27.2, 28.9,
procedure as for 13. ½a D25
ꢃ
þ44.3 (c 0.1, CHCl3), mp 109e111 ꢀC 1H
29.4, 29.7, 30.8, 31.8, 32.1, 33.8, 39.2, 39.9, 40.8, 44.1, 45.4, 53.6, 54.0,
54.7, 59.1, 65.8, 113.3, 114.6, 129.6, 167.6, 170.3, 171.9, 190.1, 197.5.
ESI-MS (m/z): 570 [M þ Na]þ. Anal. Calc. for C35H49O4: C, 76.74;
H, 9.02; N, 2.56. Found: C, 77.02; H, 9.21; N, 2.67.
NMR (200 MHz, CDCl3):
d
0.80, 0.85, 0.92, 1.07, 1.17, 1.23, 1.28, 1.61
(24H, 23, 25, 26, 27, 28, 29 & 30 eCH3 & eCH2CH3), 3.97 (m, 2H,
eOCH2), 5.56 (brs, 1H, H-12), 8.01 (s, 1H, -CH]N). 13C NMR
(50 MHz, CDCl3):
d 13.9, 15.4, 17.8, 18.2, 19.4, 20.8, 21.5, 23.1, 24.8,
27.7, 27.9, 29.3, 30.1, 30.6, 31.3, 32.3, 34.4, 36.7, 38.2, 39.7, 39.8, 41.3,
44.2, 45.2, 55.4, 59.5, 60.2, 65.5, 111.6, 130.8, 150.4, 166.3, 166.7,
172.9,199.1. ESI-MS (m/z): 572 [M þ Na]þ. Anal. Calc. for C35H51NO4:
C, 76.46; H, 9.35; N, 2.55. Found: C, 76.21; H, 9.53; N, 2.64.
4.1.15. Butyl 2-cyano-3-hydroxy-urs-12-en-24-oate (19)
A solution of 17 (500 mg) in MeOH (20 ml), sodium borohydride
(350 mg) was added at 0 ꢀC. After completion the reaction was
diluted with water, extraction with DCM (3 ꢁ 100 ml), usual
workup and chromatography of the crude product on a silica gel
column using hexane: ethyl acetate (99:1 to 90:10) as eluant, gave
4.1.11. Butyl 2-cyano-3-oxo-urs-12-en-24-oate (15)
Sodium methoxide (2 g, 37 mmol) was added to a solution of 13
(700 mg, 1.3 mmol) in MeOH and Et2O at 0 ꢀC. The mixture was
stirred for 1 h and slowly brought it to room temperature and kept it
on stirring for 4e5 h. Product formed was extracted with DCM and
was purified by column chromatography. After completion, treat-
ment with 1.5 N aq. hydrochloric acid, extraction with DCM
(3 ꢁ 100 ml), usual workup and chromatography of the crude
product on a silica gel column using hexane: ethyl acetate (99:1 to
compound 19 in 90% yield as white powder. ½a D25
ꢃ
þ37.0 (c 0.1,
CHCl3), mp 146e148 ꢀC 1H NMR (500 MHz, CDCl3):
d
0.79, 0.83,
0.87, 0.94, 0.97, 1.01, 1.07, 1.12 (24H, 23, 25, 26, 27, 28, 29 & 30 eCH3
& eCH2CH3), 3.23 (brs, 1H, H-2), 3.67 (brs, 1H, H-3), 4.08 (m, 2H,
eOCH2), 5.14 (brs, 1H, H-12). 13C NMR (125 MHz, CDCl3):
d 11.3,13.6,
16.6, 16.7, 17.5, 21.4, 22.3, 22.5, 23.4, 23.6, 25.8, 26.3, 26.9, 28.4, 28.7,
31.1, 32.6, 33.8, 34.7, 37.4, 39.6, 41.4, 41.8, 42.3, 46.7, 47.2, 53.5, 56.1,
59.1, 63.8, 71.2, 121.1, 121.5, 139.9, 179.8. ESI-MS (m/z): 560
[M þ Na]þ. Anal. Calc. for C35H55NO3: C, 78.16; H, 10.31; N, 2.60.
Found: C, 77.89; H, 10.54; N, 2.45.
90:10) as eluant, gave 15 (yield 95%) as white solid. ½a D25
ꢃ
þ12.3 (c 0.1,
CHCl3), mp 116e118 ꢀC 1H NMR (200 MHz, CDCl3):
d 0.80, 0.87, 0.91,
0.94, 1.05, 1.07, 1.09, 1.43 (24H, 23, 25, 26, 27, 28, 29 & 30 eCH3
eCH2CH3), 4.11 (m, 2H, eOCH2), 5.14 (brs, 1H, H-12). 13C NMR
(125 MHz, CDCl3): 13.6, 13.7, 16.8, 17.5, 20.5, 20.7, 21.4, 23.2, 23.6,
23.7, 24.8, 28.0, 28.8, 30.3, 31.2, 32.3, 33.8, 34.2, 34.6, 36.8, 37.6, 39.6,
39.7, 41.5, 44.2, 46.4, 57.9, 58.1, 59.1, 65.7, 116.9, 123.4, 140.2, 145.6,
173.0. ESI-MS (m/z): 549 [M þ Na]þ. Anal. Calc. for C35H53NO3: C,
78.46; H, 9.97; N, 2.61. Found: C, 78.26; H, 10.11; N, 2.69.
&
4.1.16. Butyl 2-cyano-3-hydroxy-11-oxo-urs-12-en-24-oate (20)
The compound 20 was prepared from 18 following the same
d
procedure as for 19. ½a D25
ꢃ
þ48.0 (c 0.1, CHCl3), mp 157e159 ꢀC 1H
NMR (500 MHz, CDCl3):
d
0.78, 0.83, 0.92, 0.95, 1.20, 1.28, 1.39, 1.49
(24H, 23, 25, 26, 27, 28, 29 & 30 eCH3 & eCH2CH3), 3.30 (1H, H-2),
3.75 (1H, H-3), 4.10 (m, 2H, eOCH2), 5.58 (brs, 1H, H-12). 13C NMR
(125 MHz, CDCl3):
d 14.5, 16.9, 18.6, 19.4, 20.6, 21.1, 22.8, 25.2, 25.5,
4.1.12. Butyl 2-cyano-3,11-dioxo-urs-12-en-24-oate (16)
27.5, 27.8, 28.9, 31.1, 31.8, 33.1, 34.1, 37.3, 37.8, 39.5, 39.6, 40.9, 41.1,
44.1, 45.0, 47.9, 56.8, 59.3, 60.8, 63.9, 75.8, 120.6, 130.6, 164.9, 176.1,
197.7. ESI-MS (m/z): 574 [M þ Na]þ. Anal. Calc. for C35H53NO4:
C, 76.18; H, 9.68; N, 2.54. Found: C, 76.28; H, 9.91; N, 2.72.
The compound 16 was prepared from 14 following the same
procedure as for 15. ½a D25
ꢃ
þ38.7 (c 0.1, CHCl3), mp 122e124 ꢀC 1H
NMR (200 MHz, CDCl3) :
d 0.81, 0.94, 1.21, 1.25, 1.28, 1.31, 1.54, 2.04
(24H, 23, 25, 26, 27, 28, 29 & 30 eCH3 & eCH2CH3), 4.10 (m, 2H,
eOCH2), 5.57 (brs, 1H, H-12). 13C NMR (125 MHz, CDCl3):
d
13.4,
4.1.17. 2-Carbamoyl-3-hydroxy-urs-12-en-24-oic acid (21)
13.5, 17.3, 18.2, 19.1, 19.4, 20.3, 20.7, 21.0, 22.6, 27.2, 28.3, 28.8, 29.6,
30.2, 31.2, 31.4, 33.9, 37.1, 39.0, 39.2, 40.9, 43.8, 44.7, 45.1, 57.8, 58.9,
59.3, 65.7, 116.5, 129.9, 166.2, 172.4, 173.9, 198.1. ESI-MS (m/z): 572
[M þ Na]þ. Anal. Calc. for C35H51NO4: C, 76.46; H, 9.35; N, 2.55.
Found: C, 76.25; H, 9.50; N, 2.62.
Potassium hydroxide was added (170 mg) to a solution of 19
(400 mg) in methanol: water (80:20) and kept it on refluxing. After
completion of the reaction, pH was adjusted to 7 using dil. HCl,
extraction with DCM (3 ꢁ 100 ml), usual workup and chromatog-
raphy of the crude product on a silica gel column using hexane:
ethyl acetate (99:1 to 90:10) as eluant, gave 21 (yield 92%). ½a D25
ꢃ
4.1.13. Butyl 2-cyano-3-oxo-urs-1,12-dien-24-oate (17)
þ40.7 (c 0.1, CHCl3), mp 174e176 ꢀC 1H NMR (500 MHz, CDCl3):
A mixture of 15 (500 mg, 0.93 mmol) and DDQ (300 mg,
1.3 mmol) in dry toluene was heated under reflux for 1 h. Reaction
mixture was then subjected to filtration. The filtrate obtained was
evaporated under vacuum and was subjected to chromatography
on a silica gel column using hexane: ethyl acetate (99:1 to 90:10) as
d 0.78, 0.87, 0.96, 0.98,1.02,1.06,1.12 (21H, 23, 25, 26, 27, 28, 29 & 30
eCH3), 3.10 (brs, 1H, H-2), 4.06 (m, 1H, H-3), 5.11 (m, 1H, H-12). 13
NMR (125 MHz, CDCl3): 11.3, 13.6, 14.2, 16.7, 17.4, 20.1, 21.3, 22.3,
C
d
25.7, 26.1, 26.9, 28.1, 28.8, 32.5, 33.7, 34.8, 37.3, 39.7, 41.5, 42.8, 46.7,
47.5, 48.8, 56.2, 59.1, 63.5, 69.5, 121.5, 139.6, 177.9, 178.5. ESI-MS
(m/z): 522 [M þ Na]þ. Anal. Calc. for C31H49NO4: C, 74.51; H, 9.88;
N, 2.80. Found: C, 74.28; H, 10.13; N, 2.97.
eluant, gave 17 in 90% yields as white solid. ½a D25
ꢃ
þ34.7 (c 0.1,
CHCl3), mp 135e138 ꢀC 1H NMR (200 MHz, CDCl3):
d
0.80, 0.83,
0.88, 1.07, 1.11, 1.16, 1.18, 1.52 (24H, 23, 25, 26, 27, 28, 29 & 30 eCH3 &
eCH2CH3), 3.90 (m, 2H, eOCH2), 5.17 (brs, 1H, H-12), 7.66 (s, 1H,
4.1.18. 2-Carbamoyl-3-hydroxy-11-oxours-12-en-24-oic acid (22)
The compound 22 was prepared from 20 following the same
H-1). 13C NMR (125 MHz, CDCl3):
d
13.7, 14.3, 17.6, 19.2, 19.4, 20.9,
21.4, 23.2, 23.8, 26.5, 27.9, 28.5, 30.2, 31.2, 32.8, 33.4, 33.9, 34.8, 37.1,
procedure as for 21. ½a D25
ꢃ
þ39.5 (c 0.1, CHCl3), mp 190e192 ꢀC 1H