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R. Gaware et al. / Bioorg. Med. Chem. 19 (2011) 1866–1880
2.80–2.64 (m, 1H), 2.15- 2.31 (m, 4H), 2.03 (s, 3H), 1.40- 1.97 (m,
19H), 1.32 (s, 3H), 1.30 (s, 3H), 1.13 (s, 3H), 1.10 (s, 3H), 0.89 (s,
6H), 0.79 (s, 3H). 13C NMR (50 MHz, CDCl3): d 200.41, 171.03,
170.10, 158.86, 128.06, 80.58, 61.71, 54.95, 52.28, 52.18, 46.59,
45.45, 43.33, 43.09, 38.89, 38.01, 36.87, 35.78, 32.67, 31.88,
31.28, 28.54, 28.39, 28.01, 26.20, 23.53, 23.16, 21.30, 18.64,
17.32, 16.66, 16.37. HRMS: calcd [M+H]+: 527.3843, found
[M+H]+: 527.3842.
4.11. N-[(3b,18b,20b)-3-(Acetoxy)-11-oxo-30-norolean-12-en-20-
yl]-N0-[(trifluoromethyl)sulfonyl] urea (5e)
Prepared according to general procedure (A) from 4 (200.0 mg,
0.39 mmol) and trifluoro methane sulfonamide (87.0 mg,
0.58 mmol) to give 5e as a white powder (110.0 mg, 42%, HPLC
>99%). 1H NMR (200 MHz, pyridine-d5): d 5.76 (s, 1H), 4.79–2.64
(m, 1H), 3.18–2.90 (m, 1H), 2.44–2.70 (m, 22H), 2.03 (s, 3H), 1.43
(s, 3H), 1.36 (s, 3H), 1.23 (s, 3H), 1.05 (s, 3H), 0.90 (s, 3H), 0.89 (s,
3H), 0.77 (s, 3H). 13C NMR (50 MHz, pyridine-d5): d 199.96,
171.08, 170.15, 162.28, 128.84, 80.93, 62.31, 55.50, 53.57, 47.48,
45.92, 44.02, 42.03, 39.61, 38.71, 37,82, 36.43, 33.23, 33.03,
32.43, 28.96, 28.60, 28.55, 27.12, 27.05, 24.44, 23.79, 21.58,
19.18, 18.08, 17.44, 17.13. CI-MS, m/z (Irel. (%)): 675.89 [M+NH4]+
(1.0); 526.86 (45.03); 525.90 (100.00); 525.01 (38.22); 524.19
(45.03); 523.33 (24.61); 510.98 (28.27); 510.98 (28.27); 509.92
(58.90); 466.92 (31.67); 190.97 (45.80); 95.04 (24.07). Anal. Calcd
for C33H49F3N2O6S: C, 60.13; H, 7.50; N, 4.25; F, 8.65; S, 4.87.
Found: C, 58.15; H, 7.95; N, 3.88; F, 7.88; S, 4.43.
4.8. N-Hydroxy-N-methyl-N0-[(3b,18b,20b)-3-(acetoxy)-11-oxo-
30-norolean-12-en-20-yl] urea (5b)
Prepared according to general procedure (B) from 4 (100.0 mg,
0.20 mmol) and N-methyl-hydroxylamine hydrochloride (25.0
mg, 0.30 mmol) to yield 5b as a white powder (70.0 mg, 64%, HPLC
>99%). 1H NMR (200 MHz, CDCl3): d 5.61 (s, 1H), 4.59–2.42 (m, 1H),
3.09 (s, 3H), 2.85–2.67 (m, 1H), 2.41–2.75 (m, 22H), 2.04 (s, 3H),
1.34 (s, 3H), 1.33 (s, 3H), 1.14 (s, 3H), 1.10 (s, 3H), 0.86 (s, 6H),
0.81 (s, 3H). 13C NMR (50 MHz, CDCl3): d 200.87, 171.03, 170.36,
160.98, 128.12, 80.51, 61.71, 54.96, 52.33, 47.08, 45.54, 43.41,
42.85, 38.77, 38.73, 38.02, 36.93, 35.69, 32.68, 31.87, 31,38,
28.44, 28.27, 28.00, 26.34, 26.20, 23.52, 23.10, 21.28, 18.66,
17.30, 16.66, 16.39. CI-MS, m/z (Irel. (%)): 556.94 [M]+ (18.94),
556.02 (8.10), 552.95 (10.79), 552.25 (5.70), 543.04 (17.38),
541.86 (21.09), 540.77 (100.00), 539.79 (46.27), 538.45 (11.70),
468.09 (15.48). Anal. Calcd for C33H52N2O5: C, 71.19; H, 9.41; N,
5.03. Found: C, 67.15; H, 8.91; N, 4.67.
4.12. N-[(3b,18b,20b)-3-(Acetoxy)-11-oxo-30-norolean-12-en-20-
yl]-N0-(phenylmethyl) urea (5f)
Prepared according to general procedure (A) from 4 (200.0 mg,
0.39 mmol) and benzyl amine (63.0 mg, 0.59 mmol) to yield 5f as a
white powder (160.0 mg, 66%, HPLC >99%). 1H NMR (200 MHz,
CDCl3): d 7.32–2.20 (m, 5H), 5.56 (s, 1H), 4.57–2.42 (m, 1H),
4.41–2.12 (m, 2H), 2.84–2.60 (m, 1H), 2.29–2.70 (m, 22H), 2.03
(s, 3H),1.29 (m, 6H), 1.13 (s, 3H), 1.09 (s, 3H), 0.86 (m, 6H), 0.71
(s, 3H). 13C NMR (50 MHz, CDCl3): d 200.08, 171.07, 169.62,
157.95, 139.55, 128.60, 128,45, 128.13, 127.14, 80.60, 61.68,
54.95, 52.40, 46.54, 45.41, 44.24, 43.41, 43.28, 38.80, 38.01,
36.83, 35.74, 32.66, 31.79, 31.12, 28.71, 28.28, 28.02, 26.32,
26.14, 23.50, 23.20, 21.30, 18.62, 17.34, 16.67, 16.37. HRMS: calcd
[M+H]+: 617.4313, found [M+H]+: 617.4326.
4.9. N-Hydroxy-N0-[(3b,18b,20b)-3-(acetoxy)-11-oxo-30-norolean-
12-en-20-yl] urea (5c)
Prepared according to general procedure (B) from 4 (200.0 mg,
0.39 mmol) and hydroxylamine hydrochloride (41.0 mg,
0.59 mmol) to give 5c as a white powder (120.0 mg, 56%, HPLC
>97%). 1H NMR (200 MHz, CDCl3): d 5.81 (s, 1H), 5.70 (s, 1H),
4.60–2.42 (m, 1H), 2.84–2.69 (m, 1H), 2.35- 0.75 (m, 22H), 2.04
(s, 3H), 1.33 (m, 6H), 1.13, (s, 3H), 1.09 (s, 3H), 0.86 (m, 6H), 0.81
(s, 3H). 13C NMR (50 MHz, CDCl3): d 201.04, 171.01, 170.61,
161.23, 128.12, 80.52, 61.67, 54.94, 52.58, 47.04, 45.46, 43.34,
41.27, 38.74, 38.02, 36.96, 35.54, 32.89, 32.69, 31.82, 28.47,
28.30, 28.01, 26.41, 26.31,23.52, 23.02, 21.29, 18.68, 17.29, 16.66,
16.40. CI-MS, m/z (Irel. (%)): 560.02 [M+NH4]+ (1.17), 559.12
(0.57), 526.58 (18.41), 525.53, (27, 45), 524.49 (17.07), 510.97
(38.73), 509.96 (100.00), 299.87 (19.35), 259.02 (19.22), 134.99
(15.95). Anal. Calcd for C32H50N2O5: C, 70.81; H, 9.29; N, 5.16.
Found: C, 68.52; H, 9.51; N, 4.81.
4.13. N-[(3b,18b,20b)-3-(Acetoxy)-11-oxo-30-norolean-12-en-20-
yl]-1,2-hydrazinedicarboxamide (5g)
Prepared according to general procedure (B) from 4 (200.0 mg,
0.39 mmol)
and
semicarbazide
hydrochloride
(66.0 mg,
0.59 mmol) to give 5g as a white powder (130 mg, 57%, HPLC
>99%). 1H NMR (200 MHz, pyridine-d5): d 5.78 (s, 1H), 4.80–2.64
(m, 1H), 3.15–2.90 (m, 1H), 2.44–2.70 (m, 25H), 2.03 (s, 3H), 1.52
(s, 3H), 1.25 (s, 3H), 1.22 (s, 3H), 1.00 (s, 3H), 0.89 (s, 3H), 0.88 (s,
3H), 0.77 (s, 3H). 13C NMR (50 MHz, pyridine-d5): d 199.74,
171.03, 169.98, 162.08, 159.43, 128.92, 80.89, 62.21, 55.43, 52.99,
47.42, 45.89, 43.93, 42.17, 39.48, 38.70, 37.78, 36.57, 33.36,
33.16, 32.44, 29.16, 28.91, 28.55, 27.10, 26.92, 24.42, 23.76,
21.57, 19.15, 18.05, 17.45, 17.13. CI-MS, m/z (Irel. (%)): 584.83
[M]+ (6.72), 583.91 (5.47), 559.02 (6.06), 523.51 (10.68), 522.58
(13.67), 510.96 (40.53), 509.96 (100.00), 508.81 (6.52), 484.89
(16.29), 483.98 (49.73). HRMS: calcd [M+H]+: 585.4010, found
[M+H]+: 585.4017.
4.10. N-Methylsulfonyl-N0-[(3b,18b,20b)-3-(acetoxy)-11-oxo-30-
norolean-12-en-20-yl] urea (5d)
Prepared according to general procedure (A) from 4 (200.0 mg,
0.39 mmol) and methane sulfonamide (56.0 mg, 0.59 mmol) to
yield 5d as a white powder (120.0 mg, 50.6%, HPLC >96%). 1H
NMR (200 MHz, CDCl3): d 5.62 (s, 1H), 4.60–2.42 (m, 1H), 3.24 (s,
3H), 2.80–2.65 (m, 1H), 2.33 (s, 1H), 2.17–0.70 (m, 21H), 2.05 (s,
3H), 1.36 (s, 3H), 1.33 (s, 3H), 1.14 (s, 3H), 1.11 (s, 3H), 0.87 (m,
6H), 0.84 (s, 3H). 13C NMR (50 MHz, CDCl3): d 200.38, 171.13,
169.26, 150.74, 128.26, 80.58, 61.73, 54.93, 53.71, 46.73, 45.48,
43.30, 42.10, 42.02, 38.75, 38.01, 36.88, 35.69, 32.65, 31.86,
31.32, 28.40, 28.01, 27.86, 26.31, 26.10, 23.51, 23.20, 21.31,
18.63, 17.30, 16.66, 16.37. CI-MS, m/z (Irel. (%)): 621.54 [M+NH4]+
(3.76), 578.54 (10.81), 526.43 (18.45), 525.49 (15.89), 524.43
(12.16), 511.01 (31.94), 509.98, (100.00), 508.96 (6.39), 485.80
(2.90), 484.91 (13.99). Anal. Calcd for C33H52N2O6S: C, 65.53; H,
8.67; N, 4.63; S, 5.30. Found: C, 62.84; H, 9.04; N, 4.19; S, 4.89.
4.14. N0-(2-Hydroxyethyl)-N-[(3b,18b,20b)-3-(acetoxy)-11-oxo-
30-norolean-12-en-20-yl] urea (5h)
Prepared according to general procedure (A) from 4 (100.0 mg,
0.1961 mmol) and ethanol amine (21.4 mg, 0.35 mmol) to yield 5h
as a white powder (70.0 mg, 63%, HPLC >99%). 1H NMR (200 MHz,
CDCl3): d 5.65 (s, 1H), 4.47–2.39 (m, 1H), 3.60 (s, 2H), 3.24 (s, 2H),
2.67–2.61 (m, 1H), 2.28 (s, 1H), 2.11-0.5 (m, 22H), 1.98 (s, 3H), 1.27
(s, 3H), 1.22 (s, 3H), 1.06 (s, 3H), 1.04 (s, 3H), 0.80 (m, 6H), 0.73 (s,
3H). 13C NMR13C NMR (50 MHz, CDCl3): d 201.28. 171.32, 170.94,
159.63, 127.88, 80.45, 63.08, 61.71, 54.91, 52.31, 46.60, 45.57,