Natural products-based insecticidal agents 5. Design, semisynthesis and insecticidal activity of novel 4′-substituted benzenesulfonate derivatives of 4-deoxypodophyllotoxin against Mythimna separata Walker in vivo

Article abstract of DOI:10.1016/j.bmcl.2010.02.108

In an attempt to find the effective phytopesticides, eight novel 4′-substituted benzenesulfonate derivatives of 4-deoxypodophyllotoxin were synthesized and preliminarily tested against the pre-third-instar larvae of Mythimna separata Walker in vivo at the concentration of 1 mg/mL. Among all of the tested analogs, compounds 5a, 5c, 5d, and 5h showed the higher insecticidal activity than 4-deoxypodophyllotoxin. Especially 5a exhibited the most potent insecticidal activity compared with toosendanin, a commercial insecticide derived from Melia azedarach.

Full text of DOI:10.1016/j.bmcl.2010.02.108

Bioorganic & Medicinal Chemistry Letters 20 (2010) 2500–2502
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Natural products-based insecticidal agents 5. Design, semisynthesis and
insecticidal activity of novel 40-substituted benzenesulfonate derivatives
of 4-deoxypodophyllotoxin against Mythimna separata Walker in vivo
*
Hui Xu , Juan-Juan Wang
Laboratory of Pharmaceutical Design and Synthesis, College of Sciences, Northwest A&F University, Yangling 712100, China
a r t i c l e i n f o
a b s t r a c t
In an attempt to find the effective phytopesticides, eight novel 40-substituted benzenesulfonate deriva-
tives of 4-deoxypodophyllotoxin were synthesized and preliminarily tested against the pre-third-instar
larvae of Mythimna separata Walker in vivo at the concentration of 1 mg/mL. Among all of the tested ana-
logs, compounds 5a, 5c, 5d, and 5h showed the higher insecticidal activity than 4-deoxypodophyllotoxin.
Especially 5a exhibited the most potent insecticidal activity compared with toosendanin, a commercial
insecticide derived from Melia azedarach.
Article history:
Received 27 October 2009
Revised 21 January 2010
Accepted 27 February 2010
Available online 11 March 2010
Keywords:
Ó 2010 Elsevier Ltd. All rights reserved.
Podophyllotoxin
4-Deoxypodophyllotoxin
Benzenesulfonate
Semisynthesis
Insecticidal activity
The routine use of a wide variety of synthetic insecticides in
agriculture has now become an accepted practice, however, the
use of these chemicals over the years has resulted in the develop-
ment of resistance in insect pest populations and environmental
problems. Therefore, it is highly desirable to develop the pest man-
agement methods from natural products. Podophyllotoxin (1,
Fig. 1) is naturally occurring aryltetralin lignan, and its derivatives
such as etoposide and teniposide are currently applied in the che-
motherapy for small cell lung cancer, testicular carcinoma, Kaposi’s
sarcoma, and human immunodeficiency virus (HIV).1–3 On the
other hand, compound 1 was also found to possess insecticidal
activity.4–6 More recently, 4b-benzenesulfonamides of podophyllo-
derivatives of 4-deoxypodophyllotoxin (5a–h) were then synthe-
sized by the reaction of 4 with the corresponding substituted ben-
zenesulfonyl chlorides in the presence of triethylamine. The
structures of the target molecules were well characterized by 1H
NMR, MS, HR-MS, optical rotation, and IR.11
The insecticidal activity of compounds 3, 4, and 5a–h against
the pre-third-instar larvae of Mythimna separata Walker was as-
sessed at the concentration of 1 mg/mL by leaf-dipping method.9
Toosendanin, a commercial insecticide derived from Melia azed-
arach, was used as a positive control.
As shown in Table 1, it was found that the corresponding cor-
rected mortality rates caused by these derivatives after 30 d were
higher than those after 10 d and 20 d. For example, the corrected
mortality rate of 5d against M. separata after 10 d was only 3.3%,
after 20 d the corresponding mortality rate was increased to
20.7%, but after 30 d it was sharply increased to 42.9%, which
was 13 times of the mortality rate after 10 d. That is, these com-
pounds, different from those conventional neurotoxic insecticides,
such as organophosphates, carbamates and pyrethroids, showed
delayed insecticidal activity.7–9 Meanwhile, the symptoms of the
tested M. separata were also characterized by the same way as
our previous reports.7–9 For example, the movement of the M. sep-
arata treated by these compounds decreased greatly after 24 h, and
after 48 h some of them were becoming immobilized and loss of
body liquid. Some of the treated M. separata showed moulting dis-
turbances or deformities. For example, the pupation of the larvae
and the adult emergence of M. separata were inhibited by these
toxin,7 -esters of 2-chloropodophyllotoxin (2),8 and 40-aromatic
4a
esters of 4-deoxypodophyllotoxin (3)9 have been designed and
prepared from compound 1 in our research group, and some ana-
logs have displayed more potent insecticidal activity than 1. There-
fore, in this Letter we want to investigate the effect of substituted
benzenesulfonates groups at the C-40 position of 4-deoxypodo-
phyllotoxin on the insecticidal activity.
As shown in Scheme 1, 40-demethyl-4-deoxypodophyllotoxin
(4) was prepared from podophyllotoxin (1) by catalytic hydrogen-
olysis in the presence of 10% palladium/carbon, followed by regio-
selective 40-demethylation of 4-deoxypodophyllotoxin with dry
hydrobromide (3).10 Eight novel 40-substituted benzenesulfonate
* Corresponding author. Tel./fax: +86 29 87091952.
E-mail address: orgxuhui@nwsuaf.edu.cn (H. Xu).
0960-894X/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2010.02.108

H. Xu, J.-J. Wang / Bioorg. Med. Chem. Lett. 20 (2010) 2500–2502
2501
OH
OH
5
8
3
2
O
O
O
O
O
O
4
1
O
O
O
Cl
O
O
O
1'
4'
2'
6'
H3CO
OCH3
H3CO
OCH3
OCH3
H3CO
OCH3
OCH3
OCH3
1
3
2
Figure 1. Chemical structures of podophyllotoxin (1), 2-chloropodophyllotoxin (2), and deoxypodophyllotoxin (3).
OH
O
O
O
O
H2, 10% Pd/C
1) HBr/ ClCH2CH2Cl
O
O
°
95 C, 2 atm
2) BaCO3/H2O/ acetone
O
O
66%
60%
H3CO
OCH3
H3CO
OCH3
OMe
3
OMe
1
O
O
O
O
O
O
RSO2Cl
O
O
Et3N/CH2Cl2
H3CO
OCH3
67% -91%
H3CO
OCH3
O
O
S
R
O
5a-h
OH
4
R
R
R
R
NO2
5c
5a
5b
5e
5f
5g
OMe
NO2
Et
Cl
5d
5h
Cl
Me
Br
Scheme 1.
compounds, therefore, the stage from the larvae to adulthood of M.
separata was prolonged as compared to the control group. More-
over, many larvae of the treated groups molted to abnormal pupae,
which could not reach adulthood and died during the stage of
pupation because they were not able to remove their pupal skin.
Through a comparative study between the insecticidal activity
and the chemical structures of 40-substituted benzenesulfonate
derivatives of 4-deoxypodophyllotoxin (5a–h), some interesting
results were obtained as follows: (1) The methyl group on the 40 po-
sition of 3 was necessary for its insecticidal activity. That is, when the
40-methyl group of 3 was removed to give 4, the corresponding
insecticidal activity of 4 would reduce to some degree. For example,
the corrected mortality rates of 3 and 4 against M. separata after 10,
20, and 30 d were 16.7/10.0%, 20.7/13.8%, and 39.3/21.4%, respec-
tively. (2) The electronic effect of the substituent groups on the 40-
benzenesulfonate0s ring of 4-deoxypodophyllotoxin to insecticidal
activity was not obvious. For example, when the nitro group,
methoxy group, or bromo atom was introduced on the 40-benzene-
sulfonate0s ring of 4-deoxypodophyllotoxin, the insecticidal activity
of the correspondingcompoundswould be increased as compared to
3 (5a 60.7%, 5c 46.4%, 5d 42.9%, and 5h 50.0% vs 3 39.3%); on the con-
trary, when the methyl group, ethyl group, or chlorine atom was
Table 1
Insecticidal activity of 5a–h against Mythimna separata Walker in vivo
Compounds
Corrected mortality rate (%)
20 d
10 d
30 d
5a
5b
5c
5d
5e
5f
5g
5h
26.7 ( 4.7)
16.7 ( 4.7)
33.3 ( 9.4)
3.3 ( 4.7)
10.0 ( 7.4)
3.3 ( 4.7)
13.3 ( 4.7)
20.0 ( 0)
27.6 ( 8.2)
13.8 ( 4.7)
37.9 ( 8.2)
20.7 ( 12.5)
10.3 ( 4.7)
10.3 ( 5.8)
27.6 ( 8.2)
31.0 ( 4.7)
20.7 ( 4.7)
13.8 ( 4.7)
34.5 ( 4.7)
60.7 ( 4.7)
35.7 ( 8.2)
46.4 ( 8.2)
42.9 ( 9.4)
25.0 ( 8.2)
21.4 ( 9.4)
35.7 ( 0)
50.0 ( 8.2)
39.3 ( 4.7)
21.4 ( 4.7)
46.4 ( 8.2)
3
4
16.7 ( 4.7)
10.0 ( 0)
30.0 ( 8.2)
Toosendanin

2502
H. Xu, J.-J. Wang / Bioorg. Med. Chem. Lett. 20 (2010) 2500–2502
1H, H-4), 2.71 (m, 3H, H-2, 3, 4); MS (EI), m/z (%) 398.1 (M+, 100). Compound 4:
introduced on the 40-benzenesulfonate0s ring of 4-deoxypodo-
phyllotoxin, the corresponding insecticidal activity was decreased
as compared to 3 (5e 25.0%, 5f 21.4%, and 5g 35.7% vs 3 39.3%). (3)
Compound 5a bearing the nitro group at the meta position on the
40-benzenesulfonate0s ring of 4-deoxypodophyllotoxin, whose cor-
rected mortality rate against M. separata after 30 d was 60.7%,
showed the most promising and best insecticidal activity as com-
pared to 3 (39.3%) and toosendanin (46.4%). Especially compound
5a exhibited the same potent insecticidal activity as 40-deoxypodo-
phyllotoxin nicotinate or isonicotinate.9
mp 246–248 °C; ½a D20
ꢀ
= ꢁ130 (c 0.4 mg/mL, CHCl3); IR cmꢁ1: 2899, 2824, 1757,
1608, 1478, 1458, 1214, 1105, 922, 769; 1H NMR (400 MHz, CDCl3) d: 6.66 (s,
1H, H-5), 6.51 (s, 1H, H-8), 6.35 (s, 2H, H-20, 60), 5.92 (m, 2H, OCH2O), 5.39 (s,
1H, 40-OH), 4.59 (d, J = 2.4 Hz, 1H, H-1), 4.42 (m, 1H, H-11), 3.88 (m, 1H, H-11),
3.78 (s, 6H, 30,50-OCH3), 3.05 (m, 1H, H-4), 2.71 (m, 3H, H-2, 3, 4); MS (EI), m/z
(%) 383.9 (M+, 100).
11. Spectral data for 5a: yellow solid, mp 115 °C; ½a D20
= ꢁ48 (c 4 mg/mL, CHCl3); IR
ꢀ
cmꢁ1: 2916, 2845, 1769, 1598, 1483, 1462, 1378, 1225, 1126, 929, 705; 1H
NMR (400 MHz, CDCl3) d: 8.89 (s, 1H, H-200), 8.48–8.51 (m, 1H, H-600), 8.30–8.33
(m, 1H, H-400), 7.74 (t, J = 8.0 Hz, 1H, H-500), 6.67 (s, 1H, H-5), 6.50 (s, 1H, H-8),
6.36 (s, 2H, H-20, 60), 5.94 (dd, J = 1.2, 10 Hz, 2H, OCH2O), 4.61 (d, J = 4.8 Hz, 1H,
H-1), 4.46–4.50 (m, 1H, H-11), 3.90–3.95 (m, 1H, H-11), 3.61 (s, 6H, 30,50-
OCH3), 3.05–3.10 (m, 1H, H-4), 2.74–2.81(m, 3H, H-2, 3, 4); HRMS: Calcd for
C27H27N2O11S ([M+NH4]+), 587.1330; found, 587.1326. 5b: white solid, mp
In conclusion, eight novel 40-substituted benzenesulfonate
derivatives of 4-deoxypodophyllotoxin were synthesized and pre-
liminarily tested against the pre-third-instar larvae of M. separata
Walker in vivo at the concentration of 1 mg/mL. Among all of the
tested compounds, analogs 5a, 5c, 5d, and 5h showed the higher
insecticidal activity than 4-deoxypodophyllotoxin. Especially 5a
exhibited the most potent insecticidal activity compared with too-
sendanin, a commercial insecticide derived from M. azedarach.
248–250 °C; ½a 2D0
ꢀ
= ꢁ70 (c 5.3 mg/mL, CHCl3); IR cmꢁ1: 2881, 2838, 1765,
1596, 1484, 1460, 1373, 1227, 1129, 932, 755, 733; 1H NMR (400 MHz, CDCl3)
d: 7.95 (d, J = 8.8 Hz, 2H, H-200, 600), 7.61 (t, J = 8.0 Hz, 1H, H-400), 7.50 (t,
J = 8.0 Hz, 2H, H-300, 500), 6.66 (s, 1H, H-5), 6.50 (s, 1H, H-8), 6.32 (s, 2H, H-20, 60),
5.93 (dd, J = 1.2, 9.6 Hz, 2H, OCH2O), 4.59 (d, J = 4.8 Hz, 1H, H-1), 4.45–4.49 (m,
1H, H-11), 3.90–3.94 (m, 1H, H-11), 3.53 (s, 6H, 30,50-OCH3), 3.04–3.09 (m, 1H,
H-4), 2.68–2.80 (m, 3H, H-2, 3, 4); MS (ESI-TRAP), m/z (%) 525 ([M+1]+, 100);
HRMS: Calcd for C27H28NO9S ([M+NH4]+), 542.1479; found, 542.1469. 5c:
white solid, mp 94–96 °C; ½a D20
ꢀ
= ꢁ47 (c 3.6 mg/mL, CHCl3); IR cmꢁ1: 2915,
2838, 1767, 1595, 1483, 1460, 1367, 1225, 1127, 929, 755; 1H NMR (400 MHz,
CDCl3) d: 7.87 (d, J = 8.8 Hz, 2H, H-200, 600), 6.96 (d, J = 8.8 Hz, 2H, H-300, 500), 6.66
(s, 1H, H-5), 6.50 (s, 1H, H-8), 6.32 (s, 2H, H-20, 60), 5.93 (s, 2H, OCH2O), 4.59 (d,
J = 4.0 Hz, 1H, H-1), 4.45–4.49 (m, 1H, H-11), 3.88–3.94 (m, 1H, H-11), 3.88 (s,
3H, C6H4OCH3), 3.57 (s, 6H, 30,50-OCH3), 3.04–3.09 (m, 1H, H-4), 2.72–2.80 (m,
3H, H-2, 3, 4); MS (ESI-TRAP), m/z (%) 555 ([M+1]+, 100); HRMS: Calcd for
C28H30NO10S ([M+NH4]+), 572.1585; found, 572.1572. 5d: yellow solid, mp 97–
Acknowledgments
This work was financially supported by the Program for New
Century Excellent University Talents, State Education Ministry of
China (NCET-06-0868), the Key Project of Chinese Ministry of Edu-
cation (No. 107105), and the Research Fund for the Doctoral Pro-
gram of Higher Education of China (No. 20070712025).
99 °C; ½a 2D0
ꢀ
= ꢁ58 (c 7 mg/mL, CHCl3); IR cmꢁ1: 2903, 2844, 1769, 1597, 1483,
1462, 1379, 1225, 1127, 929, 752, 709; 1H NMR (400 MHz, CDCl3) d: 8.48 (d,
J = 2.4 Hz, 1H, H-200), 8.09 (dd, J = 2.0, 8.4 Hz, 1H, H-500), 7.73 (d, J = 8.8 Hz, 1H,
H-600), 6.67 (s, 1H, H-5), 6.50 (s, 1H, H-8), 6.36 (s, 2H, H-20, 60), 5.94 (dd, J = 1.2,
10 Hz, 2H, OCH2O), 4.61 (d, J = 4.8 Hz, 1H, H-1), 4.46–4.50 (m, 1H, H-11), 3.91–
3.95 (m, 1H, H-11), 3.62 (s, 6H, 30,50-OCH3), 3.05–3.11 (m, 1H, H-4), 2.65–2.81
(m, 3H, H-2, 3, 4); MS (ESI-TRAP), m/z (%) 604 ([M+1]+, 93); HRMS: Calcd for
C27H26N2O11SCl ([M+NH4]+), 621.0940; found, 621.0943. 5e: white solid, mp
References and notes
1. Xu, H.; Lv, M.; Tian, X. Curr. Med. Chem. 2009, 16, 327.
2. Issell, B. F. Cancer Chemother. Pharmacol. 1982, 7, 73.
114–116 °C; ½a 2D0
ꢀ
= ꢁ57 (c 3.9 mg/mL, CHCl3); IR cmꢁ1: 2909, 2831, 1769,
1597, 1482, 1461, 1374, 1225, 1127, 930, 758; 1H NMR (400 MHz, CDCl3) d:
7.88 (d, J = 7.2 Hz, 2H, H-200, 600), 7.49 (d, J = 8.8 Hz, 2H, H-300, 500), 6.66 (s, 1H, H-
5), 6.49 (s, 1H, H-8), 6.33 (s, 2H, H-20, 60), 5.93 (dd, J = 1.2, 9.6 Hz, 2H, OCH2O),
4.59 (d, J = 4.8 Hz, 1H, H-1), 4.45–4.49 (m, 1H, H-11), 3.90–395 (m, 1H, H-11),
3.56 (s, 6H, 30,50-OCH3), 3.04–3.09 (m, 1H, H-4), 2.65–2.80 (m, 3H, H-2, 3, 4);
MS (ESI-TRAP), m/z (%) 559 ([M+1]+, 61); HRMS: Calcd for C27H27NO9SCl
([M+NH4]+), 576.1090; found, 576.1087. 5f: white solid, mp 97–99 °C;
3. (a) Lee, C. T. L.; Lin, V. C. K.; Zhang, S. X.; Zhu, X. K.; VanVliet, D.; Hu, H.; Beers, S.
A.; Wang, Z. Q.; Cosentino, L. M.; Morris-Natschke, S. L.; Lee, K. H. Bioorg. Med.
Chem. Lett. 1997, 7, 2897; (b) Zhu, X. K.; Guan, J.; Xiao, Z. Y.; Cosentino, L. M.;
Lee, K. H. Bioorg. Med. Chem. 2004, 12, 4267.
4. Kozawa, M.; Baba, K.; Matsuyama, Y.; Kido, T.; Sakai, M.; Takemoto, T. Chem.
Pharm. Bull. 1982, 30, 2885.
5. Inamori, Y.; Kubo, M.; Kato, Y.; Tsujibo, H.; Sakai, M.; Kozawa, M. Chem. Pharm.
Bull. 1986, 34, 2542.
6. Miyazawa, M.; Fukuyama, M.; Yoshio, K.; Kato, T.; Ishikawa, Y. J. Agric. Food
Chem. 1999, 47, 5108.
½
a 2D0
ꢀ
= ꢁ50 (c 4.2 mg/mL, CHCl3); IR cmꢁ1: 2920, 2838, 1769, 1596, 1483,
1460, 1368, 1225, 1127, 929, 755; 1H NMR (400 MHz, CDCl3) d: 7.83 (d,
J = 8.4 Hz, 2H, H-200, 600), 7.30 (d, J = 8.0 Hz, 2H, H-300, 500), 6.66 (s, 1H, H-5), 6.50
(s, 1H, H-8), 6.32 (s, 2H, H-20, 60), 5.93 (dd, J = 1.2, 9.2 Hz, 2H, OCH2O), 4.59 (d,
J = 4.8 Hz, 1H, H-1), 4.45–4.49 (m, 1H, H–11), 3.89–3.94 (m, 1H, H-11), 3.55 (s,
6H, 30,50-OCH3), 3.04–3.09 (m, 1H, H-4), 2.66–2.80 (m, 3H, H-2, 3, 4), 2.45 (s,
3H, C6H4CH3); MS (ESI-TRAP), m/z (%) 539 ([M+1]+, 100); HRMS: Calcd for
C28H30NO9S ([M+NH4]+), 556.1636; found, 556.1644. 5g: white solid, mp 106–
7. Xu, H.; Zhang, L.; Su, B. F.; Zhang, X.; Tian, X. Heterocycles 2009, 77, 293.
8. Xu, H.; Xiao, X. Bioorg. Med. Chem. Lett. 2009, 19, 5415.
9. Xu, H.; Wang, J. J.; Sun, H. J.; Lv, M.; Tian, X.; Yao, X. J.; Zhang, X. J. Agric. Food
Chem. 2009, 57, 7919.
10. The representative procedure for the synthesis of compound 4: A mixture of 10%
palladium/carbon (12.0 g) and podophyllotoxin (1, 16.0 g, 38.6 mmol) in acetic
acid solution (150 mL) was stirred at 95 °C under 2 atm of hydrogen for 5 h.
After filtration to remove the catalyst and evaporation of the solvent, the
residue was purified by silica gel column chromatography to give the crude
product, which was further purified by recrystallization from methanol to
afford 9.8 g (66%) of 3 as a white solid. Then compound 3 (2 g, 50.2 mmol) was
suspended in 1,2-dichloroethane (25 mL) and diethyl ether (2.5 mL) at 0 °C. A
flow of dry hydrobromic acid was passed in the above solution. When the
reaction was complete according to TLC analysis, water (25 mL), acetone
(25 mL) and a little amount of BaCO3 were added to the reaction mixture,
which continued to stir for 0.5 h and extracted by EtOAc. Subsequently, the
combined organic phase was washed by brine, dried over anhydrous Na2SO4,
filtered, concentrated and purified by silica gel column chromatography to give
107 °C; ½a 2D0
ꢀ
= ꢁ60 (c 4.1 mg/mL, CHCl3); IR cmꢁ1: 2917, 1770, 1596, 1483,
1460, 1369, 1225, 1127, 929, 755; 1H NMR (400 MHz, CDCl3) d: 7.85 (d,
J = 8.4 Hz, 2H, H-200, 600), 7.33 (d, J = 8.4 Hz, 2H, H-300, 500), 6.66 (s, 1H, H-5), 6.50
(s, 1H, H-8), 6.32 (s, 2H, H-20, 60), 5.93 (dd, J = 1.2, 9.2 Hz, 2H, OCH2O), 4.59 (d,
J = 4.8 Hz, 1H, H-1), 4.45–4.49 (m, 1H, H-11), 3.90–3.94 (m, 1H, H-11), 3.54 (s,
6H, 30,50-OCH3), 3.04–3.09 (m, 1H, H-4), 2.69–2.80 (m, 5H, H-2, 3, 4,
C6H4CH2CH3), 1.25 (t, J = 7.6 Hz, 3H, C6H4CH2CH3); MS (ESI-TRAP), m/z (%)
553 ([M+1]+, 100); HRMS: Calcd for C29H32NO9S ([M+NH4]+), 570.1792; found,
570.1797. 5h: white solid, mp 96–98 °C; ½a D20
= ꢁ53 (c 3.6 mg/mL, CHCl3); IR
ꢀ
cmꢁ1: 2918, 2854, 1769, 1597, 1483, 1462, 1373, 1225, 1127, 930, 745; 1H
NMR (400 MHz, CDCl3) d: 7.80 (d, J = 8.4 Hz, 2H, H-200, 600), 7.49 (d, J = 8.8 Hz,
2H, H-300, 500), 6.66 (s, 1H, H-5), 6.49 (s, 1H, H-8), 6.32 (s, 2H, H-20, 60), 5.93 (dd,
J = 1.2, 9.6 Hz, 2H, OCH2O), 4.59 (d, J = 4.8 Hz, 1H, H-1), 4.45–4.49 (m, 1H, H-
11), 3.90–3.94 (m, 1H, H-11), 3.56 (s, 6H, 30,50-OCH3), 3.04–3.09 (m, 1H, H-4),
2.65–2.80 (m, 3H, H-2, 3, 4); MS (ESI-TRAP), m/z (%) 603 ([M+1]+, 100); HRMS:
Calcd for C27H27NO9SBr ([M+NH4]+), 620.0584; found, 620.0578.
1.16 g (60%) of 4 as a khaki solid. Compound 3: mp 165–167 °C; ½a D20
= ꢁ116 (c
ꢀ
1 mg/mL, CHCl3); IR cmꢁ1: 2892, 2831, 1763, 1587, 1482, 1457, 1223, 1120,
925, 768; 1H NMR (400 MHz, CDCl3) d: 6.67 (s, 1H, H-5), 6.52 (s, 1H, H-8), 6.34
(s, 2H, H-20, 60), 5.93 (d, J = 8.0 Hz, 2H, OCH2O), 4.60 (s, 1H, H-1), 4.43 (m, 1H, H-
11), 3.89 (m, 1H, H-11), 3.79 (s, 3H, 40-OCH3), 3.75 (s, 6H, 30,50-OCH3), 3.06 (m,