ArticlePDF Available

Five Unique Compounds: Xyloketals from Mangrove Fungus Xylaria sp. from the South China Sea Coast

Authors:

Abstract and Figures

Five unique metabolites, xyloketals A (1), B (2), C (3), D (4), and E (5), and the known 6 were isolated from mangrove fungus Xylaria sp. (no. 2508), obtained from the South China Sea. The structures of these compounds were elucidated by spectroscopic and X-ray diffraction experiments. Xyloketal A is a ketal compound with a C(3) symmetry and xyloketals B-E are its analogues. It was found that xytoketal C slowly rearranged to xytoketal B in DMSO-d(6)() solution at room temperature. Xyloketal A exhibited the activity of inhibiting acetylcholine esterase.
Content may be subject to copyright.
Five Unique Compounds: Xyloketals from Mangrove Fungus
Xylaria sp.from the South China Sea Coast
Yongcheng Lin,*,† Xiongyu Wu,Shuang Feng,Guangce Jiang,Jinghui Luo, Shining Zhou,
L. L. P. Vrijmoed,E. B. G. Jones,Karsten Krohn,§Klaus Steingro¨ver,§and Ferenc Zsila|
Department of Applied Chemistry, Zhongshan University, Guangzhou, P. R. China, Department of
Biology and Chemistry, City University of Hong Kong, Hong Kong, Fachbereich Chemie und
Chemietechnik, Universita¨t Paderborn, Warburger Strasse 100, D-33098 Paderborn, Germany, and
Department of Molecular Pharmacology, Institute of Chemistry CRC,
H-1525 Budapest, P.O.B. 17, Hungary
ceslyc@zsulink.zsu.edu.cn
Received January 13, 2001
Five unique metabolites, xyloketals A (1),B(2),C(3),D(4), and E (5), and the known 6were
isolated from mangrove fungus Xylaria sp. (no. 2508), obtained from the South China Sea. The
structures of these compounds were elucidated by spectroscopic and X-ray diffraction experiments.
Xyloketal A is a ketal compound with a C3symmetry and xyloketals B-E are its analogues. It was
found that xytoketal C slowly rearranged to xytoketal B in DMSO-d6solution at room temperature.
Xyloketal A exhibited the activity of inhibiting acetylcholine esterase.
Introduction
A large variety of new bioactive compounds have
recently been isolated from different sources of organ-
isms. A group that has yielded rich new bioactive
compounds are the marine fungi,1,2 especially the man-
grove fungi. It was reported that most described marine
fungi could be found from mangroves. Recently, we have
embarked on a study of the metabolites of marine fungi
including those from mangroves from the South China
Sea, and this has yielded a number of interesting
compounds.3,4
The mangrove fungus strain no. 2508, which was
collected from seeds of an angiosperm tree and identified
as Xylaria species (Ascomycota), was found to produce
rich secondary metabolites. Xyloketals A (1),B(2),C(3),
D(4), and E (5) were isolated from the fermentation broth
of this fungus. The xyloketals represent a series of novel
ketal compounds having a close biogenetic relationship.
In the primary bioassay, xyloketal A inhibited acetyl-
choline esterase at 1.5 ×10-6mol/L (p<0.01).
Results and Discussion
The ethyl acetate extract of a fermentation broth of
the fungus was repeatedly chromatographed on silica gel
using a gradient elution from petroleum to ethyl acetate.
Compound 1was obtained from the fraction eluted with
8% ethyl acetate/petroleum ether as colorless block
crystals, mp 164-166 °C. The NMR spectra of 1were
quite simple (Table 1).
There were merely nine signals (two CH3, two CH2,
two CH, and three C). The elemental composition was
determined as C9H12O2by the elemental analysis. How-
ever, the FABMS showed the molecular ion peak at 457
(M +1), which is three times the mass of C9H12O2. Thus,
the molecule was composed of the same three partial
structures in the same chemical environment. The COSY
spectrum revealed a contiguous sequence from H-4 to
H-7. The correlation between H-11 and H-5 located CH3-
11 at C-5. In the HMBC spectrum, the correlations
between C-2 and H-4, H-7, H-10 and the correlations
between C-8 and H-7, H-6 and between C-9 and H-7,
respectively, established the partial structure in fragment
A(Figure 1).
Three fragments A assembled to give the intact mol-
ecule 1. The structure of 1was finally confirmed by X-ray
diffraction analysis that showed the relative configura-
tions of 1to be 2R*,5R*,6R*. Compound 1is a chiral
Zhongshan University.
City University of Hong Kong.
§Universita¨t Paderborn.
|Institute of Chemistry CRC.
(1) Faulkner, D. J. Nat. Prod. Rep.1999 and previous reports in
this series.
(2) Fenical, W. Chem. Rev.1993,93, 1673-1683.
6252 J. Org. Chem. 2001, 66, 6252-6256
10.1021/jo015522r CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/25/2001
molecule with C3of symmetry, [R]D)-4.88°. The three
furan rings have cis configuration (Figure 2). Compound
2was isolated from the fraction eluted with 50% ethyl
acetate/petroleum ether. It was a colorless gelatinous
solid, mp 84-86 °C. Most of the NMR spectral data of 2
were similar to 1, but the signals appeared in pairs, and
there were a phenolic hydroxyl proton (δH6.14) and an
aromatic CH (δH6.13, δC95.9) in the NMR spectra of 2.
The FABMS of 2showed a molecular ion peak at m/z
347 (M +1) that was 110 mass less than that of 1. This
number is equal to losing an “arm” from 1and adding a
hydroxyl group. The structure of 2was determined by
comparing its spectra, mainly 2D NMR, with those of 1.
In the HMBC spectrum, most correlation signals were
similar to those of 1(Table 2). The correlations between
C-12 and H-7and between C-9 and H-13 could be used
to assigned the position of the OH group. The coupling
constants in the 1HNMR spectrum of 2are nearly
identical to those of 1, and the ROESY spectrum showed
the correlation between H-6 and H-11, implying the same
stereochemistry at C-2, C-5, and C-6.
The polarity of 3was greater than that of 2. Compound
3was obtained as colorless needles, mp >260 °C. The
molecular ion peak of 3at 347 (M +1) in the FABMS
and the elemental composition C20H26O5determined by
elemental analysis were identical to that of 2. Compound
3also carried a phenolic hydroxyl group (δH8.39) and
an aromatic CH (δH5.65, δC95.8). However, the NMR
Table 1. NMR Data of 1 (CDCl3TMS)
no. 13C1H1H-1H COSY HMBC ROESY
2 107.4 (C) H-4, 7, 10
4 74.0 (CH2) (a) 3.53 (a) H-4b, 5 H-5 (a) H-4b, 5
(b) 4.17 (b) H-4a, 5 (b) H-4a, 5
5 35.5 (CH) 2.14 (ddd, J)6.5, 8.5, 8.5 Hz) H-4, 6, 11 H-6, 11 H-4, 6, 11
6 47.6 (CH) 1.89 (dd, J)6.5, 11.0 Hz) H-5, 7 H-7, 11 H-5, 7, 10, 11
7 18.9 (CH2) (a) 2.64 (dd, J)6.5, 18.0 Hz) (a) H-6, 7b (a) H-6, 7b, 11,
(b) 2.85 (d, J)18.0 Hz) (b) H-6, 7a (b) H-6, 7a, 10
8 98.9 (C) H-6, 7
9 149.8 (C) H-7
10 22.9 (CH3) 1.50 (s) H-6, 7a
11 16.1 (CH3) 1.05 (d, J)6.5 Hz) H-5 H-5, 6, 7b
Table 2. NMR Data of 2 (CDCl3TMS)
no. 13C1H1H-1H COSYaHMBCaROESYa
2 107.4 (C) H-4, 6, 7, 10
2107.7 (C) H-4,6,7,10
4 74.0 (CH2) (a) 3.50 (dd, 8.5, 17.0 Hz) (a) H-4b, 5 H-5, 11
(b) 4.17 (dd, 7.5, 17.0 Hz) (b) H-4a, 5
474.0 (CH2) (a) 3.55 (dd, 8.5, 17.0 Hz) (a) H-4b, 5H-5,11
(b) 4.10 (dd, 6.5, 17.0 Hz) (b) H-4a, 5
5 35.5 (CH) 2.13 (m) H-4, 6,11 H-6, 7, 11 H-6
535.3 (CH) 2.14 (m) H-4,6,11H-6,7,11H-6
6 47.8 (CH) 1.88 (ddd, 1.0, 4.0, 6.5 Hz) H-5, 7 H-4, 10, 11 H-5, 11
647.5 (CH) 1.91 (ddd, 1.0, 4.5, 7.0 Hz) H-5,7H-4,10,11H-5,11
7 18.6 (CH2) (a) 2.62 (dd, 6.5, 17.0 Hz) H-6, 7b H-5, 6
(b) 2.80 (d, 17.0 Hz) H-6, 7a
718.4 (CH2) (a) 2.82 (d, 16.0 Hz) H-6,7b H-5,6
(b) 2.69 (dd, 7.0, 16.0 Hz) H-6,7a
8 99.4 (C) H-6, 7, 13
898.5 (C) H-6,7,13
9 152.0 (C) H-7, 13
9152.1 (C) H-7,13
10 22.8 (CH3) 1.50 (s) H-6
1023.1 (CH3) 1.52 (s) H-6
11 15.9 (CH2) 1.05 (d, 7.0 Hz) H-5 H-4, 6 H-6
1116.1 (CH2) 1.07 (d, 7.0 Hz) H-5H-4,6H-6
12 153.2 (C) H-7, 13, OH
13 95.9 (CH) 6.13 (s)
14 OH 6.14 (s)
aThe signals symbolized with and without a prime were not resolvable.
Figure 1. Correlation of HMBC of 2and a.
Figure 2. Molecular structure of 1.
Xyloketals from Mangrove Fungus Xylaria J. Org. Chem., Vol. 66, No. 19, 2001 6253
spectra of 3are more similar to those of 1than 2and
did not inhibit pairs of peaks. This suggested symmetry
in the molecule. The COSY, ROESY, and HMBC spectra
proved the structure of 3(see Table 3). The correlations
between the OH and C-12, C-8, respectively, located the
OH at C-12. According to the optical rotation of 3(R)
52.4°) and an X-ray experiment,the stereochemistry of
the chiral centers could be assigned.
The polarity of 4was the lowest of the five compounds.
It was isolated as colorless blocks, mp 111-113 °C. In
the NMR spectrum of 4(Table 4), there are similar
signals as found in 1, additional signals due to an acetyl
group, a hydroxyl group, and two vicinal aromatic CH
groups. Compound 4had the molecular formula C15H18O4
as determined by FABMS and elemental analysis. These
data suggested that 4was also an analogue of 1losing
two “arms”. The downfield signal of the OH at δ13.09
indicated that it was located on the ortho position to the
acetyl group. In the HMBC spectrum of 4, the correla-
tions between C-8 and both H-6 and the OH defined the
position of two substitutents on the benzene ring.
Compound 5was eluted following 1,mp170-172 °C.
Its structure was elucidated by comparing the spectra
with those of the other xyloketals. The structures of 3-5
were further confirmed by X-ray single-crystal structure
analysis. (Figure 3 and Supporting Information).
The absolute configuration of xyloketals A (1) and D
(4) at the stereogenic centers 2, 5, and 6 can either be
all-Sor all-R, since their relative configurations are
known from X-ray analysis. Both polycyclic compounds
have rather rigid structures and thus a limited number
of stable conformations. Therefore, they are suitable
substrates for quantum mechanical calculations of their
CD spectra as employed previously by us in the palmaru-
mycin6or preussomerin series.7Comparison with experi-
mental data then leads to matching and mismatching
curves, allowing the assignment of the absolute config-
uration.
(3) Lin, Y. C.; Shao, Z. Y.; Jiang, G.; Zhou, S.; Cai, J.; Vrijmoed, L.
L. P.; Jones, E. B. G. Tetrahedron 2000,56, 9607-9609.
(4) Lin, Y. C.; Wu, X. Y.; Fen, S.; Jiang, G.; Zhou, S.; Vrijmoed, L.
L. P. Jones, E. B. G. Tetrahedron Lett. 2001,42, 449-451.
(5) (a) Windholz, M. Merck Index, 10th ed.; Merck & Co., Inc.:
Rahway, NJ, 1984; p 1174. (b) Sadtler Standary Carbon-13 NMRS,
Vols. 61-64, 12316.
(6) Bringmann, G.; Busemann, S.; Krohn, K.; Beckmann, K. Tetra-
hedron 1997,53, 1655-1664.
(7) Krohn, K.; Flo¨rke, U.; John, M.; Root, N.; Steingro¨ver, K.; Aust,
H.-J.; Draeger, S.; Schulz, B.; Antus, S.; Simonyi, M.; Zsila, F.
Tetrahedron 2001,57, 4343-4348.
Table 3. NMR Data of 3 (CDCl3TMS)
no. 13C1H1H-1H COSY HMBC ROESY
2 106.6 (C) H-4, 5, 7
4 72.8 (CH2) (a) 3.36 (t, 8.0 Hz) (a) H-4b, 5 H-11 (a) H-4b, 5
(b) 3.96 (t, 8.0 Hz) (b) H-4a, 5 (b) H-4a, 5
5 34.8 (CH) 1.89 (overlap) H-4, 11 H-4, 6, 7, 11 H-4, 11
6 47.1 (C) 1.86 (overlap) H-7 H4, 5, 7, 11,10 H-7, 11
7 18.6 (CH2) (a) 2.65 (dd, 6.0, 17.0 Hz) (a) H-6, 7b (a) H-6, 7b
(b) 2.76 (d, 17.0 Hz) (b) H-6, 7a (b) H-6, 7a
8 99.2 (C) H-6, 7, 13, OH
9 151.9 (C) H-7, 13
10 22.8 (CH3) 1.37 (s)
11 15.4 (CH3) 0.99 (d, 6.0 Hz) H-5 H-4, 5 H-5, 6
12 153.0 (C) OH
13 95.8 (CH) 5.65 (s)
OH 8.39 (s)
Table 4. NMR Data of 4 (CDCl3TMS)
no. 13C1H COSY HMBC ROESY
2 108.3 (C) H-4, 7, 10
4 74.3 (CH2) (a) 3.57 (t, 8.0 Hz) (a) H-4b, 5 H-11 (a) H-4b
(b) 4.20 (t, 8.0 Hz) (b) H-4a, 5 (b) H-4a
5 35.1 (CH) 2.15 (m) H-4, 6, 11 H-4, 6, 7, 11 H-4
6 47.0 (CH) 1.98 (ddd, 1.0, 6.5, 11.0 Hz) H-5, 7 H-4, 7, 10, 11 H-7b, 11
7 18.0 (CH2) (a) 2.72 (dd, 6.5, 18.0 Hz) (a) H-6, 7b (a) H-7b
(b) 2.97 (d, 18.0 Hz) (b) H-6, 7a (b) H-6, 7a
8 106.2 (C) H-6, 7, 15, OH
9 159.5 (C) H-7, 14
10 22.7 (CH3) 1.53 (s)
11 15.8 (CH3) 1.07 (d, 7.0 Hz) H-5 H-6, 7b
12 162.9 (C) H-7, 14, OH
13 113.2 (C) H-15, 17, OH
14 130.0 (CH) 7.51 (d, 9.0 Hz) H-15 H-15
15 108.8 (CH) 6.36 (d, 9.0 Hz) H-14 H-14
16 202.6 (C) H-14, 17
17 26.1 (CH3) 2.54 (s)
18 OH 13.09 (s)
Figure 3. Molecular structure of 5.
6254 J. Org. Chem., Vol. 66, No. 19, 2001 Lin et al.
The conformational analysis of the more simple xylo-
ketal D (4), using the Spartan force field package,8shows
that the five-membered ring is relatively rigid and only
the six-membered ring shows some flexibility. The cal-
culations showed the existence of only two major con-
formers from which the CD spectra were calculated
employing the BDZDO/MCDPPD program package of
Downing as modified by Fleischhauer.9The Boltzmann-
weighted calculated CD spectrum was then compared
with the experimental spectrum (dotted line). As shown
in Figure 4, the experimental spectrum matches that of
the calculated spectrum for the 2R,5R,6Rconfiguration
of xyloketal D (4).
Not surprisingly, the calculation of the xyloketal A (1)
conformation showed a similar rigidity of the five-
membered ring and some conformational flexibility of the
six-membered rings. Since three six-membered rings are
involved in 1, the CD spectra of more conformations had
to be calculated in this case. The agreement of the
Boltzmann-weighted spectra with the experimental spec-
trum was not as perfect as for xyloketal D (4) (Figure 5).
The strong negative Cotton effect resulting from the 1Ba,b
transition of the UV spectrum at 210 nm was shifted by
13 nm to lower wavelength. However, the similar shape
of the curves and the same strong negative Cotton effect
leaves no doubt that the absolute configuration of xy-
loketal A (1) is also 2R,5R,6Rat the relevant stereogenic
centers in the three heterocyclic parts of the C3-sym-
metric molecule.
The known compound 6was also isolated in relatively
large amounts from the fungus. This may be useful for
the deduction of the biogenesis of the xyloketals.
The analysis of the spectra of these xyloketals revealed
some regularities; for example, in the FABMS of the
compounds, they all showed strong M -(98)1-2peaks,
which could be caused by the loss of one or two 1,4-
dimethyl-4,5-dihydrofuran fragments via a retro hetero-
Diels-Alder reaction. It was found that 3slowly trans-
formed to 2in DMSO-d6over 3 months, which indicated
that a rearrangement was occurring. Further studies are
in progress.
Experimental Section
General Methods. NMR data were recorded on a Varian
Inova 500NB NMR spectrometer, mass spectra on a VG-ZAB-
HS mass spectrometer, IR spectra on a Bruker EQUINOX 55
spectrophotometer, UV spectra on a Shimadzu UV-2501PC
spectrophotometer, optical rotations on a Horiba high-sensitiv-
ity polarimeter SEPA-300, elemental analyses on a Elementar
Vario EL CHNS-O elemental analyzer, and X-ray data on a
Bruker Smart 1000 CCD system diffractometer.
Fungal Strain. A strain of the fungus Xylaria sp. (no. 2508)
was isolated from seeds of an angiosperm tree in Mai Po, Hong
Kong, and was stored at the Department of Applied Chemistry,
Zhongshan University, Guangzhou, China.
Culture Conditions. Starter cultures (from Professor E.
B. G. Jones and Dr. L. L. P. Vrijmoed) were maintained on
cornmeal seawater agar. Plugs of agar supporting mycelial
growth were cut and transferred aseptically to a 250 mL
Erlenmeyer flask containing 100 mL of liquid medium (glucose
10 g/L, peptone 2 g/L, yeast extract 1 g/L, NaCl 30 g/L). The
flask was incubated at 30 °C on a rotary shaker for 5-7 days.
The mycelium was aseptically transferred to a 300-L fermenter
containing 170 L of GYT medium, incubated at 30 °C for 80
h. Extraction and Separation of Metabolites. The cultures
(170 L) were filtered through cheesecloth. The filtrate was
concentrated to 3.5 L below 50 °C and extracted five times by
shaking with an equal volume of ethyl acetate. The combined
extracts were chromatographed on silica gel using a gradient
elution from petroleum to ethyl acetate, to obtain 4(30 mg),
1(1.9 g), and 5(50 mg) in turn from the 8% ethyl acetate/
petroleum ether fraction. The known compound 6(3.2 g) and
then 2(2.3 g) and 3(23 mg) were eluted in turn from the 50%
fraction.
Compound 1: colorless blocks; mp 164-166 °C; [R]25D)
-4.88° (c0.205, CHCl3); IR (KBr) cm-12955, 2930, 2905, 2844,
1622, 1459, 1383, 1327, 1299, 1180, 1112, 1099, 1046, 1018,
931, 868, 699; UV λmax (CHCl3) 222 (14 370), 224 (14 300),
228 (14 000), 272 (1274); 1H NMR, 13C NMR, and 2D NMR,
see Table 1; FABMS m/z45 (M +1), 456, 441, 397, 359, 315,
299, 259, 245, 217, 175, 163, 111, 83,55. Anal. Calcd for
C27H36O6: C, 71.05; H, 7.95. Found: C 71.13, H 7.74.
Compound 2: colorless gelatinous solid; mp 84-86 °C;[R]25D
)+8.2° (c0.061, CHCl3); IR (KBr) cm-13356, 2962, 2935,
2891, 1622, 1508, 1454, 1342, 1190, 1117, 1069, 876, 818, 612;
UV λmax (CHCl3) 215 (68 790), 228 (41620), 274 (9827);
1H NMR, 13C NMR, and 2D NMR, see Table 2; FABMS m/z
347 (M +1), 346, 289, 249, 205, 189, 151, 111, 97, 83, 55. Anal.
Calcd for C20H26O5: C, 69.36; H, 7.52. Found: C, 69.39; H,
7.35.
Compound 3: colorless needles; mp >260 °C; [R]25D)-52.4°
(c0.038, CHCl3); IR (KBr) cm-13357, 3056, 2982, 2953, 2905,
1627, 1595, 1491, 1450, 1381, 1337, 1223, 1191, 1113,1077,
987, 877, 810, 598, 569; UV λmax (CHCl3) 215 (15 060), 227 (
9758), 275 (1515); 1H NMR, 13C NMR, and 2D NMR, see
(8) Spartan SGI Version 5.1.3, Wavefunction Inc., Irvine.
(9) Downing, J. W. Program package BDZDO/MCDSPD, Depart-
ment of Chemistry and Biochemistry, University of Colorado, Boulder,
CO; modified by J. Fleischhauer, W. Schleker, B. Kramer; ported to
LinuX by K.-P. Gulden.
Figure 4. Experimental CD spectrum and calculated spec-
trum (dotted line) of xyloketal A (1).
Figure 5. Experimental CD spectrum and calculated spec-
trum (dotted line) of xyloketal D (4).
Xyloketals from Mangrove Fungus Xylaria J. Org. Chem., Vol. 66, No. 19, 2001 6255
Table 3; FABMS m/z347 (M +1), 346, 329, 289, 249, 205,
189, 176,149, 111, 89, 77, 57. Anal. Calcd for C20H26O5:C,
69.36; H, 7.52. Found: C, 68.81; H, 7.82.
Compound 4: colorless blocks; mp 111-113 °C; [R]25D)
-119.5° (c0.113, CHCl3); IR (KBr) cm-13479, 3416, 3089,
3056, 2954, 2921, 2879, 1615, 1492, 1420, 1381, 1332, 1261,
1117, 1070, 1002, 854, 831, 804, 641, 609; UV λmax (CHCl3)
220 (17 450), 228 (10 720), 280 (18 040), 307 (8766); 1H
NMR, 13C NMR, and 2D NMR, see Table 4; FABMS m/z263
(M +1), 247, 203, 177, 165, 147, 111, 97, 83, 55. Anal. Calcd
for C15H18O4: C, 68.70; H, 6.87. Found: C, 68.80; H, 7.20.
Compound 5: colorless blocks; mp 170-172 °C; [R]25D)
+5.35° (c0.374, CHCl3); 1H NMR (CDCl3)δ1.00 (d, J)6.5
Hz, 3H), 1.04 (d, J)6.5 Hz, 3H), 1.08 (d, J)6.5 Hz, 3H),
1.48 (s), 1.50 (s, 3H), 1.53 (s, 3H), 1.78 (m, H), 1.84 (m, H),
1.90 (dd, J)7, 12 Hz, H), 2.06 (m, H), 2.17 (m, H), 2.38 (m,
H), 2.58 (dd, J)17.0, 7.0 Hz, H), 2.64 (dd, J)17.0, 7.0 Hz,
H), 2.81 (d, J)17.0 Hz, H), 2.83 (d, J)17.0 Hz, H), 2.86 (dd,
J)6.0, 12.0 Hz, H), 3.38 (dd, J)8.0, 10.5 Hz, H), 3.46 (J)
8.5 Hz, H), 3.54 (J)8.5 Hz, H), 4.06 (dd, J)7.0, 10.5 Hz,
H), 4.08 (t, J)8.5 Hz, H), 4.16 (t, J)8.5 Hz, H), 10.81 (s,
OH), 13CNMR (CDCl3)δ15.5 (CH3), 16.3 (CH3), 16.2(CH3), 19.1
(CH2), 18.7 (CH2), 22.5 (CH3), 23.0 (CH3), 28.4 (CH3), 32.7 (CH),
35.4 (CH), 35.7 (CH), 47.0 (CH), 47.7 (CH), 49.3 (CH2), 73.9
(CH2), 74.0 (CH2), 74.2 (CH2), 89.1 (C), 98.2 (C), 98.8 (C), 107.3
(C), 107.5 (C), 110.8 (C), 148.3 (C), 150.2 (C), 152.0(C); FABMS
445 (M +1), 444, 429, 385, 347, 331, 287, 249; UV λmax (CHCl3)
216 (17 510), 226 (11 390), 273 (1450). Anal. Calcd for
C20H26O5: C, 70.27; H, 8.11. Found: C, 70.53; H, 8.42.
Compound 6: colorless needles; mp 143-144.5 °C; 1H NMR
(CDCl3)δ2.58 (s, 3H), 5.72 (s, OH), 6.40 (s, 1H), 6.41 (d, J)
8.5 Hz, 1H), 7.65 (d, J)8.5 Hz, 1H) 12.69 (s, OH); 13C NMR
(CDCl3)δ26.2, 103.5, 107.7, 114.4, 133.1, 162.6, 165.1, 202.7.5
X-ray crystallographic data of 1: crystal system, space
group monoclinic, P21; unit cell dimensions a)10.0760(15)
Å, R)90°; b)13.2084(19) Å, β)116.725(2)°; c)10.1571(15)
Å, γ)90°; volume )1207.4(3) Å3,Z)2, Dcalcd )1.256 Mg/
m3,m)0.087 mm-1,F000 )4492. All single-crystal data were
collected using the hemisphere technique on a Bruker SMART
1000 CCD system diffractometer with graphite-monochro-
mated Mo KRradiation λ)0.7l0 73 at 293(2) K. The
structures were solved by direct methods using SHELXTLV5.0
(Siemens IndustriaI Automation lnc, Madison, WI) and refined
using full-matrix least-squares difference Fourier techniques.
All non-hydrogen atoms were refined with anisotropic dis-
placement parameters, and all hydrogen atoms were placed
in idealized positions and refined as riding atoms with the
relative isotropic parameters. Absorption corrections were
applied with the Siemens area detector absorption program
(SADABS). The final value of Rwas 0.0332, wR2 )0.0903 [I
>2σ(I)].
X-ray Crystallography of 4. The conditions and methods
of the experiment were the same as those used for compound
1: crystal system, space group monoclinic, P21; unit cell
dimensions a)5.3820 (10) Å, R)90°; b)8.5550(10) Å, β)
93.64(2)°; c)14.952(2) Å, γ)90°; volume )687.0(2) Å3,Z)
2, Dcalcd )1.268 Mg/m3,m)0.091 mm-1,F000 )280. The
final value of Rwas 0.0675, wR2 )0.1310 [I>2σ(I)].
X-ray Crystallography of 5. The conditions and methods
of the experiment were the same as those used for compound
1: crystal system, space group monoclinic, P21; unit cell
dimensions a)7.8868(12) Å, R)90°; b)10.2975(15) Å, β)
92.328(3)°; c)15.237(2) Å, γ)90°; volume )1236.4(3) Å3,Z
)2, Dcalcd )1.194 Mg /m3, absorption coefficient m)0.084
mm-1,F(000) )480, crystal size 0.35 ×0.13 ×0.11 mm; final
Rindices [I>2σ(I)], R1 )0.0465, wR2 )0.118.
Acknowledgment. We thank Prof. D. J. Faulkner
and C. H. Heathcock for reading the manuscript. This
work was supported by the National Natural Science
Foundation of China (29672053 and 20072058), the
Natural Science Foundation of Guangdong Province,
China (950026 and 980317), the Star Lake Biotechnol-
ogy Co., Inc., Zhaoqing Guangdong, China, and a
strategic grant at City University of Hong Kong
(7000650). E.B.G.J. acknowledges the Royal Society,
U.K.. and City University of Hong Kong for the award
of the Kan Tong Po Visiting Professorship.
Supporting Information Available: 1HNMR of 3and
X-ray crystal structure data of 1,3,4, and 5. This material is
available free of charge via the Internet at http://pubs.acs.org.
JO015522R
6256 J. Org. Chem., Vol. 66, No. 19, 2001 Lin et al.
... The symmetry of molecular building blocks plays a pivotal role in the overall geometry of the materials that are formed. Besides many examples of C 2 -symmetric [1] building blocks, the C 3 -symmetrical ones have found fewer applications, other than in life sciences [2] or material sciences. However, C 3 -symmetrical-based geometries can be found in star-shaped molecules, dendrimers, and molecular cages [3], thus allowing the formation of columnar structuring due to strong π-π interactions in the case of appropriately functionalized monomers [4] (for reviews, see Ref. [5]). ...
Article
Full-text available
A series of C3-symmetric fully substituted benzenes were prepared based on alkyl triamino-benzene-tricarboxylates. Starting with a one step-synthesis, the alkyl triamino-benzene-tricarboxylates were synthesized using the corresponding cyanoacetates. The reactivity of these electronically sophisticated compounds was investigated by the formation of azides, the click reaction of the azides and a Sandmeyer-like reaction. Caused by the low stability of triaminobenzenes, direct N-alkylation was rarely reported. The use of the stable alkyl triamino-benzene-tricarboxylates allowed us total N-alkylation under standard alkylation conditions. The molecular structures of the C3-symmetric structures have been corroborated by an X-ray analysis.
... Many studies lack information on the media used [94,95]. Lin et al. [96] and Toske et al. [97] specify that 30 g/L of NaCl and 100% seawater, respectively, were used for the fermentation medium. Janso et al. [98] explored the effect of media with 5, 10, 15 or 20% NaCl on the growth of Penicillium dravuni with the metabolites dityosphaeric acids A and B and carviolin produced in fermentation with 50% artificial seawater. ...
Article
Abstract: With the over 2000 marine fungi and fungal-like organisms documented so far, some have adapted fully to life in the sea, while some have the ability to tolerate environmental conditions in the marine milieu. These organisms have evolved various mechanisms for growth in the marine environment, especially against salinity gradients. This review highlights the response of marine fungi, fungal-like organisms and terrestrial fungi (for comparison) towards salinity variations in terms of their growth, spore germination, sporulation, physiology, and genetic adaptability. Marine, freshwater and terrestrial fungi and fungal-like organisms vary greatly in their response to salinity. Generally, terrestrial and freshwater fungi grow, germinate and sporulate better at lower salinities, while marine fungi do so over a wide range of salinities. Zoosporic fungal-like organisms are more sensitive to salinity than true fungi, especially Ascomycota and Basidiomycota. Labyrinthulomycota distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). and marine Oomycota are more salinity tolerant than saprolegniaceous organisms in terms of growth andreproduction. Wide adaptability to saline conditions in marine or marine-related habitats requires mechanisms for maintaining accumulation of ions in the vacuoles, the exclusion of high levels of sodium chloride, the maintenance of turgor in the mycelium, optimal growth at alkaline pH, a broad temperature growth range from polar to tropical waters, and growth at depths and often under anoxic conditions, and these properties may allow marine fungi to positively respond to the challenges that climate change will bring. Other related topics will also be discussed in this article, such as the effect of salinity on secondary metabolite production by marine fungi, their evolution in the sea, and marine endophytes. Keywords: ocean acidification; adaptation; deep sea; global warming; mangrove fungi; physiology; stress response; transcriptome; seawater
... Many studies lack information on the media used [94,95]. Lin et al. [96] and Toske et al. [97] specify that 30 g/L of NaCl and 100% seawater, respectively, were used for the fermentation medium. Janso et al. [98] explored the effect of media with 5, 10, 15 or 20% NaCl on the growth of Penicillium dravuni with the metabolites dityosphaeric acids A and B and carviolin produced in fermentation with 50% artificial seawater. ...
Article
Full-text available
With the over 2000 marine fungi and fungal-like organisms documented so far, some have adapted fully to life in the sea, while some have the ability to tolerate environmental conditions in the marine milieu. These organisms have evolved various mechanisms for growth in the marine environment, especially against salinity gradients. This review highlights the response of marine fungi, fungal-like organisms and terrestrial fungi (for comparison) towards salinity variations in terms of their growth, spore germination, sporulation, physiology, and genetic adaptability. Marine, freshwater and terrestrial fungi and fungal-like organisms vary greatly in their response to salinity. Generally, terrestrial and freshwater fungi grow, germinate and sporulate better at lower salinities, while marine fungi do so over a wide range of salinities. Zoosporic fungal-like organisms are more sensitive to salinity than true fungi, especially Ascomycota and Basidiomycota. Labyrinthulomycota and marine Oomycota are more salinity tolerant than saprolegniaceous organisms in terms of growth and reproduction. Wide adaptability to saline conditions in marine or marine-related habitats requires mechanisms for maintaining accumulation of ions in the vacuoles, the exclusion of high levels of sodium chloride, the maintenance of turgor in the mycelium, optimal growth at alkaline pH, a broad temperature growth range from polar to tropical waters, and growth at depths and often under anoxic conditions, and these properties may allow marine fungi to positively respond to the challenges that climate change will bring. Other related topics will also be discussed in this article, such as the effect of salinity on secondary metabolite production by marine fungi, their evolution in the sea, and marine endophytes.
... Among the endophytic fungi most frequently found among species of Baccharis, the genera Xylaria and Preussia deserve to be highlighted with regard to their metabolism. Species of Xylaria are known to produce several chemical constituents of the terpene class (Smith et al. 2002), xanthones (Healy et al. 2004), cyclopeptides (Huang et al. 2007), and xyloketals (Lin et al. 2001), among others. Species of this genus are found in other plant species of the family Asteraceae and are known for their inhibitory activity against phytopathogens such as Penicillium expansum (Bleicher and Bernardi 1985;Costa and Veiga 1996) and Aspergillus niger (Lock 1962;Santos et al. 2010). ...
Chapter
Endophytic fungi are important mediators in the structure and dynamics of terrestrial plant communities and their relationships with associated fauna. Although endophytic fungi are found in all living plants, only 1% of all Baccharis species (Baccharis artemisioides, B. coridifolia, B. dracunculifolia, B. megapotamica, and B. trimera) have had their endophytic mycota studied. To date, 28 genera of endophytic fungi have been identified in association with species of Baccharis. Analysis of the enzymes and metabolites produced by this mycota indicates that these endophytes have numerous properties that may be related to better performance and resistance of their Baccharis host to several stressors and natural enemies. Many of these endophytes have properties that can be exploited for the development of beneficial applications in the fields of agronomy, pharmacology, and conservation, making them a particularly important group for the development of biotechnological products.
Article
A Brønsted acid catalyzed tandem process to access densely functionalized chromeno[3,2-d]isoxazoles with good to excellent yields and diastereoselectivities was disclosed. The procedure is proposed to involve a 1,6-conjugate addition/electrophilic addition/double annulations process of alkynyl o-quinone methides (o-AQMs) in situ generated from o-hydroxyl propargylic alcohols with nitrones. Mild conditions, good functional group compatibility, easy scale-up of the reaction, and further product transformation demonstrated its potential application.
Chapter
Fungi are one of the important components of almost all ecosystems on the earth, including aquatic habitats ranging from high montane lakes down to the deep oceans. However, the fungal aquatic environments have remained largely unexplored. Fungi play an essential role in the cycling of nutrients and food web dynamics. Thus, the distinctive properties of aquatic fungi make them a good source for biochemical and industrial applications. Fungi are a major source of pharmaceuticals used in many industrial processes (fermentation), such as the production of enzymes, vitamins, pigments, glycolipids, polysaccharides, lipids, and other bioactive molecules. Aquatic fungi, especially hyphomycetes, are becoming increasingly important because of their ability to resist anthropogenic stress. In aquatic fungi, both extracellular and intracellular mechanisms that involve a complex network of pathways are used for metal tolerance and detoxification. Fungi can metabolize organic xenobiotics indicating that these species play a role in attenuating aquatic pollutants and may have potential use in environmental biotechnology.
Article
Covering: June 2009 to 2021Natural products containing a phloroglucinol motif include simple and oligomeric phloroglucinols, polycyclic polyprenylated acylphloroglucinols, phloroglucinol-terpenes, xanthones, flavonoids, and coumarins. These compounds represent a major class of secondary metabolites which exhibit a wide range of biological activities such as antimicrobial, anti-inflammatory, antioxidant and hypoglycaemic properties. A number of these compounds have been authorized for therapeutic use or are currently being studied in clinical trials. Their structural diversity and utility in both traditional and conventional medicine have made them popular synthetic targets over the years. In this review, we compile and summarise the recent synthetic approaches to the natural products bearing a phloroglucinol motif. Focus has been given on ingenious strategies to functionalize the phloroglucinol moiety at multiple positions. The isolation and bioactivities of the compounds are also provided.
Article
Nonalcoholic fatty liver disease (NAFLD) represents a class of disorders including hepatic steatosis, steatohepatitis, and liver fibrosis. Previous research suggested that xyloketal B (Xyl-B), a marine-derived natural product, could attenuate the NAFLD-related lipid accumulation. Herein, we investigated the protective mechanism of Xyl-B in a high-fat diet (HFD) mice fatty liver model by combining a quantitative proteomic approach with experimental methods. The results showed that the administration of Xyl-B (20 and 40 mg·kg-1·day-1, ip) ameliorated the hepatic steatosis in HFD mice. Proteomic profiling together with bioinformatics analysis highlighted the upregulation of a cluster of peroxisome proliferator-activated receptor-α (PPARα) downstream enzymes mainly related to fatty acid oxidation (FAO) as key changes after the treatment. These changes were subsequently confirmed by bioassays. Moreover, further results showed that the expression levels of PPARα and PPARγ coactivator-1α (PGC1α) were increased after the treatment. The related mode-of-action was confirmed by PPARα inhibition. Furthermore, we evaluated the PPARα-mediated anti-inflammatory and antifibrosis effect of Xyl-B in methionine-choline-deficient (MCD) mice hepatitis and liver fibrosis models. According to the results, the histological features were improved, and the levels of inflammatory factors, adhesion molecules, as well as fibrosis markers were decreased after the treatment. Collectively, these results indicated that Xyl-B ameliorated different phases of NAFLD through activation of the PPARα/PGC1α signaling pathway. Our findings revealed the possible metabolism-regulating mechanism of Xyl-B, broadened the application of xyloketal family compounds, and may provide a new strategy to curb the development of NAFLD.
Article
Herein, we report a straightforward one-pot synthesis of tetrahydrofurobenzopyran and tetrahydrofurobenzofuran systems via an in situ ring-expansion of the cyclopropane carbaldehydes followed by a [2 + n] cycloaddition with the quinone derivatives. The transformation not only unveils a new reaction mode of cyclopropane carbaldehydes with quinone methides/esters, but also promotes a step-efficient diastereoselective route to the sophisticatedly fused oxygen tricycles that can be further dehydrogenated to access the valued dihydro-2H-furo[2,3-b]chromene frameworks.
Chapter
Abstract Xylaria is the largest genus of the family Xylariaceae (Xylariales, Sordariomycetes) and presently consists of ca. 300 accepted species of stromatic pyrenomycetes. They are popularly known as dead man’s finger, have common distribution in soil, leaf litter, woody litter, and termite mounds. In addition, they also have mutualistic association as endophytes in tropical and temperate plant species. The xylarial stromata constitutes one of the important raw biomaterials in traditional Chinese and other ethnic medicinal systems. The genus Xylaria is a major source of a wide range of bioactive compounds (sesquiterpenoids, terpenoids, cytochalasins, mellein, alkaloids, polyketides, and aromatic compounds). Some of the metabolites of Xylaria deploy antibacterial, antifungal, anticancer, antimalarial, anti-inflammatory, and α-glucosidase inhibitory activities. The metabolites of Xylaria are also known for potential herbicidal, fungicidal, and insecticidal activities. Xylaria is known for the production of many volatile and non-volatile compounds and their volatiles are functional in various pharmaceutical and agricultural applications. This review covers the bioactive metabolites reported from different species of Xylaria and along with their source of origin and biological properties.
Article
Full-text available
Three known preussomerins, G (1), H (2) and I (3), and three new representatives, J (4), K (5) and L (6), were isolated from an endophytic fungus, a Mycelia sterila, from Atropa belladonna. Their absolute configuration was determined by comparison of calculated and experimental CD spectra.
Article
The quantumchemical calculation of the CD spectra of two representatives of palmarumycins biologically active compounds from Coniothyrium species, is described, allowing, for the first time, the elucidation of the absolute configuration of two representatives of this class of compounds without the use of empirical rules or reference material.
Article
A novel cyclic peptide containing an allenic ether of a N-(p-hydroxycinnamoyl)amide, and two aromatic allenic ethers were isolated from the endothytic fungus Xylaria sp. from the South China Sea. Their structures were determined by analysis of spectroscopic data, mainly 2D NMR experiments.
Article
Penicillazine (1) is a new compound with both quinolone and 4H-5,6-dihydro-1,2-oxazine ring systems that was isolated from a culture of the marine fungus Penicillium sp. (strain #386). Its structure was elucidated using spectroscopic methods, primarily 2D NMR techniques, and was confirmed by an X-ray diffraction analysis. Variations in the 1H NMR spectrum of penicillazine (1) were observed over a 65°C temperature range.
48 (s), 1.50 (s, 3H), 1.53 (s, 3H), 1.78 (m, H), 1.84 (m, H), 1.90 (dd, J ) 7, 12 Hz
  • Hz
Hz, 3H), 1.04 (d, J ) 6.5 Hz, 3H), 1.08 (d, J ) 6.5 Hz, 3H), 1.48 (s), 1.50 (s, 3H), 1.53 (s, 3H), 1.78 (m, H), 1.84 (m, H), 1.90 (dd, J ) 7, 12 Hz, H), 2.06 (m, H), 2.17 (m, H), 2.38 (m, H), 2.58 (dd, J ) 17.0, 7.0 Hz, H), 2.64 (dd, J ) 17.0, 7.0 Hz, H), 2.81 (d, J ) 17.0 Hz, H), 2.83 (d, J ) 17.0 Hz, H), 2.86 (dd, J ) 6.0, 12.0 Hz, H), 3.38 (dd, J ) 8.0, 10.5 Hz, H), 3.46 (J )
81 (s, OH), 13 CNMR (CDCl3) δ 15
  • H Hz
Hz, H), 3.54 (J ) 8.5 Hz, H), 4.06 (dd, J ) 7.0, 10.5 Hz, H), 4.08 (t, J ) 8.5 Hz, H), 4.16 (t, J ) 8.5 Hz, H), 10.81 (s, OH), 13 CNMR (CDCl3) δ 15.5 (CH3), 16.3 (CH3), 16.2(CH3), 19.1 (CH2), 18.7 (CH2), 22.5 (CH3), 23.0 (CH3), 28.4 (CH3), 32.7 (CH), 35.4 (CH), 35.7 (CH), 47.0 (CH), 47.7 (CH), 49.3 (CH2), 73.9 (CH2), 74.0 (CH2), 74.2 (CH2), 89.1 (C), 98.2 (C), 98.8 (C), 107.3
81 (s, OH), 13 CNMR (CDCl3) δ 15.5 (CH3)
  • Hz
Hz, H), 3.54 (J ) 8.5 Hz, H), 4.06 (dd, J ) 7.0, 10.5 Hz, H), 4.08 (t, J ) 8.5 Hz, H), 4.16 (t, J ) 8.5 Hz, H), 10.81 (s, OH), 13 CNMR (CDCl3) δ 15.5 (CH3), 16.3 (CH3), 16.2(CH3), 19.1 (CH2), 18.7 (CH2), 22.5 (CH3), 23.0 (CH3), 28.4 (CH3), 32.7 (CH), 35.4 (CH), 35.7 (CH), 47.0 (CH), 47.7 (CH), 49.3 (CH2), 73.9 (CH2), 74.0 (CH2), 74.2 (CH2), 89.1 (C), 98.2 (C), 98.8 (C), 107.3 (C), 107.5 (C), 110.8 (C), 148.3 (C), 150.2 (C), 152.0(C); FABMS 445 (M + 1), 444, 429, 385, 347, 331, 287, 249; UV λmax (CHCl3) 216 ( 17 510), 226 ( 11 390), 273 ( 1450). Anal. Calcd for C20H26O5: C, 70.27;
5 X-ray crystallographic data of 1: crystal system, space group monoclinic
  • C Nmr
Hz, 1H), 7.65 (d, J ) 8.5 Hz, 1H) 12.69 (s, OH); 13 C NMR (CDCl3) δ 26.2, 103.5, 107.7, 114.4, 133.1, 162.6, 165.1, 202.7. 5 X-ray crystallographic data of 1: crystal system, space group monoclinic, P21; unit cell dimensions a ) 10.0760(15)
and previous reports in this series
  • D Faulkner