Natural products-based insecticidal agents 4. Semisynthesis and insecticidal activity of novel esters of 2-chloropodophyllotoxin against Mythimna separata Walker in vivo

Article abstract of DOI:10.1016/j.bmcl.2009.07.116

By using podophyllotoxin as a lead compound, eight novel esters of 2-chloropodophyllotoxin were designed, semisynthesized, and preliminarily evaluated for their insecticidal activity against the pre-third-instar larvae of Mythimna separata Walker in vivo

Full text of DOI:10.1016/j.bmcl.2009.07.116

Bioorganic & Medicinal Chemistry Letters 19 (2009) 5415–5418
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Natural products-based insecticidal agents 4. Semisynthesis and insecticidal
activity of novel esters of 2-chloropodophyllotoxin against Mythimna separata
Walker in vivo
*
Hui Xu , Xiao Xiao
Laboratory of Pharmaceutical Design and Synthesis, College of Life 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
Article history:
By using podophyllotoxin as a lead compound, eight novel esters of 2-chloropodophyllotoxin were
designed, semisynthesized, and preliminarily evaluated for their insecticidal activity against the pre-
third-instar larvae of Mythimna separata Walker in vivo for the first time. Among all the tested com-
pounds, especially three esters of 2-chloropodophyllotoxin 8a, 8c, and 8g, and one intermediate 6
showed more promising and pronounced insecticidal activity than toosendanin, a commercial insecticide
derived from Melia azedarach.
Received 13 May 2009
Revised 4 July 2009
Accepted 24 July 2009
Available online 28 July 2009
Keywords:
Ó 2009 Elsevier Ltd. All rights reserved.
Podophyllotoxin
2-Chloropodophyllotoxin
Semisynthesis
Insecticidal activity
Podophyllotoxin (1, Fig. 1), one of the well-known naturally
occurring aryltetralin lignans, is extracted as the main component
from the roots and rhizomes of Podophyllum species such as Podo-
phyllum hexandrum and Podophyllum peltatum.1 Its derivatives,
such as etoposide (VP-16, 2), teniposide (VM-26, 3), and etopophos
virus (HIV).3 Recently, we have reported the insecticidal activity
of the podophyllotoxin derivatives and found some compounds
showed more promising insecticidal activity than podophyllo-
toxin.4,5 According to the previous structure–insecticidal activity
relationship, it was found that the trans-lactone and 40-OCH3 moi-
H
OH
3
2
1
O
O
O
R
4
1
O
O
O
HO
O
1
2
2 R = CH , R = H
OH
3
O
1'
4'
O
2'
6'
O
1
2
3 R =
, R = H
S
O
H CO
OCH
3
3
O
1
2
4 R = CH , R = PO(ONa)
OCH
3
2
3
1
H CO
3
OCH
3
2
OR
Figure 1.
(etoposide phosphate, 4), have been used as DNA topoisomerase II
inhibitors in chemotherapy for various types of cancer,2 and they
are also effective in the treatment of human immunodeficiency
eties of podophyllotoxin were essential to maintain the insecticidal
activity.6 Meanwhile, Durst and co-workers described that 2-chlo-
ropodophyllotoxin had significant anticancer activity.7 Based upon
the above results, we want to further study the insecticidal activity
of 2-chloropodophyllotoxin derivatives being the trans-lactone and
40-OCH3 fragments. Therefore, as an important part of our program
* Corresponding author. Tel./fax: +86 29 87091952.
E-mail address: orgxuhui@nwsuaf.edu.cn (H. Xu).
0960-894X/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2009.07.116

5416
H. Xu, X. Xiao / Bioorg. Med. Chem. Lett. 19 (2009) 5415–5418
aimed at the discovery and development of bioactive mole-
cules,4,5,8–12 in this Letter a series of novel esters of 2-chloropodo-
phyllotoxin (8a–8h) were designed, semisynthesized, and
preliminarily evaluated for their insecticidal activity against the
pre-third-instar larvae of Mythimna separata Walker in vivo for
the first time.
A series of novel esters of 2-chloropodophyllotoxin (8a–8h)
were synthesized as shown in Scheme 1. Starting from podophyl-
lotoxin (1), the 4-OH group of 1 was firstly protected by a tetrahy-
dropyranyl (THP) group in the presence of phosphorus oxychloride
and dihydropyran (DHP) to give 4-O-tetrahydropyranylpodo-
phyllotoxin (5).13 Then 2-chloro-4-O-tetrahydropyranylpodo-
phyllotoxin (6) was obtained by treatment of 5 with lithium
diisopropylamide (LDA) at ꢀ78 °C in dry THF, and followed by ster-
eoselective reaction with hexachloroethane. Subsequently, hydro-
lysis of the THP group of 6 to afford 2-chloropodophyllotoxin
(7).7 Finally, eight novel esters of 2-chloropodophyllotoxin (8a–
8h) were obtained by reaction of 7 with the corresponding aro-
matic acids in the presence of diisopropylcarbodiimide (DIC) and
4-dimethylaminopyridine (DMAP). The structures of the com-
pounds were well characterized by 1H NMR, HRMS, MS, optical
rotation, and IR.14
In order to obtain precise three-dimensional structural informa-
tion and absolute configuration of 8a–8h, compound 8h was
recrystallized by slow evaporation from methanol and its single-
crystal structure was determined by X-ray crystallography as illus-
trated in Figure 2.15 It was clearly demonstrated that the 2-chloro
and the 4-ester groups of 8h adopted the b- and
a-configuration,
respectively.
The insecticidal activity of compounds 5–7 and 8a–8h against
the pre-third-instar larvae of M. separata in vivo was screened by
the leaf-dipping method at the concentration of 1 mg/mL.4 Podo-
phyllotoxin phenylacetate (9),16 and toosendanin, a commercial
insecticide derived from Melia azedarach, were used as positive
controls.
Figure 2. The X-ray crystallography of compound 8h.
those after 10 and 20 d. For example, the corrected mortality rate
of 8a against M. separata after 10 d was only 10.7%, after 20 d the
corresponding mortality rate was increased to 32.1%, but after
35 d the corresponding mortality rate was rapidly increased to
70.4%, which was nearly seven times of the mortality rate after
As indicated in Table 1, the corresponding corrected mortality
rates caused by these compounds after 35 d were far higher than
O
O
O
O
O
O
Cl C CCl
3
O
3
O
LDA/THF
DHP/POCl
O
3
O
1
-
+
o
O Li
-78 C
O
H CO
OCH
3
3
H CO
3
OCH
3
OCH
3
OCH
3
5
O
O
O
OH
R
O
O
O
O
O
O
O
O
conc. HCl/ THF
(v/v:1/9)
O
RCO H/DIC/DMAP
2
Cl
Cl
O
O
O
Cl
O
H CO
3
OCH
3
H CO
OCH
3
3
H CO
3
OCH
3
OCH
OCH
3
3
OCH
3
6
7
8a-h
Scheme 1.

H. Xu, X. Xiao / Bioorg. Med. Chem. Lett. 19 (2009) 5415–5418
5417
Table 1
trol group. Moreover, 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.
Insecticidal activity of novel esters of 2-chloropodophyllotoxin (8a–8h) against
Mythimna separata Walker in vivo
O
Some preliminary structure–insecticidal activity relationships
on the 2-chloropodophyllotoxin derivatives were also investigated.
R
O
O
O
O
As shown in Table 1, when
a-naphthylacetyl, 3-nitrobenzoyl, or
phenylacetyl group was introducedon the C-4 position of 2-chlorop-
odophyllotoxin, the corresponding esters 8a, 8c, and 8g showed
more potent insecticidal activity than toosendanin. For example,
the final mortality rates of 8a, 8c, and 8g were 70.4%, 63.0%, and
63.0%, respectively, while the final mortality rate of toosendanin
was 51.9%. However, when 3,5-dinitrobenzoyl, 4-methylbenzoyl,
3-methylbenzoyl, 2-chlorobenzoyl, or 3-chlorobenzoyl group was
introduced on the C-4 position of 2-chloropodophyllotoxin, the final
mortality rates of the corresponding esters 8b, 8d, 8e, 8f, and 8h
were 644.4%, which were less potent than toosendanin. Interest-
ingly, 2-chloro-4-O-tetrahydropyranylpodophyllotoxin (6), an
intermediate of 8a–8h, alsoexhibited morepotentinsecticidalactiv-
ity than toosendanin (66.7% vs 51.9%), and this encouraging result
will prompt us to further study the ether derivatives of 2-chloropod-
ophyllotoxin as the insecticidal agent in future. Meanwhile, it was
also found that the substituents effect on the C-4 position of 2-chlo-
ropodophyllotoxin derivatives was very important for their insecti-
cidal activity: (1) When some substituents were introduced on the
C-4 position of 2-chloropodophyllotoxin, the corresponding com-
pounds usually showed more potent insecticidal activity than the
podophyllotoxin ones. For example, 2-chloro-4-O-tetrahydropyra-
nylpodophyllotoxin (6) exhibited more potent insecticidal activity
than 4-O-tetrahydropyranylpodophyllotoxin (5) (66.7% vs 51.9%),
and 2-chloropodophyllotoxin phenylacetate (8g) showed more po-
tent insecticidal activity than the corresponding podophyllotoxin
phenylacetate (9) (63.0% vs 51.9%). (2) When there was no substitu-
ent introduced on the C-4 position of 2-chloropodophyllotoxin, the
corresponding compound showed less potent insecticidal activity
than podophyllotoxin (37.0% for 7 vs 44.4% for 1). Consequently, in
combination of our previous results that introducing 4b-benzene-
sulfonamide substituents on the C-4 position of podophyllotoxin
could lead to more potent compounds,5 some 4b-benzenesulfon-
amide-2-chloropodophyllotoxin derivatives will be synthesized
and studied in our laboratory.
Cl
O
H CO
OCH
3
3
OCH
3
8a-h
Compounds
R
Corrected mortality rate (%)
10 d
20 d
35 d
1
5
6
7
/
/
/
/
17.9 ( 17.0)
10.7 ( 9.4)
23.3 ( 12.5)
7.14 ( 4.7)
17.9 ( 17.0)
14.3 ( 14.1)
33.3 ( 4.7)
17.9 ( 12.5)
44.4 ( 12.5)
51.9 ( 12.5)
66.7 ( 4.7)
37.0 ( 9.4)
H C
2
8a
8b
10.7 ( 12.5)
10.7 ( 9.4)
32.1 ( 4.7)
70.4 ( 4.7)
O N
2
25.0 ( 14.1)
44.4 ( 16.3)
O N
2
O N
2
8c
8d
8e
8f
28.6 ( 12.5)
10.7 ( 12.5)
3.6 ( 8.2)
50.0 ( 4.7)
21.4 ( 12.5)
3.6 ( 8.2)
63.0 ( 4.7)
40.7 ( 9.4)
40.7 ( 17.0)
44.4 ( 14.1)
63.0 ( 12.5)
40.7 ( 12.5)
Me
Me
In conclusion, eight novel esters of 2-chloropodophyllotoxin
(8a–8h) were designed, semisynthesized, and evaluated for their
insecticidal activity against the pre-third-instar larvae of M. separa-
ta in vivo at the concentration of 1 mg/mL. Among all the tested
compounds, especially three esters of 2-chloropodophyllotoxin
8a, 8c, and 8g, and one intermediate 6 exhibited the more promis-
ing and pronounced insecticidal activity than toosendanin, a com-
mercial insecticide derived from M. azedarach.
10.7 ( 4.7)
28.6 ( 9.4)
7.1 ( 4.7)
21.4 ( 9.4)
32.14 ( 12.5)
14.3 ( 8.2)
Cl
8g
8h
CH
Cl
2
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).
9
/
/
3.6 ( 0)
25.0 ( 0)
17.9 ( 12.5)
35.7 ( 8.2)
51.9 ( 9.4)
51.9 ( 12.5)
Toosendanin
10 d. That is, these compounds, different from those conventional
neurotoxic insecticides, such as organophosphates, carbamates,
and pyrethroids, showed delayed insecticidal activity.4,5 Mean-
while, the symptoms of the tested M. separata were also character-
ized as the same as our previous reports.4,5 For example, the
pupation of the larvae and the adult emergence of M. separata were
inhibited by these compounds, therefore, the stage from the larvae
to adulthood of M. separata was prolonged as compared to the con-
References and notes
1. Lin, H. W.; Kwok, K. H.; Doran, P. M. Biotechnol. Prog. 2003, 19, 1417.
2. Issell, B. F. Cancer Chemother. Pharmacol. 1982, 7, 73.
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.

5418
H. Xu, X. Xiao / Bioorg. Med. Chem. Lett. 19 (2009) 5415–5418
4. Xu, H.; Zhang, X.; Tian, X.; Lu, M.; Wang, Y. G. Chem. Pharm. Bull. 2002, 50, 399.
5. Xu, H.; Zhang, L.; Su, B. F.; Zhang, X.; Tian, X. Heterocycles 2009, 77, 293.
6. Gao, R.; Gao, C. F.; Tian, X.; Yu, X. Y.; Di, X. D.; Xiao, H.; Zhang, X. Pest. Manag.
Sci. 2004, 60, 1131.
7. Glinski, M. B.; Freed, J. C.; Durst, T. J. Org. Chem. 1987, 52, 2749.
8. Xu, H.; Jian, K. Z.; Guan, Q.; Ye, F.; Lv, M. Chem. Pharm. Bull. 2007, 55, 1755.
9. Xu, H.; Liu, W. Q.; Fan, L. L.; Chen, Y.; Yang, L. M.; Lv, L.; Zheng, Y. T. Chem.
Pharm. Bull. 2008, 56, 720.
4.63 (m, 1H, H-11), 4.44 (m, 1H, H-11), 3.71(s, 9H, 30,40,50-OCH3), 3.23 (m, 1H,
H-3); ESI-MS m/z: 589 ([M+Na]+, 8), 591 ([M+Na]+, 3); HRMS: Anal. Calcd for
C30H27KClO9 ([M+K]+): 605.0975. Found: 605.0987. Compound 8e: White solid,
mp 116—119 °C; ½a D20
ꢁ
¼ ꢀ128 (c 0.33 mg/mL, CHCl3); IR cmꢀ1: 2931, 2821,
1786, 1735, 1588, 1503, 1484, 1458, 1378, 1237, 1124, 1037, 934, 775, 721; 1H
NMR (400 MHz, CDCl3) d: 7.83 (s, 2H, H-200, 600), 7.43 (d, J = 7.2 Hz, 1H, H-500),
7.36 (m, J = 8.0 Hz, 1H, H-400), 6.91 (s, 1H, H-5), 6.60 (s, 1H, H-8), 6.50 (s, 2H, H-
20, 60), 6.21 (d, J = 8.8 Hz, 1H, H-4), 6.00 (m, 2H, OCH2O), 4.83 (s, 1H, H-1), 4.61
(m, 1H, H-11), 4.43 (m, 1H, H-11), 3.80 (s, 9H, 30,40,50-OCH3), 3.26 (m, 1H, H-3),
2.41 (s, 3H, 300-CH3); ESI-MS m/z: 589 ([M+Na]+, 100), 591 ([M+Na]+, 38);
HRMS: Anal. Calcd for C30H27NaClO9 ([M+Na]+): 589.1236. Found: 589.1229.
10. Xu, H.; Fan, L. L. Chem. Pharm. Bull. 2008, 56, 1496.
11. Dai, H. L.; Liu, W. Q.; Xu, H.; Yang, L. M.; Lv, M.; Zheng, Y. T. Chem. Pharm. Bull.
2009, 57, 84.
12. Xu, H.; Lv, M.; Tian, X. Curr. Med. Chem. 2009, 16, 327.
13. Gensler, W. J.; Gatsonis, C. D. J. Org. Chem. 1966, 31, 4004.
Compound 8f: White solid, mp 202—205 °C; ½ ꢁ ¼ ꢀ121 (c 0.30 mg/mL,
a 2D0
CHCl3); IR cmꢀ1: 2929, 2831, 1781, 1731, 1590, 1502, 1482, 1454, 1380, 1235,
1122, 1032, 925, 749; 1H NMR (400 MHz, CDCl3) d: 7.85 (d, J = 8.0 Hz, 1H, H-
600), 7.49 (m, 2H, H-300, 500), 7.35 (m, 1H, H-400), 6.94 (s, 1H, H-5), 6.58 (s, 1H, H-
8), 6.47 (s, 2H, H-20, 60), 6.28 (d, J = 9.2 Hz, 1H, H-4), 6.00 (m, 2H, OCH2O), 4.82
(s, 1H, H-1), 4.63 (m, 1H, H-11), 4.49 (m, 1H, H-11), 3.74(s, 3H, 40-OCH3), 3.68(s,
6H, 30,50-OCH3), 3.30(m, 1H, H-3); ESI-MS m/z: 609 ([M+Na]+, 100), 611
([M+Na]+, 75), 613 ([M+Na]+, 16); HRMS: Anal. Calcd for C29H24NaCl2O9
([M+Na]+): 609.0690. Found: 609.0689. Compound 8g: White solid, mp 88–
14. Spectral data for 8a: White solid, mp 200–203 °C; ½a D20
¼ ꢀ147 (c 0.56 mg/mL,
ꢁ
CHCl3); IR cmꢀ1: 2919, 1776, 1736, 1596, 1505, 1484, 1459, 1379, 1236, 1127,
1038, 937, 753; 1H NMR (400 MHz, CDCl3) d: 7.98 (d, J = 8.0 Hz, 1H,
naphthalene ring), 7.88 (d, J = 7.2 Hz, 1H, naphthalene ring), 7.82 (dd, J = 2.8,
6.8 Hz, 1H, naphthalene ring), 7.53 (m, 2H, naphthalene ring), 7.41 (m, 2H,
naphthalene ring), 6.54 (s, 1H, H-5), 6.48 (s, 1H, H-8), 6.32 (s, 2H, H-20, 60), 5.97
(m, 3H, H-4 and OCH2O), 4.71 (s, 1H, H-1), 4.35 (m, 1H, H-11), 4.19 (s, 2H,
CH2C10H7), 4.05 (m, 1H, H-11), 3.78 (s, 3H, 40-OCH3), 3.63 (s, 6H, 30,50-OCH3),
2.93 (m, 1H, H-3); ESI-MS m/z: 639 ([M+Na]+, 78), 641 ([M+Na]+, 33); HRMS:
Anal. Calcd for C35H31O9NaCl ([M+Na]+): 639.1392. Found: 639.1396.
91 °C; ½a 2D0
ꢁ
¼ ꢀ150 (c 0.54 mg/mL, CHCl3); IR cmꢀ1: 2923, 2831, 1780,1735,
1589, 1503, 1483, 1457, 1378, 1235, 1124, 1037, 935, 756; 1H NMR (400 MHz,
CDCl3) d: 7.36–7.26 (m, 5H, H-200, 300, 400, 500, 600), 6.68 (s, 1H, H-5), 6.52 (s, 1H, H-
8), 6.39 (s, 2H, H-20, 60), 5.98 (m, 3H, H-4 and OCH2O), 4.75 (s, 1H, H-1), 4.41 (m,
1H, H-11), 4.19 (m, 1H, H-11), 3.81–3.67(s, 11H, 30, 40, 50-OCH3 and C6H5CH2),
3.03 (m, 1H, H-3); ESI-MS m/z: 589 ([M+Na]+, 100), 591 ([M+Na]+, 37); HRMS:
Anal. Calcd for C30H27NaClO9 ([M+Na]+): 589.1236. Found: 589.1225.
Compound 8b: Yellow solid, mp 142–145 °C; ½ ꢁ ¼ ꢀ90 (c 0.26 mg/mL,
a 2D0
CHCl3); IR cmꢀ1: 2923, 2845, 1787, 1732, 1590, 1493, 1464, 1337, 1245, 1119,
1041, 927, 781, 721; 1H NMR (400 MHz, CDCl3) d: 9.30 (s, 1H, H-400), 9.15 (s, 2H,
H-200, 600), 6.82 (s, 1H, H-5), 6.64 (s, 1H, H-8), 6.50 (s, 2H, H-20, 60), 6.35 (d,
J = 8.8 Hz, 1H, H-4), 6.04 (m, 2H, OCH2O), 4.86 (s, 1H, H-1), 4.62 (m, 1H, H-11),
4.41 (m, 1H, H-11), 3.75 (s, 9H, 30,40,50-OCH3), 3.31 (m, 1H, H-3); ESI-MS m/z:
665 ([M+Na]+, 20), 667 ([M+Na]+, 9); HRMS: Anal. Calcd for C29H23N2O13NaCl
([M+Na]+): 665.0781. Found: 665.0776. Compound 8c: Yellow solid, mp 96—
Compound 8h: White solid, mp 82–84 °C; ½a D20
¼ ꢀ99 (c 0.71 mg/mL, CHCl3);
ꢁ
IR cmꢀ1: 2934, 2831, 1783, 1722, 1589, 1504, 1484, 1459, 1380, 1239, 1123,
1
1036, 933, 748; H NMR (400 MHz, CDCl3) d: 7.98 (s, 1H, H-200), 7.93 (d,
J = 8.0 Hz, 1H, H-600), 7.60 (d, J = 7.6 Hz, 1H, H-400), 7.42 (m, 1H, H-500), 6.88 (s,
1H, H-5), 6.60 (s, 1H, H-8), 6.49 (s, 2H, H-20, 60), 6.29 (d, J = 9.2 Hz, 1H, H-4),
6.01 (m, 2H, OCH2O), 4.83 (s, 1H, H-1), 4.61 (m, 1H, H-11), 4.42 (m, 1H, H-11),
3.71(s, 9H, 30,40,50-OCH3), 3.25 (m, 1H, H-3); ESI-MS m/z: 609 ([M+Na]+, 100),
611 ([M+Na]+, 64), 613 ([M+Na]+, 13); HRMS: Anal. Calcd for C29H24O9NaCl2
([M+Na]+): 609.0690. Found: 609.0685.
98 °C; ½a 2D0
ꢁ
¼ ꢀ103 (c 0.38 mg/mL, CHCl3); IR cmꢀ1: 2936, 2831, 1786, 1726,
1588, 1532, 1504, 1484, 1459, 1380, 1237, 1123, 1036, 932, 772, 718; 1H NMR
(400 MHz, CDCl3) d: 8.82 (s, 1H, H-200), 8.40 (d, J = 7.6 Hz, 2H, H-400, 600), 7.72 (m,
J = 8.0 Hz,1H, H-500), 6.86 (s, 1H, H-5), 6.62 (s, 1H, H-8), 6.50 (s, 2H, H-20, 60),
6.28 (d, J = 9.2 Hz, 1H, H-4), 6.03 (m, 2H, OCH2O), 4.85 (s, 1H, H-1), 4.60 (m, 1H,
H-11), 4.42 (m, 1H, H-11), 3.80(s, 9H, 30,40,50-OCH3), 3.24 (m, 1H, H-3); ESI-MS
m/z: 620 ([M+Na]+, 100), 622 ([M+Na]+, 42); HRMS: Anal. Calcd for
C29H28ClN2O11 ([M+NH4]+): 615.1376. Found: 615.1370. Compound 8d:
15. Crystallographic data (excluding structure factors) for the structure of 8h in
this paper has been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC 738791. Copies of the data
can be obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: +44 (0)1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk].
White solid, mp 92–94 °C;
½
a 2D0
ꢁ
¼ ꢀ108 (c 0.36 mg/mL, CHCl3); IR cmꢀ1
:
2917, 2831, 1784, 1720, 1588, 1504, 1485, 1455, 1380, 1239, 1122, 1101, 1034,
929,752; 1H NMR (400 MHz, CDCl3) d: 7.91 (d, J = 8.0 Hz,2H, H-200, 600), 7.26 (d,
J = 2.8 Hz,5H, H-300, 500 and 400-CH3), 6.91 (s, 1H, H-5), 6.59 (s, 1H, H-8), 6.49 (s,
2H, H-20, 60), 6.18 (d, J = 9.2 Hz, 1H, H-4), 6.00 (m, 2H, OCH2O), 4.83 (s, 1H, H-1),
16. Lopez-Perez, J. L.; del Olmo, E.; de Pascual-Teresa, B.; Abad, A.; San Feliciano, A.
Bioorg. Med. Chem. Lett. 2004, 14, 1283.