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R. C. Santos et al. / Bioorg. Med. Chem. 17 (2009) 6241–6250
pressure to give a yellowish solid. This solid was crystallized from
4.1.1.7. 3-Oxolup-20(29)-en-28-oic acid (11). Details of the syn-
thesis of this compound were reported previously.4 Compound 11
methanol to yield compound 5 (129 mg, 83%): IR (film) mmax 3320,
3070, 1720, 1643 cmꢀ1; 1H NMR (CDCl3, 300 MHz) d 4.71 (br s, 1H,
(685 mg, 67%): IR (film) mmax 3070, 1703, 1686, 1642 cmꢀ1 1H
;
H-29a), 4.58 (br s, 1H, H-29b), 3.67 (s, 3H, COOCH3), 3.18 (dd, 1H,
J = 10.9 Hz, J = 4.5 Hz, H-3a) 2.43 (m, 1H, H-19), 1.69 (s, 3H, H-
30), 0.96 (s, 3H), 0.94 (3H), 0.92 (s, 3H), 0.82 (s, 3H), 0.75 (s, 3H);
13C NMR (CDCl3, 75 MHz) d 177.2 (C28), 149.7 (C20), 110.1 (C29),
80.6 (C3); EI-MS m/z (% rel. intensity): 470 (25) M+, 286 (26), 253
(52), 247 (29), 203 (36), 192 (100), 189 (100), 175 (64), 119 (47),
105 (51).
NMR (CDCl3, 300 MHz) d 4.77 (br s, 1H, H-29a), 4.64 (br s, 1H, H-
29b), 3.04 (dt, J = 10.7 Hz, J = 4.3 Hz, 1H, H-19), 1.72 (s, 3H, H-30),
1.09 (s, 3H), 1.04 (s, 3H), 1.02 (s, 3H), 0.99 (s, 3H), 0.95 (s, 3H); 13C
NMR (CDCl3, 75 MHz) d 218.2 (C3), 182.2 (C28), 150.3 (C20), 109.7
(C29); EI-MS m/z (% rel. intensity): 454 (19) M+, 408 (24), 393 (20),
248 (85), 189 (100), 175 (62), 133 (55), 119 (76), 105 (69), 79 (52).
4.1.1.8. 3-Oxolup-1,20(29)-dien-28-oic acid (12). A solution of
compound 11 (400 mg, 0.88 mmol) and DDQ (597 mg, 2.64 mmol)
in anhydrous dioxane (18 ml) was heated under reflux and N2
atmosphere for 15 h. After the reaction mixture was diluted in
ethyl acetate (60 ml) and the insoluble matter was removed by fil-
tration. The filtrate was washed with saturated solution of Na2CO3
(3 ꢁ 30 ml), and then with water (30 ml) and brine (30 ml), dried
with anhydrous Na2SO4, filtered and concentrated under reduced
pressure to give a yellowish solid. This solid was submitted to
FCC with petroleum ether 40–60 °C/ethyl acetate (4:1) to afford
compound 12 (179 mg, 45%); IR (film) mmax 3070, 1730, 1689,
4.1.1.4. Lup-20(29)-en-3b,28-di-yl acetate (6). Details of the
synthesis of this compound were reported previously.54 Compound
6 (373 mg, 89%): IR (film) mmax 3073, 1735, 1642, 1241, 880 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 4.69 (br s, 1H, H-29a) 4.59 (br s, 1H, H-
29b), 4.47 (dd, J = 10.3 Hz, J = 5.8 Hz, 1H, H-3 ), 4.25 (d, J = 11.1 Hz,
a
1H, H-28a), 3.85 (d, J = 11.1 Hz, 1H, H-28b), 2.45 (dt, J = 10.9 Hz,
J = 5.8 Hz, 1H, H-19), 2.07 (s, 3H, OCOCH3), 2.04 (s, 3H, OCOCH3),
1.68 (s, 3H, H-30), 1.03 (s, 3H), 0.97 (s, 3H), 0.84 (s, 6H), 0.83 (s,
3H); 13C NMR (CDCl3, 75 MHz) d 171.6 (OCOCH3), 171.0 (OCOCH3),
150.1 (C20), 109.9 (C29), 80.9 (C3), 62.8 (C28); EI-MS m/z (% rel.
intensity): 526 (5) M+, 466 (72), 216 (46), 203 (47), 202 (44), 190
(53), 189 (100), 187 (68), 119 (47), 91 (51).
1645 cmꢀ1 1H NMR (CDCl3, 400 MHz) d 7.11 (d, J = 10.3 Hz, 1H,
;
H-1), 5.80 (d, J = 10.3 Hz, 1H, H-2), 4.76 (s, 1H, H-29a), 4.63 (s,
1H, H-29b), 3.03 (m, 1H, H-19), 1.70 (s, 3H, H-30), 1.13 (s, 3H),
1.07 (s, 3H), 1.06 (s, 3H), 1.02 (s, 3H), 0.99 (s, 3H); 13C NMR (CDCl3,
100 MHz) d 205.9 (C3), 181.7 (C28), 160.1 (C1), 150.2 (C20), 125.1
(C2), 109.9 (C29); EI-MS m/z (% rel. intensity): 452 (17) M+, 213
(100), 150 (39), 137 (34), 95 (31), 91 (42), 81 (36), 79 (41), 77
(29), 67 (34).
4.1.1.5. 30-Methoxylup-20-(29)-en-3b,28-diol
bromolup-20(29)-en-3b,28-diol (8). Details of the synthesis of
these compounds were reported previously.31 Compound
(1.4 g, 64%): IR (film)
max 3347, 3073, 1645 cmꢀ1; 1H NMR (CDCl3,
(7) and 30-
7
m
300 MHz) d 4.92 (s, 1H, H-29a), 4.91 (s, 1H, H-29b), 3.86 (br s, 2H,
H-30), 3.78 (d, J = 10.5 Hz, 1H, H-28a), 3.35 (s, 3H, OCH3), 3.31 (d,
J = 10.5 Hz, 1H, H-28b), 3.18 (dd, J = 10.8 Hz, J = 5.2 Hz, 1H, H-3a),
4.1.1.9. 2-Hydroxy-3-oxolup-1,20(29)-dien-28-oic
(13). Details of the synthesis of these compounds were reported
previously.57 Compound 13 (273 mg, 73%):
max 3389, 3073, 1730,
acid
2.28 (dt, J = 10.8 Hz, J = 5.4 Hz, 1H, H-19) 1.02 (s, 3H), 0.98 (s,
3H), 0.97 (s, 3H), 0.82 (s, 3H), 0.76 (s, 3H); 13C NMR (CDCl3,
75 MHz) d 150.9 (C20), 109.0 (C29), 78.9 (C3), 74.8 (C30), 60.2
(C28), 58.3 (OCH3); EI-MS m/z (% rel. intensity): 473 (25) M+, 201
(93), 189 (86), 187 (100), 145 (75), 131 (66), 121 (71), 119 (73),
95 (66), 81 (69). Compound 8 (451 mg, 18%): IR (film) mmax 3371,
m
1698, 1669, 1645 cmꢀ1; 1H NMR (CDCl3, 300 MHz) d 6.45 (s, 1H, H-
1), 4.75 (s, 1H, H-29a), 4.64 (s, 1H, H-29b), 3.02 (m, 1H, H-19), 1.70
(s, 3H, H-30), 1.20 (s, 3H), 1.13 (s, 3H), 1.10 (s, 3H), 1.00 (s, 3H),
0.98 (s, 3H); 13C NMR (CDCl3, 75 MHz) d 201.2 (C3), 182.4 (C28),
150.1 (C20), 143.9 (C2), 128.9 (C1), 109.9 (C29); EI-MS m/z (% rel.
intensity): 469 (11) M+, 321 (43), 213 (100), 189 (32), 150 (45),
136 (29), 91 (63), 80 (34), 75 (54), 69 (65).
3075, 1642 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 5.12 (s, 1H, H-
;
29a), 5.03 (s, 1H, H-29b), 3.99 (s, 2H, H-30), 3.81 (d, J = 10.8 Hz,
1H, H-28a), 3.33 (d, J = 10.8 Hz, 1H, H-28b), 3.19 (dd, J = 10.9 Hz,
J = 5.1 Hz, 1H, H-3a), 2.39 (dt, J = 11.0 Hz, J = 5.3 Hz, 1H, H-19)
4.1.1.10. 3b-Hydroxy-lup-20(29)-en-28-yl-1H-imidazole-1-car-
boxylate (14) and lup-20(29)-en-3b,28-di-yl-(1H-imidazole-1-
1.03 (s, 3H), 0.99 (s, 3H), 0.97 (s, 3H), 0.82 (s, 3H), 0.76 (s, 3H);
13C NMR (CDCl3, 75 MHz) d 151.0 (C20), 109.8 (C29), 78.9 (C3),
60.3 (C28). EI-MS m/z (% rel. intensity): 522 (3) M+, 121 (74), 119
(91), 107 (85), 105 (82), 93 (84), 91 (91), 81 (84), 79 (100), 67 (82).
carboxylate) (15). To
a solution of compound 1 (200 mg,
0.45 mmol) in anhydrous THF (8 ml), CDI (219 mg, 1.35 mmol)
was added. After 7 h under magnetic stirring at reflux temperature
and N2 atmosphere, the reaction was completed as verified by TLC
control. The reaction mixture was poured onto water (30 ml) and
extracted with diethyl ether (3 ꢁ 30 ml). The combined organic ex-
tract was then washed with water (30 ml), and brine (30 ml), dried
with anhydrous Na2SO4, filtered and concentrated under reduced
pressure to give a yellowish solid. This solid was submitted to
FCC with petroleum ether 40–60 °C/ethyl acetate (3:2) and affor-
ded compound 14 (152 mg, 63%): mp (acetone) 202–204 °C; IR
4.1.1.6. 3b,28-Dihydroxy-(20R)-lupan-29-al (9) and 3b,28-dihy-
droxy-(20S)-lupan-29-al (10). Details of the synthesis of these
compounds were reported previously.55,58 Compound 9 (354 mg,
39%): IR (film) mmax 3393, 1714 cmꢀ1 1H NMR (CDCl3, 300 MHz)
;
d 9.86 (d, J = 2.0 Hz, 1H, H-29), 3.77 (d, J = 10.8 Hz, 1H, H-28a),
3.26 (d, J = 10.8 Hz, 1H, H-28b), 3.20 (dd, J = 10.9 Hz, J = 5.1 Hz,
1H, H-3a) 2.60 (m, 1H, H-20), 1.10 (d, J = 6.9 Hz, 3H, H-30), 1.03
(s, 3H), 0.98 (s, 3H), 0.95 (s, 3H), 0.84 (s, 3H), 0.77 (s, 3H); 13C
NMR (CDCl3, 75 MHz) d 206.8 (CHO), 78.9 (C3), 60.2 (C28); EI-MS
m/z (% rel. intensity): 458 (2) M+, 369 (100), 207 (43), 192 (51),
189 (72), 161 (67), 133 (31), 121 (31), 107 (36), 95 (33). Compound
(film) mmax 3570, 3078, 1751, 1645, 880 cmꢀ1 1H NMR (CDCl3,
;
300 MHz) d 8.26 (s, 1H, H-20), 7.46 (br s, 1H, H-50), 7.13 (br s, 1H,
H-40), 4.72 (d, J = 1.4 Hz, 1H, H-29a), 4.67–4,63 (m, 2H, H-28a and
H-29b), 4.21 (d, J = 10.7 Hz, 1H, H-28b), 3.19 (dd, J = 10.8 Hz,
10 (179 mg, 20%): IR (film)
300 MHz) d 9.62 (s, 1H, H-29), 3.80 (d, J = 10.8 Hz, H-28a), 3.33 (d,
J = 10.8 Hz, 1H, H-28b), 3.20 (dd, J = 10.9 Hz, J = 5.1 Hz, 1H, H-3 ),
m
max 3340, 1716 cmꢀ1; 1H NMR (CDCl3,
J = 5.2 Hz, 1H, H-3a), 2.47 (dt, J = 10.7 Hz, J = 5.6 Hz, 1H, H-19),
1.70 (s, 3H, H-30), 1.06 (s, 3H), 1.01 (s, 3H), 0.97 (s, 3H), 0.83 (s,
3H), 0.76 (s, 3H); 13C NMR (CDCl3, 75 MHz) d 149.5 (C20), 148.7
(OCO), 136.8 (C20), 129.6 (C40), 117.2 (C50), 110.3 (C29), 78.9 (C3),
67.5 (C28); EI-MS m/z (% rel. intensity): 536 (12) M+, 207 (36),
189 (39), 187 (54), 119 (44), 107 (34), 105 (34), 91 (46), 79 (38),
69 (100) and compound 15 (56 mg, 20%): mp (acetone/n-hexane)
a
2.65 (m, 1H, H-20), 1.06 (s, 3H), 1.04 (d, J = 7.0 Hz, 3H, H-30),
0.98 (s, 6H), 0.84 (s, 3H), 0.77 (s, 3H); 13C NMR (CDCl3, 75 MHz) d
204.8 (CHO), 78.9 (C3), 60.2 (C28); EI-MS m/z (% rel. intensity):
458 (4) M+, 369 (76), 207 (48), 190 (46), 189 (100), 161 (70), 119
(51), 105 (46), 95 (47), 91 (59).
161–163 °C; IR (film) mmax 3070, 1757, 1642, 880 cmꢀ1 1H NMR
;