Hemisynthesis and Anticancer Effect of Ferutinin Analogues
167.4; DCI-MS (m/z): 359.2 (MH+). HRMS (DCI) calcd for
22H31O4: 359.2222, found: 359.2221 (MH+).
J = 16 Hz, 1H), 5.44 (br s, 1H), 3.91 (td, J = 2.5 Hz and
J = 12.5 Hz, 1H), 2.31 (br t, 1H), 2.18 (dd, J = 3 Hz and
J = 14.5 Hz, 1H), 2.10 (sept, J = 6.5 Hz, 1H), 1.96 (dd,
J = 6 Hz and J = 14.5 Hz, 1H), 1.93 (dd, J = 8 Hz and
J = 14 Hz, 1H), 1.80–1.83 (m, 1H), 1.76 (s, 3H), 1.66 (d,
J = 10.5 Hz, 1H), 1.55 (td, J = 8 Hz and J = 14 Hz, 1H),
1.42 (dd, J = 7.5 Hz and J = 12.5 Hz, 1H), 1.16 (ddd,
J = 8.5 Hz and J = 12.5 Hz, 1H), 0.97 (s, 3H), 0.92 (d,
J = 7 Hz, 3H), 0.88 (d, J = 7 Hz, 3H); 13C NMR (CDCl3) d
17.6, 18.6, 20.1, 26.5, 31.7, 37.3, 41.0, 41.3, 41.5, 44.0,
56.0, 60.1, 70.7, 86.3, 109,5, 114.7, 115.5, 125.2, 126.8,
123.2, 133.6, 145.6, 146.8, 148.1, 167.5; DCI-MS (m/z):
415.2 (MH+). HRMS (DCI) calcd for C25H35O5: 415.2484,
found: 415.2476 (MH+).
C
(3R, 4S, 8aR)-3-hydroxy-3-isopropyl-6, 8a-dimethyl-1,
2, 3, 3a, 4, 5, 8, 8a-octahydroazulen-4-yl 4-hydroxy-3-
methoxybenzoate (1d’). Starting from jaeschkenadiol
(50 mg, 0.209 mmol) and 4d acid (73.9 mg, 0.293 mmol),
1d’ was obtained (25.6 mg, 60% yield, amorphous foam);
IR (cmÀ1): 3408, 1690, 1596, 1429, 1284, 1103. 1H NMR
(CDCl3) d 7.60 (d, J = 8.5 Hz, 1H), 7.54 (s, 1H), 6.94 (d,
J = 8.5 Hz, 1H), 5.44 (br s, 1H), 3.94 (s, OMe, 3H), 3.91
(td, J = 2.5 Hz and J = 12.5 Hz, 1H), 2.31 (br t, 1H), 2.18
(dd, J = 3 Hz and J = 14.5 Hz, 1H), 2.10 (sept,
J = 6.5 Hz, 1H), 1.96 (dd, J = 6 Hz and J = 14.5 Hz, 1H),
1.93 (dd, J = 8 Hz and J = 14 Hz, 1H), 1.80–1.83 (m,
1H), 1.76 (s, 3H), 1.66 (d, J = 10.5 Hz, 1H), 1.55 (td,
J = 8 Hz and J = 14 Hz, 1H), 1.42 (dd, J = 7.5 Hz and
J = 12.5 Hz, 1H), 1.16 (ddd, J = 8.5 Hz and J = 12.5 Hz,
1H), 0.97 (s, 3H), 0.92 (d, J = 7 Hz, 3H), 0.88 (d,
J = 7 Hz, 3H); 13C NMR (CDCl3) d 17.6, 18.6, 20.2, 26.4,
31.4, 37.0, 40.9, 41.2, 41.4, 44.1, 56.0, 60.1, 71.3, 87.1,
114.2, 111.8, 122.5, 124.2, 125.3, 133.5, 146.3, 150.2,
166.4; DCI-MS (m/z): 387.2 (M-H+). HRMS (DCI) calcd for
C23H31O5: 387.2171, found: 387.2183 (M-H+).
(E)-(3R, 4S, 8aR)- 3-hydroxy-3-isopropyl-6, 8a-
dimethyl-1, 2, 3, 3a, 4, 5, 8, 8a-octahydroazulen-4-yl)-
3-(3, 4 dihydroxyphenyl) acrylate (2e’). Starting from
jaeschkenadiol (50 mg, 0.209 mmol) and 5e acid (73.9 mg,
0.293 mmol), 2e’ was obtained (22.5 mg, 27% yield, green
oil); IR (cmÀ1): 3373, 1682, 1674, 1633, 1601, 1178. 1H
NMR(CDCl3): d 7.74 (d, 15.9 Hz, 1H), 7.21 (d, 1.8 Hz, 1H),
7.06 (dd, J = 1.8 Hz and J = 8.4 Hz, 1H), 6.92 (d, 8.1 Hz,
1H), 6.57 (d, 15.9 Hz, 1H), 5.44 (br s, 1H), 3.91 (td,
J = 2.5 Hz and J = 12.5 Hz, 1H), 2.31 (br t, 1H), 2.18 (dd,
J = 3 Hz and J = 14.5 Hz, 1H), 2.10 (sept, J = 6.5 Hz,
1H), 1.96 (dd, J = 6 Hz and J = 14.5 Hz, 1H), 1.93 (dd,
J = 8 Hz and J = 14 Hz, 1H), 1.80–1.83 (m, 1H), 1.76 (s,
3H), 1.66 (d, J = 10.5 Hz, 1H), 1.55 (td, J = 8 Hz and
J = 14 Hz, 1H), 1.42 (dd, J = 7.5 Hz and J = 12.5 Hz, 1H),
1.16 (ddd, J = 8.5 Hz and J = 12.5 Hz, 1H), 0.97 (s, 3H),
0.92 (d, J = 7 Hz, 3H), 0.88 (d, J = 7 Hz, 3H); 13C NMR
(CDCl3) d 17.7, 18.6, 20.2, 26.3, 31.2, 36.8, 40.9, 41.1,
41.7, 44.3, 60.5, 71.4, 87.8, 114.2, 114.6, 115.0, 122.2,
125.5, 126.8, 133.4, 144.4, 147.0, 147.7, 169.8; DCI-MS
(m/z): 401.2 (MH+). HRMS (DCI) calcd for C24H33O5:
401.2328, found: 401.2342 (MH+).
(E)-(3R, 4S, 8aR)- 3-hydroxy-3-isopropyl-6, 8a-
dimethyl-1, 2, 3, 3a, 4, 5, 8, 8a-octahydroazulen-4-yl
3-(4-hydroxyphenyl) acrylate (2c’). Starting from
jaeschkenadiol (50 mg, 0.209 mmol) and 5c acid (73 mg,
0.293 mmol), 2c’ was obtained (30 mg, 37% yield, amor-
phous foam); IR (cmÀ1): 3408, 1690, 1596, 1429, 1284.
1H NMR(CDCl3) d 7.67 (d, J = 16 Hz, 1H), 7.47 (d,
J = 8.5 Hz, 2H), 6.88 (d, J = 8.5 Hz, 2H), 6.28 (d,
J = 16 Hz, 1H), 5.44 (br s, 1H), 3.91 (td, J = 2.5 Hz and
J = 12.5 Hz, 1H), 2.31 (br t, 1H), 2.18 (dd, J = 3 Hz and
J = 14.5 Hz, 1H), 2.10 (sept, J = 6.5 Hz, 1H), 1.96 (dd,
J = 6 Hz and J = 14.5 Hz, 1H), 1.93 (dd, J = 8 Hz and
J = 14 Hz, 1H), 1.80–1.83 (m, 1H), 1.76 (s, 3H), 1.66 (d,
J = 10.5 Hz, 1H), 1.55 (td, J = 8 Hz and J = 14 Hz, 1H),
1.42 (dd, J = 7.5 Hz and J = 12.5 Hz, 1H), 1.16 (ddd,
J = 8.5 Hz and J = 12.5 Hz, 1H), 0.97 (s, 3H), 0.92 (d,
J = 7 Hz, 3H), 0.88 (d, J = 7 Hz, 3H); 13C NMR (CDCl3) d
17.6, 18.6, 20.1, 26.5, 31.7, 37.3, 41.0, 41.2, 41.4, 44.0,
60.1, 70.8, 86.6, 115.4, 116.0, 125.2, 126.9, 130.2,
133.6, 145.4, 158.1, 167.7; DCI-MS (m/z): 385.2 (MH+).
(E)-(3R, 4S, 8aR)- 3-hydroxy-3-isopropyl-6, 8a-
dimethyl-1, 2, 3, 3a, 4, 5, 8, 8a-octahydroazulen-4-yl
3-(4-hydroxyphenyl) propanoate (3c’). Starting from
jaeschkenadiol (100 mg, 0.420 mmol) and 6c acid
(122 mg, 0.586 mmol), 3c’ was obtained (108 mg, 67%
yield, amorphous foam); IR υmax cmÀ1: 3388, 1712,
1615, 1450, 1150. 1H NMR(CDCl3) d 7.10 (d, J = 8.4 Hz,
2H), 6.79 (d, J = 8.4 Hz, 2H), 5.44 (br s, 1H), 3.91 (td,
J = 2.5 Hz and J = 12.5 Hz, 1H), 2.92 (m, 2H), 2.60 (m,
2H), 2.31 (br t, 1H), 2.18 (dd, J = 3 Hz and J = 14.5 Hz,
1H), 2.10 (sept, J = 6.5 Hz, 1H), 1.96 (dd, J = 6 Hz and
J = 14.5 Hz, 1H), 1.93 (dd, J = 8 Hz and J = 14 Hz, 1H),
1.80–1.83 (m, 1H), 1.76 (s, 3H), 1.66 (d, J = 10.5 Hz, 1H),
1.55 (td, J = 8 Hz and J = 14 Hz, 1H), 1.42 (dd,
J = 7.5 Hz and J = 12.5 Hz, 1H), 1.16 (ddd, J = 8.5 Hz
and J = 12.5 Hz, 1H), 0.97 (s, 3H), 0.92 (d, J = 7 Hz, 3H),
0.88 (d, J = 7 Hz, 3H); 13C NMR (CDCl3) d 17.5, 18.5,
20.0, 26.5, 30.0, 31.8, 37.0, 37.2, 40.9, 41.3, 41.3, 43.9,
59.8, 70.9, 86.5, 115.5, 125.0, 129.4, 132.3, 133.5,
HRMS (DCI) calcd for
385.2386 (MH+).
C24H33O4: 385.2379, found:
(E)-(3R, 4S, 8aR)- 3-hydroxy-3-isopropyl-6, 8a-
dimethyl-1, 2, 3, 3a, 4, 5, 8, 8a-octahydroazulen-4-yl
3-(4-hydroxy-3-methoxyphenyl)
acrylate
(2d’). Starting from jaeschkenadiol (50 mg, 0.209 mmol)
and 5d acid (81.5 mg, 0.293 mmol), 2d’ was obtained
(38.2 mg, 71% yield, amorphous foam); IR (cmÀ1): 3415,
1689, 1629, 1268, 1172. 1H NMR(CDCl3) d 7.65 (d,
J = 16 Hz, 1H), 7.12 (dd, J = 1.5 Hz and J = 8.5 Hz, 1H),
7.06 (d, J = 2 Hz, 1H), 6.96 (d, J = 8.5 Hz, 1H), 6.27 (d,
Chem Biol Drug Des 2016; 87: 382–397
387