Synthesis and crystal structure of a depside derivative 2-(2-Methoxy-2-oxoethyl)phenyl 2-(3,4-Dimethoxyphenyl)acetate

Article abstract of DOI:10.1007/s10870-009-9622-0

A depside derivative, 2-(2-methoxy-2-oxoethyl)phenyl 2-(3,4- dimethoxyphenyl)acetate (3), was synthesized through a facile approach in high yields. Its structure was confirmed by ¹H NMR, ¹³C NMR, ESI mass spectra, elemental analyses and X-ray single crystal diffraction study. Crystal structure analysis revealed that compound 3 crystallized in the monoclinic, space group P2₁/c with the following unit cell parameters: a = 10.173(2) A, b = 10.459(2) A, c = 16.516(3) A, α = 90°, β = 102.30(3)°, γ = 90°, V = 1717.0(6) A³, Z = 4.

Full text of DOI:10.1007/s10870-009-9622-0

J Chem Crystallogr (2009) 39:927–930
DOI 10.1007/s10870-009-9622-0
COMMUNICATION
Synthesis and Crystal Structure of a Depside Derivative
2-(2-Methoxy-2-oxoethyl)phenyl 2-(3,4-Dimethoxyphenyl)acetate
Peng-Cheng Lv Æ Kai-Rui Wang Æ Wen-Jun Mao Æ
Rui-Qin Fang Æ Jin Chen Æ Jing Xiong Æ Hai-Liang Zhu
Received: 5 May 2009 / Accepted: 21 August 2009 / Published online: 3 September 2009
Ó Springer Science+Business Media, LLC 2009
Abstract A depside derivative, 2-(2-methoxy-2-oxoeth-
yl)phenyl 2-(3,4-dimethoxyphenyl)acetate (3), was synthe-
sized through a facile approach in high yields. Its structure
named jaboticabin, was demonstrated to inhibit chemokine
interleukin (IL)-8 production before and after exposure of
cells to cigarette smoke [10].
1
was confirmed by H NMR, 13C NMR, ESI mass spectra,
In order to discover novel antibacterial agents, our group
has designed two series of novel depside derivatives and
evaluated their antibacterial activities against three Gram
positive bacterial strains and three Gram negative bacterial
strains by the MTT method [11]. Biological results showed
that most compounds exhibited potent antibacterial activity
against the six bacterial strains. In this paper, we describe
the synthesis and crystal structure of compound 3.
elemental analyses and X-ray single crystal diffraction
study. Crystal structure analysis revealed that compound 3
crystallized in the monoclinic, space group P21/c with the
˚
following unit cell parameters: a = 10.173(2) A, b =
˚
˚
10.459(2) A, c = 16.516(3) A, a = 90°, b = 102.30(3)°,
3
˚
c = 90°, V = 1717.0(6) A , Z = 4.
Keywords Synthesis ꢀ Crystal structure ꢀ Depside
Experimental
Introduction
Proton NMR spectra were obtained at 300 and 500 MHz on
Bruker spectrometers in DMSO-d6. MS spectra were
recorded with a mariner system 5304 mass spectrometer.
Melting points were obtained by using a Boetius micro
melting point apparatus. Flash-column chromatographies
were performed on silica gel Merck Kieselgel 60 (230–400
mesh). Thin-layer chromatographies were performed on
silica gel plates (GF254, Merk); spots were detected visually
by ultraviolet irradiation (254 nm).The synthesis of com-
pound 3 followed the general pathway outlined in Scheme 1.
Depsides are compounds comprised of two or more aro-
matic rings bound by a phenolic oxygen-ester linkage.
Previous studies indicate that several depsides exhibit
antiproliferative, antibacterial, analgesic, antipyretic, anti-
cancer, anti HIV-1 integrase and antiviral properties [1–8].
Furthermore, as inhibitors of prostaglandin biosynthesis
and leukotriene B4 biosynthesis, depsides are potent non-
steroidal antiinflammatories [9]. Recently, a new depside,
Synthesis of Compound 2
P.-C. Lv ꢀ H.-L. Zhu
Key Laboratory of Anhui Educational Department,
Anhui University of Technology, 243002 Maanshan,
People’s Republic of China
A solution of 2-hydroxyphenylacetic acid (1) (7.6 g,
50 mmol) in methanol (50 mL) containing concd H2SO4
(5 mL) was refluxed overnight. After the methanol was
evaporated, water and ethyl acetate was added, the organic
phases were washed with saturated NaCl (100 mL) and
dried over Na2SO4, and the solvents were evaporated. This
step yields compound 2.
P.-C. Lv ꢀ K.-R. Wang ꢀ W.-J. Mao ꢀ R.-Q. Fang ꢀ J. Chen ꢀ
J. Xiong ꢀ H.-L. Zhu (&)
State Key Laboratory of Pharmaceutical Biotechnology,
Nanjing University, 210093 Nanjing,
People’s Republic of China
e-mail: zhuhl@nju.edu.cn
123

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J Chem Crystallogr (2009) 39:927–930
OH
OH
Crystal Structure Determination and Refinement
i
The crystal data, data collection and refinement parameters for
3 is listed in Table 1. Data were collected with a Bruker
SMART 1000 CCD diffractometer, using graphite mono-
OH
OCH3
˚
chromatized MoK a radiation (k = 0.71073 A) [12]. All cal-
O
O
2
1
culations were performed by using the SHELXTL-NT package
and refined with full matrix least-square procedures [13]. All
hydrogen atoms were located from a difference Fourier map
and were placed at calculated positions refined using a riding
model and hydrogen were given fixed isotropic thermal
parameters 1.2 times the atom to which they were attached.
CCDC 730485 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge by e-mailing data_request@ccdc.cam.ac.uk.
O
OCH3
ii
O
OCH3
OCH3
O
3
Scheme 1 (i) CH3OH; H2SO4; reflux. (ii) 3,4-Dimethoxyphenyl
acetic acid, DCC, DMAP, CH2Cl2, reflux
Results and Discussion
Figure 1 represents the crystal structure of compound 3
with thermal ellipsoids at 30% probability. It crystallizes in
Methyl 2-(2-Hydroxyphenyl)acetate (2)
White powder, yield 90%, mp: 61–62 °C, 1H NMR
(300 MHz, d6-DMSO): 3.54 (s, 2H); 3.58 (s, 3H); 6.78 (m,
2H); 7.06 (m, 2H); 9.47 (s, 1H). 13C NMR (DMSO-d6, d
ppm): 171.9, 155.5, 131.2, 128.2, 121.4, 118.9, 115.0, 51.6,
35.2. MS (ESI): 167.1 (C9H11O3, [M ? H]?). Anal. Calcd for
C9H10O3: C, 65.05; H, 6.07%; Found: C, 65.03; H, 6.10%.
Table 1 Crystallographic data for the title compound
Compound
CCDC number
Formula
3
730485
C
19H20O6
Mr
344.35
Crystal size (mm3)
Crystal system
Space group
0.30 9 0.20 9 0.20
Monoclinic
P21/c
Synthesis of Compound 3
˚
a (A)
10.173(2)
10.459(2)
16.516(3)
90
To a stirred solution of compound 2 (1.66 g, 10 mmol) in
dichloromethane (50 mL) was added 3,4-dimethoxyphenyl
acetic acid (2.35 g, 12 mmol), N,N-dimethylaminopyridine
(248 mg, 2.03 mmol) and N,N-dicyclohexylcarbodiimide
(2.26 g, 11 mmol). The mixture was refluxed overnight.
Flash chromatography (ethyl acetate: petroleum ether =
1:5) afforded the corresponding depside (compound 3) as a
white powder.
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
102.30(3)
90
3
˚
V (A )
1717.0(6)
4
Z
Dc(g/cm-3
)
1.332
l (mm-1
)
0.099
2-(2-Methoxy-2-oxoethyl)phenyl 2-(3,4-
Dimethoxyphenyl)acetate (3)
F(000)
728
Max. and min. trans.
h range (°)
Index range (h, k, l)
Reflections collected/unique
Data/restraints/parameters
Goodness-of-fit on F2
0.9804 and 0.9708
2.05–25.38
-12/11, 0/12, 0/19
3121/3121
3121/48/214
1.096
Yield 85%, mp: 65–66 °C, 1H NMR (300 MHz, d6-DMSO):
3.49 (s, 2H); 3.51 (s, 3H); 3.72 (s, 3H); 3.73 (s, 3H); 3.82 (s,
2H); 6.84 (m, 1H); 6.90 (m, 1H); 6.94 (m, 1H); 7.08 (m, 1H);
7.18 (m, 1H); 7.30 (m, 2H). 13C NMR (DMSO-d6, d ppm):
170.8, 169.5, 159.6, 149.2, 135.3, 131.6, 131.1, 129.6, 128.2,
127.0, 122.6, 121.8, 115.4, 112.7, 55.1, 51.5, 35.2.MS (ESI):
344.1 (C19H20O6, [M ? H]?). Anal. Calcd for C19H20O6: C,
66.27; H, 5.85; Found: C, 66.38; H, 5.93.
a
b
R1 , wR2 [I [ 2r(I)]
R1, wR2 (all data)
0.0852/0.2070
0.1446/0.2457
0.282/-0.271
3
˚
(Dq)max, (Dq)min (e/A )
The colorless single crystal of compound 3 was grown
from a mixture solution of ethyl acetate: petroleum ether
(1:5, v/v) by slow evaporation at room temperature.
P
P
a
R ¼ jjFo ꢁ Fcjj= jFoj;
h
h
i.
h
ii
1=2
ꢀ
ꢁ
ꢀ
ꢁ
P
P
2
2
b
wR ¼
w Fo2 ꢁ Fc2
w Fo2
123

J Chem Crystallogr (2009) 39:927–930
929
angles are all within normal values. The packing diagram
in Fig. 2 shows the stacking pattern of compound 3, viewed
along the b axis.
In the crystal structure of compound 3, there are two
benzene rings in the molecule. C(4), C(5), C(6), C(7), C(8)
and C(9) form the first plane with the mean deviation of
˚
0.0080 A, defined as plane I; Similarly, C(12), C(13),
C(14), C(15), C(16) and C(17) forms the second plane with
˚
the mean deviation of 0.0066 A, defined as plane II. The
dihedral angle between plane I and plane II is 108.9°. In
addition, the ester group (C(10), C(11), O(3) and O(4))
˚
form the third plane with the mean deviation of 0.0059 A,
defined as plane III. The dihedral angle between plane I
and plane III is 63.9°, while the dihedral angle between
plane II and plane III is 61.0°. Furthermore, the ester group
(O(1), C(2), C(3) and O(2)) form the fourth plane with the
Fig. 1 Molecular structure of the title compound with 30% proba-
bility of the ellipsoids
the monoclinic, space group P21/c with the following
˚
mean deviation of 0.0116 A, defined as plane IV. The
˚
unit cell parameters: a = 10.173(2) A, b = 10.459(2) A,
˚
dihedral angle between plane I and plane IV is 84.8°, while
the dihedral angle between plane II and plane IV is 73.1°,
and the dihedral angle between plane III and plane IV is
107.6°.
˚
c = 16.516(3) A, a = 90°, b = 102.30(3)°, c = 90°, V =
3
1717.0(6) A , Z = 4. The crystallographic data are pre-
˚
sented in Table 1, and selected bond lengths/angles and
torsion angles are given in Table 2. The bond lengths and
In addition, two intermolecular hydrogen bonds are as
˚
follows: C(5)-H(5A)ꢀꢀꢀO(4)#1 has length 3.316(6) A and an
angle of 146.9°, with symmetry code #1: -x, y - 1/2,
-z ? 1/2, and C(17)–H(17A)ꢀꢀꢀO(6)#2 has length
˚
Table 2 Selected bond lengths (A) and bond angles (°) of the title
compound
˚
3.480(5) A and an angle of 160.4°, with symmetry code #1:
-x ? 1, y - 1/2, -z ? 1/2 (Table 3).
Compound
3
˚
Bond lengths (A)
C(2)–O(1)
1.175(5)
C(2)–O(2)
1.310(5)
1.349(5)
1.203(5)
1.418(6)
1.358(5)
1.334(5)
1.390(5)
O(3)–C(10)
O(4)–C(10)
C(18)–O(5)
C(19)–O(6)
C(16)–O(5)
C(15)–O(6)
Bond angles (°)
C(1)–O(2)–C(2)
O(1)–C(2)–O(2)
O(1)–C(2)–C(3)
C(9)–O(3)–C(10)
O(3)–C(10)–O(4)
C(11)–C(10)–O(4)
C(16)–O(5)–C(18)
C(15)–O(6)–C(19)
Torsion angles (°)
C(1)–O(2)–C(2)–C(3)
C(2)–C(3)–C(4)–C(9)
C(10)–C(11)–C(12)–C(17)
C(10)–O(3)–C(9)–C(8)
C(19)–O(6)–C(15)–C(14)
C(18)–O(5)–C(16)–C(17)
116.1(4)
126.2(4)
125.9(4)
117.5(4)
123.0(4)
127.2(4)
115.2(4)
116.3(4)
175.5(5)
-87.5(5)
63.0(5)
64.2(5)
-20.3(6)
3.6(7)
Fig. 2 Packing of the molecules viewing along b axis. Dashed lines
represent hydrogen bonds
123

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J Chem Crystallogr (2009) 39:927–930
˚
4. Proksa B, Adamcova J, Sturdikova M, Fuska J (1994) Pharmazie
49:282
Table 3 Hydrogen bonds for the title compound (A and °)
D–HꢀꢀꢀA
D–H
HꢀꢀꢀA
DꢀꢀꢀA
D–HꢀꢀꢀA
5. Yamamoto Y, Miura Y, Kinoshita Y, Higuchi M, Yamada Y,
Murakami A, Ohigashi H, Koshimizu K (1995) Chem Pharm Bull
43:1388
6. Kumar KCS, Muller K (1999) J Nat Prod 62:821
7. Nielsen J, Nielsen PH, Frisvad JC (1998) Phytochemistry 50:263
8. Neamati N, Hong H-X, Mazumder A, Wang S-M, Sunder S,
Nicklaus MC, Milne WA, Proksa B, Pommier Y (1997) J Med
Chem 40:942
C(5)–H(5A)ꢀꢀꢀO(4)#1
C(17)–H(17A)ꢀꢀꢀO(6)#2
Symmetry transformations used to generate equivalent atoms: #1; -x,
y - 1/2, -z ? 1/2; #2; -x ? 1, y - 1/2, -z ? 1/2
0.93
0.93
2.50
2.59
3.318(6)
3.482(5)
146.5
160.4
9. Kumar KCS, Muller K (2000) Eur J Med Chem 35:405
10. Reynertson KA, Wallace AM, Adachi S, Gil RR, Yang H, Basile
MJ, Armiento JD, Weinstein B, Kennelly EJ (2006) J Nat Prod
69:1228
Acknowledgments The work was co-financed by grant (Project
30772627) from National Natural Science Foundation of China, and
by grant (Project 070416274X) from Anhui Natural Science Foun-
dation, Anhui Province, China.
11. Lv P-C, Xiao Z-P, Fang R-Q, Li H-Q, Zhu H-L, Liu C-H (2009)
Eur J Med Chem 44:1779
12. SMART 5.0 and SAINT 4.0 for Windows NT (1998) Area
detector control and integration software. Bruker Analytical X-
Ray Systems, Madison
13. Sheldrick GM (1997) SHELXTL: structure determination soft-
ware programs. Bruker Analytical X-Ray Systems, Madison
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