1-Hexanoyl-4-(3,28-diacetylbetulin-30-yl)-aminothiourea (4f). Yield 0.437 g (61.8%), C H N O S. PMR
41 67
3 5
spectrum (300 MHz, CDCl , ꢂ, ppm, J/Hz): 0.83, 0.84, 0.98, 1.03 (15H, 4s, 5CH ), 2.04 and 2.07 (6H, both s, 2OCOCH ),
3
3
3
2.23–2.44 (3H, m, H-19, COCH ), 3.81 (1H, d, J = 11.1, H-28), 4.11–4.33 (3H, m, H-30, H-28), 4.59 (1H, dd, J = 5.1, 9.6, H-3),
2
4.78 and 4.88 (2H, both s, H-29), 7.21, 8.95, 9.60 (3H, each br.s, 3NH).
5-Alkyl-4-(betulin-30-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (5a–f). Asolution of 3 (0.35 mmol) in a mixture
of ethanol (4.8 mL), THF (6.7 mL) and 4N NaOH (2.6 mL) was refluxed for 5–6 h. After cooling to room temperture, the
mixture was acidified with 10%AcOH until pH 6–7 and concentrated under reduced pressure. Then 20 mL of dichloromethane
and 10 mL of water were added, and the organic phase was separated, washed with water, dried, and evaporated. The residue
was purified by silica-gel column chromatography.
4-(Betulin-30-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (5a). Yield 0.101 g (54.6%), mp 186.2–186.7ꢃC,
–1
C H N O S. IR spectrum (KBr, ꢁ, cm ): 3414 (OH, NH), 1649, 1556 (C=C, C=N), 1269, 1211 (C=S), 1028 (C-O). PMR
32 51
3 2
spectrum (300 MHz, CDCl , ꢂ, ppm, J/Hz): 0.76, 0.83, 0.97, 1.00, 1.03 (each 3H, s, CH ), 2.30–2.45 (1H, m, H-19), 3.20 (1H,
3
3
dd, J = 4.8, 10.8, H-3), 3.29 and 3.78 (2H, both d, J = 10.8, H-28), 4.55 and 4.68 (2H, both d, J
(1H, both s, 2H-29), 7.76 (1H, s, triazole). MS (Maldi-TOF, DITH as matrix): m/z (100%): 510.28 [M – CH OH] , 527.11
[M + H – CH ] , 580.32 [M + K] .
= 16.2, H-30), 4.64 and 5.06
gem
+
2
+
+
3
5-Methyl-4-(betulin-30-yl)-2,4-dihydro-3H-1, 2, 4-triazole-3-thione (5b). Yield 0.120 g (59.4%), mp 198.1–198.6ꢃC,
–1
C H N O S. IR spectrum (KBr, ꢁ, cm ): 3374 (OH, NH), 1649, 1585 (C=C, C=N), 1251, 1192 (C=S), 1038 (C-O).
33 53
3 2
PMR spectrum (300 MHz, CDCl , ꢂ, ppm, J/Hz): 0.76, 0.83, 0.97, 1.00, 1.03 (each 3H, s, CH ), 2.31 (3H, s, CH ), 2.33–2.51
3
3
3
(1H, m, H-19), 3.20 (1H, dd, J = 5.1, 10.8, H-3), 3.32 and 3.79 (2H, both d, J = 10.8, H-28), 4.34 and 4.96 (2H, both s, H-29),
+
4.49 and 4.70 (2H, both d, J
= 16.8, H-30). MS (Maldi-TOF, DITH as matrix): m/z (100%): 524.38 [M – CH OH] , 541.16
gem
2
+
+
[M + H – CH ] , 594.37 [M + K] .
3
5-Ethyl-4-(betulin-30-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (5c). Yield 0.132 g (61.9%), mp 214.2–214.7ꢃC,
–1
C H N O S. IR spectrum (KBr, ꢁ, cm ): 3389 (OH, NH), 1647, 1576 (C=C, C=N), 1261, 1186 (C=S), 1028 (C-O).
34 55
3 2
PMR spectrum (300 MHz, CDCl , ꢂ, ppm, J/Hz): 0.76, 0.82, 0.97, 1.00, 1.02 (each 3H, s, CH ), 1.23 (3H, t, J = 7.2, CH CH ),
3
3
2
3
2.28–2.52 (1H, m, H-19), 2.53 (2H, q, J = 7.2, CH CH ), 3.20 (1H, dd, J = 4.8, 10.8, H-3), 3.32 and 3.79 (2H, both d,
2
3
J = 10.8, H-28), 4.30 and 4.94 (2H, both s, H-29), 4.50 and 4.69 (2H, both d, J
matrix) m/z (100%): 538.44 [M – CH OH] , 555.27 [M + H – CH ] , 608.48 [M + K] .
= 16.5, H-30). MS (Maldi-TOF, DITH as
gem
+
+
+
2
3
5-Propyl-4-(betulin-30-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (5d). Yield 0.068 g (33.6%), mp 190.5–190.9ꢃC,
–1
C H N O S. IR spectrum (KBr, ꢁ, cm ): 3352 (OH, NH), 1647, 1577 (C=C, C=N), 1335, 1275, (C=S), 1049 (C-O).
35 57
3 2
PMR spectrum (300 MHz, CDCl , ꢂ, ppm, J/Hz): 0.76, 0.83, 0.97, 1.01, 1.03 (each 3H, s, CH ), 2.35–2.49 (1H, m, H-19), 2.53
3
3
(2H, t, J = 7.5, CH CH CH ), 3.20 (1H, dd, J = 4.8, J = 10.8, H-3), 3.33 and 3.79 (2H, both d, J = 10.8, H-28), 4.26 and 4.94
2
2
3
(2H, both s, H-29), 4.51 and 4.67 (2H, both d, J
[M – CH OH] , 569.30 [M + H – CH ] , 622.51 [M + K] .
= 16.8, H-30). MS (Maldi-TOF, DITH as matrix) m/z (100%): 552.46
gem
+
+
+
2
3
5-Butyl-4-(betulin-30-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (5e). Yield 0.112 g (54.2%), mp 188.4–188.9ꢃC,
–1
C H N O S. IR spectrum (KBr, ꢁ, cm ): 3379 (OH, NH), 1647, 1574 (C=C, C=N), 1277, 1184 (C=S), 1031 (C-O).
36 59
3 2
PMR spectrum (300 MHz, CDCl , ꢂ, ppm, J/Hz): 0.76, 0.83, 0.97, 1.00, 1.03 (each 3H, s, CH ), 2.35–2.50 (1H, m, H-19), 2.55
3
3
(2H, t, J = 7.2, CH (CH ) CH ), 3.20 (1H, dd, J = 4.8, 10.8, H-3), 3.33 and 3.79 (2H, both d, J = 10.8, H-28), 4.24 and 4.94
2
2 2
3
(2H, both s, H-29), 4.53 and 4.66 (2H, both d, J
[M – CH OH] , 583.32 [M + H – CH ] , 636.53 [M + K] .
= 16.8, H-30). MS (Maldi-TOF, DITH as matrix) m/z (100%): 566.49
gem
+
+
+
2
3
5-Pentyl-4-(betulin-30-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (5f). Yield 0.137 g (63.1%), mp 234.3–234.6ꢃC,
–1
C H N O S. IR spectrum (KBr, ꢁ, cm ): 3356 (OH, NH), 1649, 1577 (C=C, C=N), 1292, 1253 (C=S), 1026 (C-O).
37 61
3 2
PMR spectrum (300 MHz, CDCl , ꢂ, ppm, J/Hz): 0.76, 0.83, 0.85, 0.97, 1.03 (each 3H, s, CH ), 2.35–2.68 (3H, m, H-19,
3
3
CH (CH ) CH ), 3.14–3.28 (1H, m, H-3), 3.33 and 3.79 (1H, both d, J = 10.5, H-28), 4.25 and 4.94 (1H, both s, H-29),
2
2 3
3
+
+
4.45–4.75 (2H, m, H-30). MS (Maldi-TOF, DITH as matrix) m/z (100%): 580.52 [M – CH OH] , 597.37 [M + H – CH ] ,
650.56 [M + K] .
2
3
+
REFERENCES
1.
2.
I.-C. Sun, J.-K. Shen, H.-K. Wang, L. M. Cosentino, and K.-H. Lee, Bioorg. Med. Chem. Lett., 8, 1267 (1998).
K. Qian, D. Yu, C.-H. Chen, L. Huang, S. L. Morris-Natschke, T. J. Nitz, K. Salzwedel, M. Reddick, G. P. Allaway,
and K.-H. Lee, J. Med. Chem., 52, 3248 (2009).
266