Luận án Tổng hợp và khảo sát hoạt tính gây độc tế bào của các dẫn xuất mới của Artemisinin

; tìm thấy: 630.32911 [M 
+H]
+
. 
Piperidin-1-yl(4-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-
3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)-1H-1,2,3-
triazol-1-yl)phenyl)methanone (61f) 
47 
Chất rắn màu trắng: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (99: 1: 
0.1); 51 %. đnc 127–128 C. IR (KBr, v (cm-1)): 1688, 1567, 1469, 1451, 1389, 
1162, 1102, 1038, 985, 937. 
1
H NMR (500 MHz, CDCl3) δ (ppm): 8,01 (s, 1H, H-
3´); 8,05 (d, J = 8,0 Hz, 2H, H-6´); 7,58 (d, J =8,0 Hz, 2H, H-5´); 5,45 (s, 1H, H-
12); 5,03 (d, J = 13,0 Hz, 1H, H-1´); 4,98 (d, J = 3,5 Hz, 1H, H-10); 4,78 (d, J = 
13,0 Hz, 1H, H-1´); 3,73 (brs, 4H, H-1´´); 2,68 (m, 1H, H-9); 2,38–2,35 (m, 1H, H-
4α); 2,07–2,02 (m, 1H, H-4β); 1,91–1,86 (m, 2H, H-8α, H-5α); 1,80–1,75 (m, 1H, 
H-8β); 1,63–1,53 (m, 5H, H-7β, H-2´´); 1,51–1,48 (m, 4H, H-3´´, H-8α, H-5β); 1,46 
(s, 3H, H-14); 1,35–1,31 (m, 1H, H-6); 1,27–1,22 (m, 1H, H-5α); 0,93 (overlap, 7H, 
H-7α, H-15, H-16). 13C NMR (125 MHz, CDCl3) δ (ppm): 168,7 (C= O); 145,9 (C-
2´); 137,4 (C-4´); 136,7 (C-7´); 128,4 (C-6´); 120,6 (C-5´); 120,3 (C-3´); 104,1 (C-
3); 101,8 (C-10); 87,9 (C-12); 80,9 (C-12a); 61,6 (C-10); 53,4 (C-5a); 52,4 (C-1´´); 
44,3 (C-8a); 37,3 (C-6); 36,3 (C-4); 34,5 (C-7); 30,8 (C-9); 26,0 (C-14); 25,5 (C-
2´´); 24,6 (C-5, C-3´´); 24,3 (C-8); 20,2 (C-15); 12,9 (C-16). ESI-HRMS: lý thuyết: 
C30H41N4O6: 553.30261; tìm thấy: 553.30213 [M + H]
+
. 
48 
(4-Methylpiperidin-1-yl)(4-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-
trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-
yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)methanone (61g) 
Chất dầu: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (99: 1: 0.1); 49 %. 
IR (film, v (cm
-1
)): 1678, 1577, 1489, 1461, 1382, 1152, 1109, 1039, 988, 932. 1H 
NMR (500 MHz, CDCl3) δ (ppm): 8,01 (s, 1H, H-3´); 7,81 (d, J = 8,5 Hz, 2H, H-
6´); 7,58 (d, J = 8,5 Hz, 2H, H-5´); 5,45 (s, 1H, H-12); 5,03 (d, J = 12,5 Hz, 1H, H-
1´); 4,98 (d, J = 3,5 Hz, 1H, H-10); 4,79 (d, J = 12,5 Hz, 1H, H-1´); 3,71 (brs, 2H, 
H-1´´); 3,05 (brs, 2H, H-1´´); 2,71–2,65 (m, 1H, H-9); 2,41–2,34 (m, 1H, H-4α); 
2,07–2,03 (m, 1H, H-4β); 1,91–1,86 (m, 2H, H-8α, H-5α); 1,82–1,75 (m, 3H, H-8β, 
H-2´´); 1,72–1,59 (m, 2H, H-7β, H-3´´); 1,52–1,47 (m, 2H, 8α, H-5β); 1.,44 (s, 3H, 
H-14); 1,37–1,30 (m, 1H, H-6); 1,28–1,21 (m, 3H, H-2´´, H-5α); 1,0 (d, J = 6,5 Hz, 
3H, H-4´´); 0,94 (t, 7H, H-7α, H-15, H-16). 13C NMR (125 MHz, CDCl3) δ (ppm): 
168,7 (C=O); 145,9 (C-2´); 137,5 (C-4´); 136,7 (C-7´); 128,4 (C-6´); 120,6 (C-5´); 
120.3 (C-3´); 104,0 (C-3); 101,8 (C-10); 87,9 (C-12); 80,9 (C-12a); 61,5 (C-10); 
53,4 (C-5a); 52,4 (C-1´´); 44,3 (C-8a); 37,3 (C-6); 36,3 (C-4); 34,5 (C-7); 33,7 (C-
2´´); 30,9 (C-3´´); 30,7 (C-9); 26,0 (C-14); 24,6 (C-5); 24,4 (C-8); 21,6 (C-4´´); 20,2 
(C-15); 12,9 (C-16). ESI-HRMS: lý thuyết: C31H43N4O6: 567.31826; tìm thấy: 
567.31820 [M + H]
+
. 
49 
(2-Methylpiperidin-1-yl)(4-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-
trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-
yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)methanone (61h) 
Chất dầu: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (99: 1: 0.1); 55 %. 
IR (film, v (cm
-1
)): 1668, 1557, 1479, 1451, 1375, 1167, 1102, 1033, 988, 939. 
1
H 
NMR (500 MHz, CDCl3) d (ppm): 7,85 (s, 1H, H-3´); 7.80 (d, J = 8,5 Hz, 2H, H-
6´); 7,56 (d, J = 8,5 Hz, 2H, H-5´); 5,44 (s, 1H, H-12); 5,03 (d, J = 12.5 Hz, 1H, H-
1´); 4,98 (d, J = 3,5 Hz, 1H, H-10); 4,77 (d, J = 12,5 Hz, 1H, H-1´); 3,52 (m, 1H, H-
1´´); 3,06 (brs, 2H, H-5´´); 2,67 (m, 1H, H-9); 2,41–2,35 (m, 1H, H-4α); 2,07–2,02 
(m, 1H, H-4β); 1,91–1,85 (m, 2H, H-8α, H-5α); 1,82–1,71 (m, 1H, H-8β); 1,64–
1,57 (m, 3H, H-7β, H-2´´); 1,53–1,48 (m, 6H, H-8α, H-5β, H-3´´, H-4´´); 1,46 (s, 
3H, H-14); 1,36–1,30 (1H, H-6); 1,28–1,21 (m, 4H, H-6´´, H-5α); 0,94–0,92 
(overlap, 7H, H-7α, H-15, H-16). 13C NMR (125 MHz, CDCl3) δ (ppm): 168,7 
(C=O); 146,0 (C-2´); 138,8 (C-4´); 137,2 (C-7´); 129,9 (C-6´); 120,6 (C-3´); 120,5 
(C-5´); 104,2 (C-3); 101,9 (C-10); 87,9 (C-12); 81,1 (C-12a); 61,7 (C-1´); 53,4 (C-
5a); 52,5 (C-1´´); 44,4 (C-8a, C-5´´); 37,3 (C-6); 36,4 (C-4); 34,5 (C-7); 30,8 (C-9); 
29,6 (C-2´´); 26,1 (C-14); 24,6 (C-4´´); 24,4 (C-3´´); 24,2 (C-5); 24,0 (C-8); 20,3 
(C- 6´´); 18,8 (C-15); 12,9 (C-16). ESI-HRMS: lý thuyết: C31H43N4O6: 567.31826; 
tìm thấy: 567.31820 [M + H]+. 
50 
Pyrrolidin-1-yl(4-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-
3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)-1H-1,2,3-
triazol-1-yl)phenyl) methanone (61i) 
Chất rắn màu trắng: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (99: 1: 
0.1); 50 %. Mp 140–141 oC. IR (KBr, v (cm-1)): 1659, 1557, 1469, 1462, 1385, 
1165, 1105, 1035, 989, 939. 
1
H NMR (500 MHz, CDCl3) δ (ppm): 8,03 (s, 1H, H-
3´); 7,84 (d, J = 8,5 Hz, 2H, H-6´); 7,59 (d, J = 8,5 Hz, 2H, H-5´); 5,45 (s, 1H, H-
12); 5,03 (d, J = 12.5 Hz, 1H, H-1´); 4,98 (d, J = 3,5 Hz, 1H, H-10); 4,77 (d, J = 
12,5 Hz, 1H, H-1´); 3,68 (t, J = 7,0 Hz, 2H, H-1´´); 3,47 (t, J = 7,0 Hz, 2H, H-1´´); 
2,68 (m, 1H, H-9); 2,38 (dt, J = 4,0 Hz, 14,0 Hz, 1H, H-4α); 2,35 (m, 4H, H-4β, H-
1´´); 1,95–1,85 (m, 4H, H-8α, H-5β, H-1´´); 1,64–1,59 (m, 1H, H-7β); 1,53–1,47 
(m, 2H, H-8α, H-5β); 1,46 (s, 3H, H-14); 1,35–1,27 (m, 1H, H-6); 1,26–1,22 (m, 
1H, H-5α); 0,93 (overlap, 7H, H-7α, H-15, H-16). 13C NMR (125 MHz, CDCl3) d 
(ppm): 168,0 (C=O); 145,8 (C-2´); 137,7 (C-4´); 137,3 (C-7´); 128,7 (C-6´); 
120,6(C-5´); 120,0 (C-3´); 104,0 (C-3); 101,7 (C-10); 87,8 (C-12); 80,9 (C-12a); 
61,5 (C-10); 52,4 (C-5a); 49,5 (C-1´´); 44,2 (C-8a); 37,2 (C-6); 36,3 (C-4); 34,4 (C-
7); 30,7 (C-9); 26,3 (C-14); 26,0 (C-2´´); 24,5 (C-5); 24,2 (C-8); 20,2 (C-15); 12,8 
(C-16). ESI-HRMS: lý thuyết: C29H39N4O6: 539.28696; tìm thấy: 539.28691 [M + 
H]
+
. 
51 
Morpholino(3-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-3H-
3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)-1H-1,2,3-triazol-1-
yl)phenyl)methanone (62a) 
Chất dầu: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (99: 1: 0.1); 49 %. 
IR (film, v (cm
-1
)): 1679, 1547, 1456, 1469, 1387, 1174, 1108, 1038, 987, 939. 
1
H 
NMR (500 MHz, CDCl3) δ (ppm): 8,08 (s, 1H, H-3´); 7,85–7,82 (m, 2H, H-7´, H-
8´); 7,59 (t, J = 1,5 Hz, 1H, H-5´); 7,48 (d, J = 7,5 Hz, 1H, H-9´); 5,45 (s, 1H, H-
12); 5,03 (d, J = 8,0 Hz, 1H, H-10); 4,98 (d, J = 3,5 Hz, 1H, H-10); 4,78 (d, J = 8,0 
Hz, 1H, H-10); 3,78 (brs, 4H, H-2´´); 3,58 (brs, 4H, H-1´´); 2,69–2,66 (m, 1H, H-9); 
2,38–2,32 (m, 1H, H-4α); 2,06–2,0 (m, 1H, H-4β); 1,91–1,86 (m, 2H, H-8α, H-5α); 
1,79–1,74 (m, 1H, H-8β); 1,64–1,60 (m, 1H, H-7β); 1,52–1,49 (m, 1H, H-8α); 1,46 
(s, 3H, H-14); 1,36–1,19 (m, 1H, H-6); 0,95 (overlap, 7H, H-7α, H-15, H-16). 13C 
NMR (125 MHz, CDCl3) δ (ppm): 168,7 (C=O); 146,0 (C-2´); 137,3 (C-6´); 137,0 
(C-9´); 130,1 (C-8´); 127,0 (C-4´); 121,8 (C-7´); 120,7 (C-5´); 119,3 (C-3´); 104,1 
(C-3); 101,8 (C-10); 87,9 (C-12); 81,0 (C-12a); 66,7 (C-1´´); 61,6 (C-1´); 53,4 (C-
2´´); 52,4 (C-5a); 44.3 (C-8a); 37,3 (C-6); 36,3 (C-4); 34,5 (C-7); 30,8 (C-9); 26,0 
(C-14); 24,6 (C-5); 23,7 (C-8); 20,2 (C-15); 12,9 (C-16). ESI-HRMS: lý thuyết: 
C29H39N4O7: 555.28187; tìm thấy: 555.28181 [M + H]
+
. 
52 
N,N-Diethyl-3-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-
3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)-1H-1,2,3-
triazol-1-yl)benzamide (62b) 
Chất dầu: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (99: 1: 0.1); 58 %. 
IR (film, v (cm
-1
)): 1672, 1549, 1446, 1461, 1387, 1171, 1100, 1032, 989, 939. 
1
H 
NMR (500 MHz, CDCl3) δ (ppm): 8,0 (s, 1H, H-3´); 7,81 (dd, J = 1,5 Hz, 8,5 Hz, 
1H, H-7´); 7,76 (m, 1H, H-5´); 7,58 (t, J = 9,0 Hz, 1H, H-8´); 7,45 (m, 1H, H-9´); 
5,44 (s, 1H, H-12); 5,03 (d, J = 12,5 Hz, 1H, H-1´); 4,98 (d, J = 3,5 Hz, 1H, H-10); 
4,78 (d, J = 12,5 Hz, 1H, H-1´); 3,58 (brs, 4H, H-1´´); 2,67 (m, 1H, H-9); 2,41–2,34 
(m, 1H, H-4α); 2,07–2,02 (m, 1H, H-4β); 1,91–1,86 (m, 1H, 2H, H-8α, H-5α); 
1,79–1,74 (m, 1H, H-8β); 1,64–1,60 (m, 1H, H-7β); 1,53–1,49 (m, 2H, H-8α, H-
5β); 1,46 (s, 9H, H-14, H-2´´); 1,35–1,21 (m, 1H, H-5α); 0,94 (overlap, 7H, H-7α, 
H-15, H-16). 
13
C NMR (125 MHz, CDCl3) δ (ppm): 169,5 (C=O); 145,9 (C-2´); 
138,9 (C-6´); 137,1 (C-9´); 129,9 (C-8´); 126,3 (C-4´); 121,1(C-7´); 120,7 (C-5´); 
118,6 (C-3´); 104,1 (C-3); 101,9 (C-10); 87.8 (C-12); 81,0 (C-12a); 61,7 (C-1´); 
52,4 (C-5a); 44,3 (C-8a); 44,0 (C-1´´); 37,3 (C-6); 36,3 (C-4); 34,5 (C-7); 30,8 (C-
9); 26,0 (C-14); 24,6 (C-5); 24,4 (C-8); 20,2 (C-15); 13,1 (C-16); 12,9 (C-2´´). ESI-
HRMS: lý thuyết: C29H41N4O6: 541.30261; tìm thấy: 541.30258 [M+H]
+
. 
53 
(4-Methylpiperazin-1-yl)(3-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-
trimethyldecahydro-3H-3,12epoxy[1,2]dioxepino[4,3-i]isochromen-10-
yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)methanone (62c) 
Chất dầu: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (98: 2: 0.1); 51 %. 
IR (film, v (cm
-1
)): 1688, 1541, 1444, 1468, 1385, 1176, 1106, 1033, 979, 935. 
1
H 
NMR (500 MHz, CDCl3) δ (ppm): 8,0 (s, 1H, H-3´); 7,85 (m, 1H, H-7´); 7,80 (m, 
1H, H-5´); 7,58 (t, J = 8,5 Hz, 1H, H-8´); 7,47 (dd, J = 1,5 Hz, 8,5 Hz, 1H, H-9´); 
5,45 (s, 1H, H-12); 5,03 (d, J = 13,0 Hz, 1H, H-1´); 4,98 (d, J = 3,5 Hz, 1H, H-10); 
4,78 (d, J = 13,0 Hz, 1H, H-1´); 3,82 (brs, 4H, H-1´´); 2,69–2,67 (m, 1H, H-9); 2,57 
(brs, 4H, H-2´´); 2,49–2,35 (m, 3H, H-3´´); 2,10–2,03 (m, 1H, H-4β); 1,92–1,86 (m, 
2H, H-8α, H-5α); 1,79–1,74 (1H, H-8β); 1,63–1,60 (m, 1H, H-7β); 1,52–1,47 (m, 
2H, H8α, H-5β); 1,45 (s, 3H, H-14); 1,35–1,30 (m, 1H, H-6); 1,27–1,21 (m,1H, H-
5α); 0,94 (overlap, 7H, H-7α, H-15, H-16). 13CNMR (125 MHz, CDCl3) δ (ppm): 
168,5 (C=O); 146,0 (C-2´); 137,5 (C-6´); 137,1 (C-9´); 129,8 (C-8´); 126,9 (C-4´); 
121,6 (C-7´); 120,7 (C-5´); 119,1 (C-3´); 104,1 (C-3); 101,9 (C-10); 87,9 (C-12); 
81,0 (C-12a); 61,6 (C-10); 55,1 (C-2´´); 53,4 (C-1´´); 52,4 (C-5a); 45,8 (C-3´´); 44,3 
(C-8a); 37,3 (C-6); 36,4 (C-4); 34,5 (C-7); 30,9 (C-9); 25,9 (C-14); 24,6 (C-5); 24,4 
(C-8); 20,2 (C-15); 12,9 (C-16). ESI-HRMS: lý thuyết: C30H42N5O6: 568.31351; tìm 
thấy: 568.31309 [M + H]+. 
54 
(4-Ethylpiperazin-1-yl)(3-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-
trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-
yl)oxy)methyl)-1H-1,2,3-triazol-1 yl)phenyl)methanone (62d) 
Chất dầu: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (98: 2: 0.1); 62 %. 
IR (film, v (cm
-1
)): 1676,1548, 1457, 1478, 1395, 1186, 1109, 1043, 979, 935. 
1
H 
NMR (500 MHz, CDCl3) δ (ppm): 8,0 (s, 1H, H-3´); 7,85(dt, J = 1,5 Hz, 8,5 Hz, 
1H, H-7´); 7,80 (s, 1H, H-5´); 7,58 (t, J = 8,5 Hz, 1H, H-8´); 7,47 (dd, J = 1,5 Hz, 
8,5 Hz, 1H, H-9´); 5,45 (s, 1H, H-12); 5,03 (d, J = 13,0 Hz, 1H, H-1´); 4,98 (d, J = 
3,5 Hz, 1H, H-10); 4,78 (d, J = 13,0 Hz, 1H, H-1´); 3,84 (brs, 4H, H-1´´); 2,69–2,67 
(m, 1H, H-9); 2,55 (brs, 4H, H-2´´); 2,49–2,35 (m, 3H, H-4α, H-3´´); 2,11–2,03 (m, 
1H, H-4β); 1,91–1,86 (m, 2H, H-8α, H-5α); 1,79–1,74 (m, 1H, H-8β); 1,63–1,60 
(m, 1H, H-7β); 1,52–1,47 (m, 2H, H-8α, H-5β); 1,45 (s, 3H, H-14); 1,35–1,30 (m, 
1H, H-6); 1,27–1,21 (m, 1H, H-5α); 1,12 (t, J = 7,0 Hz, 3H, H-4´´); 0,94 (overlap, 
7H, H-7α, H-15, H-16). 13C NMR (125 MHz, CDCl3) δ(ppm): 168, 4 (C=O); 145,9 
(C-2´); 137,6 (C-6´); 137,2 (C-9´); 129,9 (C-8´); 126,9 (C-4´); 121,6 (C-7´); 120,7 
(C-5´); 119,2 (C-3´); 104,1 (C-3); 101,9 (C-10); 87,9 (C-12); 81,0 (C-12a); 61,7 (C-
1´); 53,4(C-5a); 52,4 (C-2´´); 52,1 (C-1´´); 49,4 (C-3´´); 44,3 (C-8a); 37,3 (C-6); 
36,3 (C-4); 34,5 (C-7); 30,8 (C-9); 26,1 (C-14); 24,6 (C-5); 24,4 (C-8); 20,2 (C-15); 
12,9 (C-16); 11,8 (C-4´´). ESI-HRMS: lý thuyết: C31H44N5O6: 582.32916; tìm thấy: 
582.32909 [M + H]
+
. 
55 
(4-Phenylpiperazin-1-yl)(3-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-
trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-
yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)methanone (62e) 
Chất dầu: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (99: 0,5: 0,1); 57 %. 
IR (film, v (cm
-1
)): 1656, 1559, 1477, 1458, 1387, 1196, 1109, 1044, 978, 935. 
1
H 
NMR (500 MHz, CDCl3) δ (ppm): 8,02 (s, 1H, H-3´); 7,85 (d, J = 9,0 Hz, 2H, H-
5´´); 7,63 (d, J = 9,0 Hz, 2H, H-4´´); 7,29 (t, J = 8,0 Hz, 2H, H-8´, H-7´); 6,95–6,91 
(m, 3H, H-5´, H-9´, H-6´´); 5,45 (s, 1H, H-12); 5,03 (d, J = 13,0 Hz, 1H, H-1´); 4,98 
(d, J = 3,5 Hz, 1H, H-10); 4,79 (d, J = 13,0 Hz, 1H, H-1´); 3,62 (brs, 4H, H-1´´); 
3,19 (brs, 4H, H-2´´); 2,68 (m, 1H, H-9); 2,41–2,34 (m, 1H, H-4α); 2,08–2,02 (m, 
1H, H-4β); 1,91–1,86 (m, 2H, H-8α, H-5α); 1,81–1,75 (m, 1H, H-8β); 1,63–1,58 
(m, 1H, H-7β); 1,53–1,46 (m, 2H, H-8α, H-5β); 1,44 (s, 3H, H-14); 1,35–1,27 (m, 
1H, H-6); 1,26–1,22 (m, 1H, H-5α); 0,93 (overlap, 7H, H-7α, H-15, H-16). 13C 
NMR (125 MHz, CDCl3) δ (ppm): 168,6 (C=O); 150,7 (C-3´´); 146,0 (C-6´); 137,4 
(C-9´); 137,2 (C-4´); 130,1 (C-8´); 129,2 (C-4´); 127,0 (C-7´); 121,7 (C-6´´); 120,7 
(C-4´´); 119,3 (C-3´); 116,7 (C-5´); 104,1 (C-3); 101,9 (C-10); 87,9 (C-12); 81,0 
(C-12a); 61,6 (C-1´); 53,45 (C-2´´); 52,5 (C-5a); 48,7 (C-1´´); 44,3 (C-8a); 37,3 (C-
6); 36,3 (C-4); 34,5 (C-7); 30,8 (C-9); 26,1 (C-14); 24,6 (C-5); 24,4 (C-8); 20,2 (C-
15); 12,9 (C-16). ESI-HRMS: lý thuyết: C35H44N5O6: 630.32916; tìm thấy: 
630.32911 [M + H]
+
. 
56 
Piperidin-1-yl(3-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-
3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)-1H-1,2,3-
triazol-1-yl)phenyl)methanone (62f) 
Chất dầu: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (99: 1: 0,1); 60 %. 
IR (film, m (cm
-1
)): 1668, 1569, 1487, 1466, 1377, 1185, 1107, 1049, 977, 935. 
1
H 
NMR (500 MHz, CDCl3) δ (ppm): 8,0 (s, 1H, H-3´); 7,84 (m, 1H, H-7´); 7,78 (m, 
1H, H-5´); 7,58 (t, J = 8,0 Hz, 1H, H-8´); 7,45 (m, 1H, H-9´); 5,45 (s, 1H, H-12); 
5,03 (d, J = 12,5 Hz, 1H, H-1´); 4,98 (d, J = 3.5 Hz, 1H, H-10); 4,78 (d, J = 12,5 Hz, 
1H, H-1´); 3,74 (brs, 2H, H-1´´); 3,38 (brs, 2H, H-1´´); 2,68–2,66 (m, 1H, H-9); 
2,41–2,35 (m, 1H, H-4α); 2,07–2,03 (m, 1H, H-4β); 1,91–1,86 (m, 2H, H-8α, H-
5α); 1,79–1,74 (m, 2H, H-8β, H-3´´); 1,64–1,59 (m, 2H, H-7β, H-3´´); 1,58–1,53 
(m, 4H, H-2´´); 1,52–1,47 (m, 2H, H-8α, H-5β); 1,45 (s, 3H, H-14); 1,35–1,31 (m, 
1H, H-6); 1,27–1,21 (m, 1H, H-5α); 0,94 (overlap, 7H, H-7α, H-15, H-16). 13C 
NMR (125 MHz, CDCl3) δ (ppm): 168,5 (C=O); 145,9 (C-2´); 138,2 (C-6´); 137,1 
(C-9´); 129,8 (C-8´); 126,7 (C-4´); 121,3 (C-7´); 120,7 (C-5´); 118,9 (C-3´); 104,0 
(C-3); 101,8 (C-10); 87,9 (C-12); 81,0 (C-12a); 61,7 (C-1´); 53,4 (C-5a); 52,4 (C-
1´´); 44,3 (C-8a); 37,3 (C-6); 36,3 (C-4); 34,5 (C-7); 30,8 (C-9); 26,5 (C-14); 26,0 
(C-2´´); 24,6 (C-5); 24,1 (C-3´´); 23,6 (C-8); 20,2 (C-15); 12,9 (C-16). ESI-HRMS: 
lý thuyết: C30H41N4O6: 553.30261; tìm thấy: 553.30259 [M + H]
+
. 
57 
(4-Methylpiperidin-1-yl)(3-(4-((((3R,6R,9R,10S,12R,12aR)-,6,9-
trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-
yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)methanone (62g) 
Chất dầu: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (99: 1: 0,1); 59 %. 
IR (film, v (cm
-1
)): 1666, 1561, 1484, 1456, 1387, 1194, 1102, 1045, 977, 935. 
1
H 
NMR (500 MHz, CDCl3) δ (ppm): 7,99 (s, 1H, H-3´); 7,82 (m, 1H, H-7´); 7,77 (m, 
1H, H-5´); 7,57 (t, J = 7,5 Hz, 1H, H-8´); 7,46 (d, J = 7,5 Hz, 1H, H-9´); 5,45 (s, 1H, 
H-12); 5,03 (d, J = 13,0 Hz, 1H, H-1´); 4,98 (d, J = 3,5 Hz, 1H, H-10); 4,77 (d, J = 
13,0 Hz, 1H, H-1´); 3,71 (brs, 2H, H-1´´); 3,07 (brs, 2H, H-1´´); 2,68–2,66 (m, 1H, 
H-9); 2,40–2,35 (tt, 1H, J = 14,5, 10,5 Hz, 1H, H-4α); 2,06–1,92 (m, 1H, H-4β); 
1,89–1,75 (m, 2H, H-8α, H-5α); 1,73–1,61 (m, 3H, H-8β, H-3´´); 1,53–1,47 (m, 2H, 
H-8α, H-5β); 1,45 (s, 3H, H-14); 1,37–1,33 (m, 2H, H-2´´); 1,29–1,21 (m, 3H, H-
5α, H-2´´); 0,98 (d, J = 7,0 Hz, 3H, H-4´´); 0,93 (overlap, 7H, H-7α, H-15, H-16). 
13
C NMR (125 MHz, CDCl3) δ(ppm): 168,5 (C=O); 145,9 (C-2´); 138,3 (C-6´); 
137,2 (C-9´); 129,9 (C-8´); 126,8 (C-4´); 121,4 (C-7´); 120,7 (C-5´); 119,0 (C-3´); 
104,1 (C-3); 101,9 (C-10); 87,9 (C-12); 81,0 (C-12a); 61,7 (C-1´); 52,5 (C-5a); 48,0 
(C-1´´); 44,3 (C-8a); 37,3 (C-6); 36,3 (C-4); 34,5 (C-7); 31,0 (C-2´´); 29.5 (C-3´´); 
30,8 (C-9); 26,1 (C-14); 24,6 (C-5); 24,4 (C-8); 21,6 (C-4´´); 20,2 (C-15); 12,9 (C-
16). ESI-HRMS: lý thuyết: C31H43N4O6: 567.31826; tìm thấy: 567.31820 [M + H]
+
. 
58 
(2-Methylpiperidin-1-yl)(3-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-
trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-
yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)methanone (62h) 
Chất dầu: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (99: 1: 0,1); 63 %. 
IR (film, v (cm
-1
)): 1689, 1559, 1488, 1457, 1389, 1184, 1108, 1057, 979, 935. 
1
H 
NMR (500 MHz, CDCl3) δ (ppm): 7,99 (s, 1H, H-3´); 7,83 (d, J = 7,5 Hz, 1H, H-
7´); 7,75 (d, J = 1,5 Hz, 1H, H-5´); 7,57 (t, J = 7,5 Hz, 1H, H-8´); 7,43 (d, J = 7,5 
Hz, 1H, H-9´); 5,45 (s, 1H, H-12); 5,03 (d, J = 12,5 Hz, 1H, H-10); 4,98 (d, J = 3,5 
Hz, 1H, H-10); 4,78 (d, J = 12,5 Hz, 1H, H-1´); 3,51 (m, 1H, H-1´´); 3,09 (m, 2H, 
H-5´´); 2,67 (m, 1H, H-9); 2,41–2,34 (tt, 1H, J = 14,5; 10,5 Hz, 1H, H-4α); 2,07–
2,02 (m, 1H, H-4β); 1,82–1,69 (m, 3H, H-8β, H-3´´, H-2´´); 1,64–1,58 (m, 3H, H-
3´´, H-4´´, H-7β); 1,56–1,46 (m, 6H, H-8α, H-5β, H-4´´, H-3´´); 1,45 (s, 3H, H-14); 
1,35–1,22 (m, 5H, H-6, H-5α, H-6´´); 0,94 (overlap, 7H, H-7α, H-15, H-16). 13C 
NMR (125 MHz, CDCl3) δ (ppm): 168,7 (C=O); 146,0 (C-2´); 138,8 (C-6´); 137,2 
(C-9´); 129,9 (C-8´); 126,4 (C-4´); 121,3 (C-7´); 120,8 (C-5´); 118,7 (C-3´); 104,1 
(C-3); 101,9 (C-10); 87,9 (C-12); 81,1 (C-12a); 61,7 (C-1´); 53,4 (C-1´´); 52,5 (C-
5a); 44,6 (C-5´´); 44,4 (C-8a); 37,3 (C-6); 36,4 (C-4); 34,5 (C-7); 30,8 (C-9); 29,8 
(C-2´´); 26,1 (C-14); 24,6 (C-4´´); 24,4 (C-5); 23,7 (C-8); 22,9 (C-3´´); 20,3 (C-15); 
18,8 (C-6´´); 12,9 (C-16). ESI-HRMS: lý thuyết: C31H43N4O6: 567.31826; tìm thấy: 
567.31820 [M + H]
+
. 
59 
Pyrrolidin-1-yl(3-(4-((((3R,6R,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-
3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)-1H-1,2,3-
triazol-1-yl)phenyl)methanone (62i) 
Chất dầu: sắc ký cột hệ dung môi CH2Cl2: MeOH: Et3N (99: 1: 0,1); 55 %. 
IR (film, v (cm
-1
)): 1690, 1551, 1487, 1452, 1389, 1188, 1102, 1053, 977, 931. 
1
H 
NMR (500 MHz, CDCl3) δ (ppm): 8,03 (s, 1H, H-3´); 7,92 (d, J = 1,0 Hz, 1H, H-
7´); 7,86–7,84 (m, 1H, H-5´); 7,60–7,56 (m, 2H, H-8´, H-9´); 5,45 (s, 1H, H-12); 
5,03 (d, J = 12,5 Hz, 1H, H-1´); 4,98 (d, J = 3,5 Hz, 1H, H-10); 4,78 (d, J = 12,5 Hz, 
1H, H-1´); 3,67 (t, J = 7,0 Hz, 2H, H-1´´); 3,49 (J = 7,0 Hz, 2H, H-1´´); 2,69–2,66 
(m, 1H, H-9); 2,41–2,35 (tt, 1H, J = 14,5, 10,5 Hz, 1H, H-4α); 2,04–1,97 (m, 1H, H-
4β); 1,95–1,86 (m, 4H, H-8α, H-5α, H-2´´); 1,79–1,74 (m, 2H, H-2´´); 1,64–1,60 
(m, 1H, H-7β); 1,50–1,47 (m, 2H, H-8α, H-5β); 1,45 (s, 3H, H-14); 1,35–1,31 (m, 
1H, H-6); 1,28–1,21 (m, 1H, H-5α); 0,94 (overlap, 7H, H-7α, H-15, H-16). 13C 
NMR (125 MHz, CDCl3) δ (ppm): 167,9 (C=O); 145,9 (C-2´); 138,7 (C-6´); 136,9 
(C-9´); 129,8 (C-8´); 127,1 (C-4´); 121,7 (C-7´); 120,7 (C-5´); 119,3 (C-3´); 104,1 
(C-3); 101,8 (C-10); 87,9 (C-12); 81,0 (C-12a); 61,6 (C-1´); 52,4 (C-5a); 49,6 (C-
1´´); 46,3 (C-8a); 37,3 (C-6); 36,3 (C-4); 34,5 (C-7); 30,8 (C-9); 26,3 (C-14); 26,0 
(C-2´´); 24,6 (C-5); 24,3 (C-8); 20,2 (C-15); 12,9 (C-16). ESIHRMS: lý thuyết: 
C29H39N4O6: 539.28696; tìm thấy: 539.28691[M + H]
+
. 
60 
Tổng hợp chất 63 
Một hỗn hợp của 60 (350 mg, 1,08 mmol) và 4-azido-7-chloroquinoline (243 
mg; 1,1 eq), L-ascorbic acid sodium (26 mg, 0,13 mmol) trong CH2Cl2 (10 mL) 
được khuấy ở nhiệt độ phòng trong 10 phút. CuSO4.5H2O (20 mg; 0,066 mmol) sau 
đó được bổ sung vào và phản ứng được khuấy tiếp them 20 giờ ở nhiệt độ phòng. 
Hỗn hợp phản ứng sau đó được pha loãng với CH2Cl2 (15 mL) và chiết với H2O (2 
× 10 mL). Pha hữu cơ được tách ra và làm khan bằng Na2SO4, bốc hơi dung môi 
dưới áp suất giảm. Triazole 63 thu được bằng sắc ký cột sử dụng hệ dung môi 
CH2Cl2: MeOH: Et