Journal of Agricultural and Food Chemistry
Article
Scheme 1. Synthetic Approach for 2α-Chloropicropodophyllotoxin Derivatives (5a−c) and 2β-Chloropodophyllotoxin
Derivatives (5a′−c′)
2.96−2.97 (m, 1H, H-3), 2.35−2.42 (m, 2H, CH3CH2), 1.20 (t, J = 7.6
Hz, 3H, CH3CH2); 13C NMR (100 MHz, CDCl3) δ 174.2, 171.9,
152.1, 150.0, 149.2, 148.2, 142.8, 132.2, 130.7, 124.2, 122.1, 108.8,
108.6, 108.5, 101.7, 74.9, 73.1, 66.8, 61.1, 61.1, 56.2, 49.4, 44.7, 27.5,
9.0; HRMS m/z calcd for C25H24O9Cl2Na ([M + Na]+) 561.0689,
found 561.0691.
OCHH3), 3.76 (s, 2H, PhCH2), 3.31 (dd, J = 7.2, 3.6 Hz, 1H, H-3);
13C NMR (100 MHz, CDCl3) δ 172.7, 171.6, 149.2, 148.9, 148.1,
147.6, 147.3, 133.2, 133.1, 129.2, 128.8, 127.6, 127.5, 127.5, 125.8,
125.5, 107.7, 105.8, 101.4, 71.6, 71.1, 64.9, 61.3, 61.2, 61.1, 49.0, 44.1,
41.5; HRMS m/z calcd for C30H25O9Cl3Na ([M + Na]+) 657.0456,
found 657.0424.
Data for 6c: yield 77%; white solid; mp = 79−80 °C; [α]19D = −66
Data for 8a: yield 95%; white solid; mp = 176−178 °C; [α]20
=
D
1
1
(c 3.6 mg/mL, CHCl3); H NMR (400 MHz, CDCl3) δ 7.27−7.39
−94 (c 3.4 mg/mL, CHCl3); H NMR (400 MHz, CDCl3) δ 6.71 (s,
1H, H-5), 6.63 (s, 1H, H-8), 6.60 (s, 1H, H-6′), 5.93−5.95 (m, 3H,
OCH2O, H-4), 5.59 (s, 1H, H-1), 4.80−4.81 (m, 2H, H-11), 3.92 (s,
3H, 3′-OCHH3), 3.88 (s, 3H, 5′-OCHH3), 3.76 (s, 3H, 4′-OCHH3),
2.97 (dd, J = 5.2, 2.8 Hz, 1H, H-3), 2.15 (s, 3H, COCH3); 13C NMR
(100 MHz, CDCl3) δ 171.9, 170.6, 152.7, 150.9, 149.2, 148.2, 142.6,
133.9, 130.9, 123.9, 113.7, 108.8, 108.7, 108.6, 101.7, 75.1, 73.1, 66.8,
61.1, 61.0, 56.2, 49.4, 47.3, 21.0; HRMS m/z calcd for
C24H22O9ClBrNa ([M + Na]+) 591.0028, found 591.0028.
(m, 5H), 6.67 (s, 1H, H-5), 6.57 (s, 1H, H-8), 6.51 (s, 1H, H-6′), 5.93
(d, J = 1.2 Hz, 2H, OCH2O), 5.89 (d, J = 3.2 Hz, 1H, H-4), 5.50 (s,
1H, H-1), 4.77−4.78 (m, 2H, H-11), 3.93 (s, 3H, 3′-OCHH3), 3.89 (s,
3H, 5′-OCHH3), 3.75 (s, 3H, 4′-OCHH3), 3.67 (d, J = 6.8 Hz, 2H,
PhCH2), 2.99−3.00 (m, 1H, H-3); 13C NMR (100 MHz, CDCl3) δ
171.8, 171.6, 152.0, 150.0, 149.2, 148.2, 142.8, 132.6, 132.1, 130.6,
129.0, 128.9, 127.7, 123.9, 122.1, 108.7, 108.6, 108.4, 101.7, 75.5, 72.9,
66.7, 61.1, 61.1, 56.3, 49.2, 44.6, 41.1; HRMS m/z calcd for
C30H26O9Cl2Na ([M + Na]+) 623.0846, found 623.0849.
Data for 8b: yield 93%; white solid; mp = 169−170 °C; [α]20
=
D
Data for 7a: yield 90%; white solid; mp = 92−93 °C; [α]20D = −86
1
−83 (c 3.2 mg/mL, CHCl3); H NMR (400 MHz, CDCl3) δ 6.71 (s,
1H, H-5), 6.62 (s, 1H, H-8), 6.60 (s, 1H, H-6′), 5.93−5.94 (m, 3H,
OCH2O, H-4), 5.59 (s, 1H, H-1), 4.80−4.81 (m, 2H, H-11), 3.92 (s,
3H, 3′-OCHH3), 3.88 (s, 3H, 5′-OCHH3), 3.75 (s, 3H, 4′-OCHH3),
2.96−2.99 (m, 1H, H-3), 2.35 (q, J = 7.6 Hz, 2H, COCH2CH3), 1.20
(t, J = 7.6 Hz, 3H, COCH2CH3); 13C NMR (100 MHz, CDCl3) δ
174.2, 171.9, 152.7, 150.9, 149.2, 148.2, 142.7, 134.0, 130.8, 124.1,
113.7, 108.9, 108.7, 108.5, 101.7, 74.8, 73.1, 66.8, 61.1, 61.0, 56.2, 49.4,
47.2, 27.5, 9.0; HRMS m/z calcd for C25H24O9ClBrNa ([M + Na]+)
605.0184, found 605.0169.
1
(c 3.3 mg/mL, CHCl3); H NMR (400 MHz, CDCl3) δ 6.51 (s, 1H,
H-5), 6.23 (s, 1H, H-8), 6.07 (s, 1H, H-1), 5.92−5.93 (m, 3H,
OCH2O, H-4), 4.76−4.78 (m, 1H, H-11), 4.57−4.59 (m, 1H, H-11),
3.98 (s, 3H, 3′-OCHH3), 3.96 (s, 3H, 5′-OCHH3), 3.83 (s, 3H, 4′-
OCHH3), 3.39−3.41 (m, 1H, H-3), 2.24 (s, 3H, COCH3); 13C NMR
(100 MHz, CDCl3) δ 172.8, 171.1, 149.3, 148.9, 148.1, 147.6, 147.4,
133.3, 127.5, 125.9, 125.5, 107.8, 105.7, 101.5, 71.2, 70.9, 64.9, 61.3,
61.3, 61.2, 48.9, 44.1, 21.1; HRMS m/z calcd for C24H21O9Cl3Na ([M
+ Na]+) 581.0143, found 581.0150.
Data for 7b: yield 61%; white solid; mp = 84−86 °C; [α]20
=
D
Data for 8c: yield 98%; white solid; mp = 88−90 °C; [α]20D = −68
−107 (c 2.8 mg/mL, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.49 (s,
1H, H-5), 6.23 (s, 1H, H-8), 6.07 (s, 1H, H-1), 5.90−5.93 (m, 3H,
OCH2O, H-4), 4.75 (dd, J = 7.2, 3.2 Hz, 1H, H-11), 4.58 (d, J = 7.6
Hz, 1H, H-11), 3.98 (s, 3H, 3′-OCHH3), 3.96 (s, 3H, 5′-OCHH3),
3.83 (s, 3H, 4′-OCHH3), 3.38 (dd, J = 5.6, 2.8 Hz, 1H, H-3), 2.49−
1
(c 3.6 mg/mL, CHCl3); H NMR (400 MHz, CDCl3) δ 7.28−7.39
(m, 5H), 6.70 (s, 1H, H-5), 6.59 (s, 1H, H-8), 6.51 (s, 1H, H-6′), 5.94
(d, J = 0.8 Hz, 2H, OCH2O), 5.88 (d, J = 3.2 Hz, 1H, H-4), 5.58 (s,
1H, H-1), 4.78−4.79 (m, 2H, H-11), 3.92 (s, 3H, 3′-OCHH3), 3.88 (s,
3H, 5′-OCHH3), 3.75 (s, 3H, 4′-OCHH3), 3.67 (d, J = 7.2 Hz, 2H,
PhCH2), 2.99 (dd, J = 5.2, 3.2 Hz, 1H, H-3); 13C NMR (100 MHz,
CDCl3) δ 171.8, 171.6, 152.7, 151.0, 149.2, 148.2, 142.7, 133.9, 132.6,
130.8, 129.0, 128.9, 127.7, 123.8, 113.8, 108.9, 108.6, 108.3, 101.7,
75.4, 72.9, 66.8, 61.09, 61.01, 56.3, 49.3, 47.2, 41.1; HRMS m/z calcd
for C30H26O9ClBrNa ([M + Na]+) 667.0341, found 667.0320.
Biological Assay. On the basis of the leaf-dipping method,30 the
b i o l o g i c a l a c t i v i t y o f 2 α - c h l o r o - 2 ′ ( 2 ′ , 6 ′ ) - ( d i ) -
halogenopicropodophyllotoxin esters (6a−k, 7a−i, and 8a−h) was
evaluated as the mortality rate values against Mythimna separata
Walker. For each compound, 30 pre-third-instar larvae (10 larvae per
2.52 (m, 2H, COCH2CH3), 1.23 (t, J = 6.0 Hz, 3H, COCH2CH3); 13
C
NMR (100 MHz, CDCl3) δ 174.4, 172.8, 149.3, 149.0, 148.1, 147.6,
147.4, 133.3, 127.5, 126.1, 125.5, 107.8, 105.8, 101.4, 71.3, 70.9, 65.0,
61.3, 61.2, 61.1, 49.1, 44.1, 27.7, 9.1; HRMS m/z calcd for
C25H23O9Cl3Na ([M + Na]+) 595.0299, found 595.0300.
Data for 7c: yield 71%; white solid; mp = 78−80 °C; [α]20D = −95
1
(c 2.8 mg/mL, CHCl3); H NMR (400 MHz, CDCl3) δ 7.31−7.38
(m, 5H), 6.34 (s, 1H, H-5), 6.21 (s, 1H, H-8), 6.05 (s, 1H, H-1), 5.88
(dd, J = 10.0, 1.2 Hz, 2H, OCH2O), 5.86 (d, J = 7.2 Hz, 1H, H-4),
4.65 (dd, J = 9.2, 4.0 Hz, 1H, H-11), 4.46 (d, J = 9.6 Hz, 1H, H-11),
3.97 (s, 3H, 3′-OCHH3), 3.95 (s, 3H, 5′-OCHH3), 3.83 (s, 3H, 4′-
3728
dx.doi.org/10.1021/jf405316w | J. Agric. Food Chem. 2014, 62, 3726−3733