Naturally occurring 1,2,8-trimethoxyxanthone and biphenyl ether intermediates leading to 1,2-dimethoxyxanthone.

Article abstract of DOI:10.1107/S010827010101349X

In order to study structure-activity relationships, a series of mono-, di- and trioxygenated xanthones has been synthesized and the structures of methyl 2-(3,4-dimethoxyphenoxy)benzoate, C(16)H(16)O(5), 2-(3,4-dimethoxyphenoxy)benzoic acid, C(15)H(14)O(5), 1,2-dimethoxy-9H-xanthen-9-one, C(15)H(12)O(4), and 1,2,8-trimethoxy-9H-xanthen-9-one, C(16)H(14)O(5), have been determined. The first two compounds both assume skew conformations, the dihedral angles between the two phenyl rings being 80.04 (8) and 83.0 (1) degrees, respectively. The latter two compounds are essentially planar and their methoxy substituents assume orientations consistent with minimum steric interactions.

Full text of DOI:10.1107/S010827010101349X

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
xanthones 1,2,8-trimethoxy-9H-xanthen-9-one, (IV), and
1,3,5,7-tetramethoxyxanthone (Kijjoa et al., 2000). However,
the biological activities of these xanthones have not yet been
evaluated. Taking into account the variety of biological
properties of xanthones, we have planned the synthesis of a
series of 1,2-dioxygenated xanthones to evaluate their anti-
tumour and immunomodulatory activities. The syntheses of
some 1,2-dioxygenated xanthones have been reported
previously; 1,2-dimethoxy-9H-xanthen-9-one, (III), was
obtained in very low yield by a multi-step synthesis of its
intermediate 1-formyl-2-hydroxyxanthone (Golberg & Wragg,
1958). More recently, 1-hydroxy-2-methoxyxanthone has been
prepared by an LDA-induced (LDA is lithium diisopropyl-
amide) regiospeci®c route from diaryl ether 2-carbohexamines
(Familoni et al., 1997). In contrast, we have succeeded in
preparing (III) by a facile one-step conversion of the diaryl
intermediate 2-(3,4-dimethoxyphenoxy)benzoic acid, (II), into
the corresponding xanthone. In this paper, we report the
structures of the intermediate compounds, methyl 2-(3,4-di-
methoxyphenoxy)benzoate, (I), and 2-(3,4-dimethoxy-
phenoxy)benzoic acid, (II), obtained during the synthesis of
(III), as well as the structure of this xanthone compared with
(IV), which is very similar and which was isolated from a plant.
ISSN 0108-2701
Naturally occurring 1,2,8-trimethoxy-
xanthone and biphenyl ether inter-
mediates leading to 1,2-dimethoxy-
xanthone
Luis Gales,a,b Maria Emilia de Sousa,c,d Madalena M. M.
Pinto,c Anake Kijjoaa,c and Ana M. Damasa,b
*
a
Ã
Â
Instituto de Ciencias Biomedicas Abel Salazar, Universidade do Porto, Largo Prof.
Abel Salazar N. 2, 4099-003 Porto, Portugal, bInstituto de Biologia Molecular e
Celular, Universidade do Porto, R. Campo Alegre N. 823, 4150 Porto, Portugal,
c
Â
Ã
Â
Centro de Estudos de Quõmica Organica, Fitoquõmica e Farmacologia, Faculdade de
Â
Farmacia, Universidade do Porto, Rua Anibal Cunha, 4050-017 Porto, Portugal, and
d
Ã
Â
Instituto Superior de Ciencias de Saude do Norte, Gandra, Portugal
Correspondence e-mail: amdamas@ncc.up.pt
Received 18 May 2001
Accepted 13 August 2001
In order to study structure±activity relationships, a series of
mono-, di- and trioxygenated xanthones has been synthe-
sized and the structures of methyl 2-(3,4-dimethoxyphenoxy)-
benzoate, C16H16O5, 2-(3,4-dimethoxyphenoxy)benzoic acid,
C15H14O5, 1,2-dimethoxy-9H-xanthen-9-one, C15H12O4, and
1,2,8-trimethoxy-9H-xanthen-9-one, C16H14O5, have been
determined. The ®rst two compounds both assume skew
conformations, the dihedral angles between the two phenyl
rings being 80.04 (8) and 83.0 (1)ꢀ, respectively. The latter two
compounds are essentially planar and their methoxy substi-
tuents assume orientations consistent with minimum steric
interactions.
Comment
Xanthones are major secondary metabolites of the plants of
the family Guttiferae (Bennett & Lee, 1989). Both synthetic
and naturally occurring xanthones have been reported to
mediate various biological effects, such as hepatoprotection
(Fernandes et al., 1995) and reversible monoamine oxidase A
inhibitors (Thull et al., 1993; Fujimoto et al., 1998). As part of
our ongoing research concerning the variety of biological
properties of this class of compounds, we have investigated the
xanthone constituents of Calophyllum teysmanii var.
inophylloide and studied their immunomodulatory activity
(Gonzalez et al., 1999).
Among the xanthones tested, 2-hydroxy-1-methoxy-
xanthone has been shown to exhibit the highest inhibitory
activity on T-cell proliferation. Further examination of the
extract of Calophyllum teysmanii var. inophylloide has led to
an isolation of, among many known xanthones, the new
Compounds (I) and (II) (Figs. 1 and 2) differ only in the
substituent at C2, which is a methyl ester in (I) and a
carboxylic acid group in (II). They both assume a skew
conformation, the angle between the phenyl rings being
80.04 (8)ꢀ for (I) and 83.0 (1)ꢀ for (II). These angles are in
close agreement with the value of 84.8 (1)ꢀ observed in
another open-ring intermediate for the synthesis of xanthones
(Damas et al., 1997).
In (I), the plane de®ned by C1, O1 and C10 makes an angle
of 4.8 (1)ꢀ with the C1±C6 phenyl ring plane and 76.5 (2)ꢀ with
the other ring, C10±C60. The methyl ester group is nearly
coplanar with the phenyl ring, as shown by the r.m.s. devia-
tions from the ring plane: C7 0.039 (3), O2 0.173 (4), O3
Ê
0.079 (4) and C10 0.029 (6) A. Furthermore, the bond
ꢁ
Acta Cryst. (2001). C57, 1319±1323
# 2001 International Union of Crystallography
Printed in Great Britain ± all rights reserved 1319

organic compounds
C40ÐC30ÐO4ÐC8 179.8 (2)ꢀ], as in (I). Compound (II) also
shows two intermolecular hydrogen bonds: O3Á Á ÁO2i
i
Ê
Ê
2.612 (3) A and O3Á Á ÁO3 3.449 (4) A [symmetry code: (i)
1
given in Table 3.
x, y, 3 z]. Further details of these hydrogen bonds are
The 1,2-dimethoxy-9H-xanthen-9-one molecule in (III) is
nearly planar (Fig. 3); the three rings de®ne a plane, with an
Ê
r.m.s. deviation for the ®tted atoms of 0.030 A. The maximum
deviation of the O atoms, which were not included in the
Ê
calculation of the least-squares plane, is 0.14 A for O13. Of the
two methoxy substituents on the phenyl ring, one methyl
group lies much further out of the ring plane than does the
other [C2ÐC1ÐO11ÐC11 102.5 (3)ꢀ, compared with C1Ð
C2ÐO12ÐC12 179.1 (3)ꢀ]. Atom C11 is probably forced out
of the phenyl plane due to the proximity of atoms O13 and
O12. Adoption of these orientations by phenyl rings with
multiple methoxy substituents has been observed previously
and is consistent with minimum steric interactions (Hibbs et
al., 1995; Kijjoa et al., 1998).
Figure 1
The molecular structure of (I) showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii.
angles between the methyl ester group and the phenyl-ring C
atoms adjacent to C2 are 126.3 (2)ꢀ for C1ÐC2ÐC7 and
115.8 (2)ꢀ for C3ÐC2ÐC7. The difference between these
angles (10.5ꢀ) is probably due to a requirement of minimum
steric interaction between the methyl ester group and the
other phenyl ring.
In the 1,2,8-trimethoxy-9H-xanthen-9-one compound, (IV),
isolated from the wood of Callophyllum teysmanii var.
inophylloide, two of the methyl groups of the three methoxy
The two methoxy substituents do not diverge signi®cantly
from the ring plane, as shown by the torsion angles C30ÐC40Ð
O5ÐC9 [177.8 (2)ꢀ] and C40ÐC30ÐO4ÐC8 [176.9 (2)ꢀ].
Again, the orientation of the two methoxy substituents
appears to have been determined by the requirement of
minimum steric interaction between them.
In (II), the C1±C6 phenyl ring is nearly coplanar with the
C1/O1/C10 plane, the relevant angle being 1.4 (2)ꢀ. The angle
between the other ring, C10±C60, and the C1/O1/C10 plane is
84.3 (2)ꢀ. The carboxylic acid group is nearly coplanar with the
phenyl ring, the r.m.s. deviations from the ring plane being
Ê
0.036 (3), 0.132 (4) and 0.034 (4) A for C7, O2 and O3,
Figure 3
respectively. The C1ÐC2ÐC7 angle of 124.1 (2)ꢀ is 6.2ꢀ wider
than the C3ÐC2ÐC7 angle [117.9 (2)ꢀ]; this difference is
smaller than observed for (I), probably because the substi-
tuent in (I) is larger. The two methoxy substituents are in the
plane of the phenyl ring [C30ÐC40ÐO5ÐC9 179.2 (2)ꢀ and
The molecular structure of (III) showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii.
Figure 4
Figure 2
The molecular structure of (IV) showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii. Atom C12 wholly
obscures one of the attached H atoms.
The molecular structure of (II) showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii.
ꢁ
1320 Luis Gales et al.
C16H16O5, C15H14O5, C15H12O4 and C16H14O5
Acta Cryst. (2001). C57, 1319±1323

organic compounds
Compound (I)
substituents are much closer to the plane of the molecule than
the third (Fig. 4), as shown by the torsion angles C1ÐC2Ð
O12ÐC12 [ 162.0 (2)ꢀ], C2ÐC1ÐO11ÐC11 [79.6 (3)ꢀ] and
C7ÐC8ÐO13ÐC13 [3.9 (4)ꢀ]. As in (III), atom C11 lies out
of the ring plane, probably to minimize the steric interactions
due to the presence of atoms O12 and O14 on either side of
the methoxy group.
Papers describing the biological activities of these four
compounds are in preparation. Comparison of the three-
dimensional structure of molecules (III) and (IV) with those
of the xanthone constituents of Calophyllum teysmanii var.
inophylloide, whose activities have been studied, will reveal
details of the relationship between structure and activity for
this class of compounds.
Crystal data
3
C16H16O5
Mr = 288.29
Monoclinic, P21/c
Dx = 1.322 Mg m
Mo Kꢁ radiation
Cell parameters from 1232
re¯ections
Ê
a = 15.306 (7) A
b = 7.788 (4) A
ꢂ = 5.0±28.1ꢀ
ꢃ = 0.10 mm
T = 293 (2) K
Ê
1
Ê
c = 16.426 (7) A
ꢀ = 132.31 (3)ꢀ
V = 1448.0 (12) A
Z = 4
3
Ê
Square prism, colourless
0.30 Â 0.25 Â 0.20 mm
Data collection
Stoe IPDS diffractometer
Image-plate ' scans
13 194 measured re¯ections
3439 independent re¯ections
2221 re¯ections with I > 2ꢄ(I)
Rint = 0.068
ꢂmax = 28.1ꢀ
h = 20 ! 19
k = 10 ! 10
l = 21 ! 21
Intensity decay: none
Re®nement
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.055
wR(F2) = 0.165
S = 1.05
3439 re¯ections
w = 1/[ꢄ2(Fo2) + (0.068P)2
+ 0.376P]
Experimental
where P = (Fo2 + 2Fc2)/3
(Á/ꢄ)max < 0.001
The synthesis of (I) [step (1) in the Scheme] was carried out according
to the method of Fernandes et al. (1995). A mixture of methyl
2-bromobenzoate (16.2 g, 75 mmol), 3,4-dimethoxyphenol (11.9 g,
77 mmol), copper bronze (9.8 g, 155 mmol) and Na2CO3 (21.3 g,
154 mmol) in dry pyridine (240 ml) was thoroughly degassed with
nitrogen and re¯uxed for 26 h. The mixture was then cooled to room
temperature, ®ltered and concentrated, furnishing a dark-brown oily
liquid which was dissolved in methylene chloride and then washed
with 0.5 M NaOH. The organic layer was dried over Na2SO4, ®ltered
and concentrated under reduced pressure to provide an oily brown
liquid (18.2 g). This was puri®ed by column chromatography [petro-
leum ether (313±333 K boiling fraction)/diethyl ether (5:5)].
Evaporation of the solvent under reduced pressure furnished a solid
product, (I) (9.0 g, 41%), which was crystallized from a diethyl ether/
n-hexane mixture.
3
Ê
Áꢅmax = 0.23 e A
3
Ê
0.22 e A
254 parameters
All H-atom parameters re®ned
Áꢅmin
=
Table 1
Selected bond lengths (A) for (I).
Ê
O1ÐC1
O1ÐC10
O4ÐC30
O4ÐC8
O5ÐC40
O5ÐC9
O2ÐC7
O3ÐC7
O3ÐC10
C10ÐC60
C10ÐC20
1.370 (3)
1.405 (2)
1.371 (2)
1.429 (3)
1.369 (2)
1.422 (3)
1.200 (2)
1.310 (3)
1.444 (3)
1.368 (3)
1.393 (3)
C20ÐC30
C30ÐC40
C40ÐC50
C50ÐC60
C1ÐC6
C1ÐC2
C2ÐC3
C2ÐC7
C3ÐC4
C4ÐC5
C5ÐC6
1.389 (3)
1.410 (3)
1.383 (3)
1.397 (3)
1.391 (3)
1.411 (3)
1.394 (3)
1.493 (3)
1.380 (3)
1.387 (3)
1.377 (3)
The synthesis of (II) [step (2) in the Scheme] was carried out
according to the method of Fernandes et al. (1995). Compound (I)
(8.2 g, 28 mmol) was dissolved in methanol/tetrahydrofuran (1:1) and
treated with aqueous 5 M NaOH solution (12 ml) at room tempera-
ture for 96 h. The crude product was washed with ether, and the
aqueous layer was separated, washed with methylene chloride,
acidi®ed with 5 M HCl and extracted with methylene chloride. The
organic phase was dried over Na2SO4, ®ltered and concentrated
under reduced pressure, furnishing a white solid, (II) (7.6 g, 98%),
which was crystallized from methylene chloride.
Compound (II)
Crystal data
The synthesis of (III) [step (3) in the Scheme] was carried out
according to the method of Fernandes et al. (1995). To a 2 M solution
of LDA in tetrahydrofuran/heptane/ethylbenzene (2.5 ml, 5 mmol), a
solution of (II) (2.688 mg, 2.5 mmol) in dry tetrahydrofuran (25 ml)
was added dropwise over 1 h at 273 K under a nitrogen atmosphere.
The reaction mixture was allowed to reach room temperature over
1 h. The reaction was quenched by addition of 5% HCl and then
extracted with methylene chloride. The organic phase was washed
with 5% Na2CO3, dried over Na2SO4, ®ltered and concentrated under
reduced pressure to furnish an oily brown liquid. This crude product
was puri®ed by column chromatography [chloroform/n-hexane (7:3)].
After evaporation of the solvent, the solid, (III) (476.3 mg, 74%), was
crystallized from a methylene chloride/n-hexane mixture.
C15H14O5
Z = 2
3
Mr = 274.26
Triclinic, P1
a = 7.920 (4) A
Dx = 1.356 Mg m
Mo Kꢁ radiation
Cell parameters from 854
re¯ections
Ê
Ê
b = 8.550 (5) A
ꢂ = 4.7±24.2ꢀ
ꢃ = 0.10 mm
T = 293 (2) K
Ê
c = 11.360 (7) A
1
ꢁ = 76.02 (7)ꢀ
ꢀ = 82.46 (7)ꢀ
ꢆ = 64.20 (6)ꢀ
Rectangular prism, colourless
0.7 Â 0.4 Â 0.3 mm
3
Ê
V = 671.8 (7) A
Data collection
Stoe IPDS diffractometer
Image-plate ' scans
4584 measured re¯ections
1923 independent re¯ections
1618 re¯ections with I > 2ꢄ(I)
Rint = 0.047
ꢂmax = 24.1ꢀ
h = 9 ! 8
k = 9 ! 9
Compound (IV) was isolated from the wood of Callophyllum
teysmanii var. inophylloide according to the method of Kijjoa et al.
(2000).
l = 12 ! 12
Intensity decay: none
ꢁ
Acta Cryst. (2001). C57, 1319±1323
Luis Gales et al.
C16H16O5, C15H14O5, C15H12O4 and C16H14O5 1321

organic compounds
Re®nement
Table 4
Selected bond lengths (A) for (III).
Ê
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.050
wR(F2) = 0.159
S = 1.06
1923 re¯ections
189 parameters
H atoms treated by a mixture of
independent and constrained
re®nement
w = 1/[ꢄ2(Fo2) + (0.098P)2
+ 0.065P]
where P = (Fo2 + 2Fc2)/3
(Á/ꢄ)max = 0.001
O10ÐC10a
O10ÐC4a
O11ÐC1
O11ÐC11
O12ÐC2
O12ÐC12
O13ÐC9
C2ÐC1
1.379 (3)
1.381 (3)
1.388 (3)
1.439 (4)
1.373 (3)
1.426 (4)
1.242 (3)
1.396 (4)
1.400 (4)
1.406 (4)
1.408 (4)
C9aÐC9
C8aÐC10a
C8aÐC8
C8aÐC9
C4aÐC4
C10aÐC5
C5ÐC6
C8ÐC7
C7ÐC6
C3ÐC4
1.480 (4)
1.397 (4)
1.412 (4)
1.465 (4)
1.389 (4)
1.387 (4)
1.372 (5)
1.365 (5)
1.400 (5)
1.376 (4)
3
Ê
Áꢅmax = 0.14 e A
3
Ê
0.15 e A
Áꢅmin
=
C2ÐC3
C9aÐC1
C9aÐC4a
Table 2
Selected bond lengths (A) for (II).
Ê
O1ÐC1
O1ÐC10
O2ÐC7
O3ÐC7
O4ÐC30
O4ÐC8
O5ÐC40
O5ÐC9
C40ÐC50
C40ÐC30
C1ÐC6
1.376 (2)
1.403 (2)
1.257 (3)
1.268 (2)
1.370 (2)
1.425 (3)
1.366 (2)
1.410 (3)
1.376 (3)
1.407 (3)
1.391 (3)
C1ÐC2
1.403 (3)
1.397 (3)
1.480 (3)
1.384 (3)
1.375 (3)
1.393 (3)
1.369 (3)
1.382 (3)
1.394 (3)
1.369 (3)
Compound (IV)
C2ÐC3
C2ÐC7
C30ÐC20
C6ÐC5
C20ÐC10
C10ÐC60
C5ÐC4
C50ÐC60
C3ÐC4
Crystal data
C16H14O5
Mr = 286.27
Orthorhombic, P212121
Mo Kꢁ radiation
Cell parameters from 1345
re¯ections
ꢂ = 4.1±24.2ꢀ
Ê
a = 5.2730 (10) A
1
Ê
b = 15.443 (4) A
ꢃ = 0.11 mm
T = 293 (2) K
Ê
c = 16.550 (6) A
Ê
V = 1347.7 (7) A
3
Rectangular prism, colourless
0.8 Â 0.5 Â 0.3 mm
Z = 4
Dx = 1.411 Mg m
3
Table 3
Hydrogen-bonding geometry (A, ) for (II).
Data collection
ꢀ
Ê
Stoe IPDS diffractometer
Image-plate ' scans
8453 measured re¯ections
2068 independent re¯ections
1887 re¯ections with I > 2ꢄ(I)
Rint = 0.039
ꢂmax = 24.2ꢀ
h = 5 ! 5
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
k = 17 ! 17
l = 18 ! 18
Intensity decay: none
O3ÐH3Á Á ÁO2i
0.82
0.82
1.81
2.78
2.612 (3)
3.449 (4)
168
140
O3ÐH3Á Á ÁO3i
Symmetry code: (i) 1 x; y; 1 z.
Re®nement
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.042
wR(F2) = 0.108
S = 1.03
2068 re¯ections
210 parameters
w = 1/[ꢄ2(Fo2) + (0.046P)2
+ 0.426P]
where P = (Fo2 + 2Fc2)/3
(Á/ꢄ)max = 0.001
Compound (III)
3
Ê
Áꢅmax = 0.14 e A
3
Ê
0.11 e A
Crystal data
Áꢅmin
=
H atoms treated by a mixture of
independent and constrained
re®nement
3
C15H12O4
Mr = 256.25
Monoclinic, P21/n
Dx = 1.407 Mg m
Mo Kꢁ radiation
Cell parameters from 1542
re¯ections
Ê
a = 4.953 (2) A
b = 13.930 (6) A
ꢂ = 3.7±24.1ꢀ
ꢃ = 0.10 mm
T = 293 (2) K
Ê
1
Ê
c = 17.670 (8) A
Table 5
Selected bond lengths (A) for (IV).
Ê
ꢀ = 97.23 (6)ꢀ
V = 1209.5 (9) A
Z = 4
3
Ê
Rectangular prism, yellow
0.60 Â 0.25 Â 0.20 mm
O10ÐC4a
O10ÐC10a
O11ÐC1
O11ÐC11
O12ÐC2
O12ÐC12
O13ÐC8
O13ÐC13
O14ÐC9
C8aÐC10a
C8aÐC8
1.375 (3)
1.379 (3)
1.372 (3)
1.438 (3)
1.378 (3)
1.413 (4)
1.360 (3)
1.436 (3)
1.229 (3)
1.403 (3)
1.424 (4)
1.470 (3)
C5ÐC6
C5ÐC10a
C8ÐC7
C4aÐC4
C4aÐC9a
C7ÐC6
C9aÐC1
C9aÐC9
C4ÐC3
C1ÐC2
C2ÐC3
1.371 (4)
1.382 (4)
1.385 (4)
1.388 (4)
1.396 (3)
1.395 (4)
1.404 (3)
1.488 (3)
1.379 (4)
1.398 (4)
1.387 (4)
Data collection
Stoe IPDS diffractometer
Image-plate ' scans
7542 measured re¯ections
1807 independent re¯ections
1225 re¯ections with I > 2ꢄ(I)
Rint = 0.056
ꢂ
max = 24.1ꢀ
h = 5 ! 5
k = 15 ! 15
l = 20 ! 20
Intensity decay: none
Re®nement
C8aÐC9
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.052
wR(F2) = 0.168
S = 1.07
1807 re¯ections
180 parameters
w = 1/[ꢄ2(Fo2) + (0.08P)2
+ 0.422P]
where P = (Fo2 + 2Fc2)/3
(Á/ꢄ)max = 0.001
All the H atoms in (I), H5 and H6 in (II), H4 and H8 in (III) and
the aromatic H atoms in (IV) were located from difference Fourier
maps and re®ned freely with isotropic displacement parameters. The
remaining H atoms could not be clearly located from the difference
maps, and were placed geometrically and re®ned riding on their
3
Ê
Áꢅmax = 0.17 e A
3
Ê
0.16 e A
Áꢅmin
=
H atoms treated by a mixture of
independent and constrained
re®nement
ꢁ
1322 Luis Gales et al.
C16H16O5, C15H14O5, C15H12O4 and C16H14O5
Acta Cryst. (2001). C57, 1319±1323

organic compounds
Ê
parent C atoms at distances of 0.93 (aromatic) and 0.96 A (methyl),
References
with Uiso(H) = xUeq(C), where x = 1.2 and 1.5 for aromatic and methyl
H atoms, respectively. A degree of racemic twinning was indicated for
compound (IV) and a twin correction with two equal components was
applied. This improved the re®nement marginally.
Bennett, G. J. & Lee, H.-H. (1989). Phytochemistry, 28, 967±998.
Damas, A. M., Roleira, F. F. & Pinto, M. M. (1997). Acta Cryst. C53, 1143±1145.
Familoni, O. B., Ionica, I., Bower, J. F. & Snieckus, V. (1997). Synlett, pp. 1081±
1083.
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.
For all four compounds, data collection: IPDS (Stoe & Cie, 1994);
cell re®nement: IPDS; data reduction: IPDS; program(s) used to
solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to
re®ne structure: SHELXL97 (Sheldrick, 1997); molecular graphics:
ORTEP-3 (Farrugia, 1997); software used to prepare material for
publication: SHELXL97 and ORTEP-3.
Fernandes, E. R., Carvalho, F. D., RemiaÄo, F. G., Bastos, M. L., Pinto, M. M. &
Gottlieb, O. R. (1995). Pharm. Res. 12, 1756±1760.
Flack, H. D. (1983). Acta Cryst. A39, 876±881.
Fujimoto, H., Satoh, Y., Yamaguchi, K. & Yamazaki, M. (1998). Chem. Pharm.
Bull. 46, 1506±1510.
Golberg, A. A. & Wragg, A. H. (1958). J. Chem. Soc. 80, 4227±4234.
Gonzalez, M. J., Nascimento, M. S. J., Cidade, H. M., Pinto, M. M. M., Kijjoa,
A., Anantachoke, C., Silva, A. M. S. & Herz, W. (1999). Planta Med. 65, 368±
371.
Hibbs, D. E., Hursthouse, M. B. & Malik, K. M. (1995). Acta Cryst. C51, 1891±
1893.
Kijjoa, A., Gonzalez, M. J., Afonso, C. M., Pinto, M. M., Anantachoke, C. &
Herz, W. (2000). Phytochemistry, 53, 1021±1024.
Kijjoa, A., Gonzalez, M. J., Pinto, M. M., Damas, A. M., Mondranondra, I.-O.,
Silva, A. M. & Herz, W. (1998). Phytochemistry, 49, 2159±2162.
Sheldrick, G. M. (1990). Acta Cryst. A46, 467±473.
Ã
We thank the FundacËaÄo para a Ciencia e Tecnologia
(Unidade de I&D No. 226/97), POCI (QCA III), PRAXIS
XXI (project No. Praxis/P/SAU/13236/1998) and FEDER for
support, and PRAXIS XXI for a scholarship for MES.
È
Sheldrick, G. M. (1997). SHELXL97. University of Gottingen, Germany.
Stoe & Cie (1994). IPDS User Manual. Version 2.4. Stoe & Cie, Darmstadt,
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: BM1457). Services for accessing these data are
described at the back of the journal.
Germany.
Thull, U., Kneubuhler, S., Testa, B., Borges, M. F. & Pinto, M. M. (1993).
È
Pharm. Res. 10, 1187±1190.
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Acta Cryst. (2001). C57, 1319±1323
Luis Gales et al.
C16H16O5, C15H14O5, C15H12O4 and C16H14O5 1323