Phenolic glycosides from the filamentous fungus Acremonium sp. BCC 14080

Article abstract of DOI:10.1021/np070689m

New phenolic mono- and digalactopyranosides (1 and 2), their aglycone KS-501a (3), and a new phenolic 4-O-methylglucopyranoside (4) were isolated from the filamentous fungus Acremonium sp. BCC 14080. Structures of these compounds were elucidated by extensive MS and NMR spectroscopic analyses. Compound 1 displayed anti-HSV-1 activity with an IC₅₀ value of 7.2 μM. Compound 3 exhibited activity against Plasmodium falciparum K1 with an IC ₅₀ value of 9.9 μM.

Full text of DOI:10.1021/np070689m

J. Nat. Prod. 2008, 71, 891–894
891
Phenolic Glycosides from the Filamentous Fungus Acremonium sp. BCC 14080
Taridaporn Bunyapaiboonsri,* Seangaroon Yoiprommarat, Artit Khonsanit, and Somjit Komwijit
National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand Science Park, 113 Paholyothin Road, Klong 1,
Klong Luang, Pathumthani 12120, Thailand
ReceiVed December 4, 2007
New phenolic mono- and digalactopyranosides (1 and 2), their aglycone KS-501a (3), and a new phenolic
4-O-methylglucopyranoside (4) were isolated from the filamentous fungus Acremonium sp. BCC 14080. Structures of
these compounds were elucidated by extensive MS and NMR spectroscopic analyses. Compound 1 displayed anti-
HSV-1 activity with an IC50 value of 7.2 µM. Compound 3 exhibited activity against Plasmodium falciparum K1 with
an IC50 value of 9.9 µM.
Fungi in the genus Acremonium have been isolated from plants,1,2
soil,3,4 and marine organisms.5,6 They are known to produce various
novel secondary metabolites, some that have biological activities
such as antitumor pentadecapeptides (efrapeptins),6 antibiotic and
antitumor pentacyclic polyketides (UCS1025A and B),7 an anti-
bacterial spirobenzofuran,8 and plant growth inhibitors (acremo-
lactones).9 As part of our research program on bioactive constituents
from Thai microorganisms,10 we describe herein the isolation of
two new depsides, 1 and 2, containing one and two galactopyranose
moieties, respectively, together with their aglycone, KS-501a (3),11
and a new phenolic 4-O-methylglucopyranoside (4) from Acremo-
nium sp. BCC 14080. Biological assays including antiplasmodial,
cytotoxic, and anti-HSV-1 activities of the isolated compounds are
also reported in this paper.
The culture broth extract of BCC 14080 was subjected to
Sephadex LH-20 and silica gel column chromatography to afford
compound 4 and a subfraction that was subsequently purified by
reversed-phase HPLC column chromatography to furnish compound
1. The crude mycelial extract was separated on a Sephadex LH-20
column to yield compounds 2 and 3.
Compound 1 was isolated as a white solid. The molecular
formula C33H48O10 was deduced from HRMS (ESITOF). The IR
spectrum showed absorption bands at 3423 (OH) and 1728 (ester
1
carbonyl) cm-1. H NMR, 13C NMR, and 2D NMR data (COSY,
NOESY, HMQC, and HMBC) revealed that 1 possessed a sugar
unit attached to a 3-heptyl-5-hydroxyphenyl 2-heptyl-4,6-dihy-
droxybenzoate (KS-501a).11 Analysis of 13C NMR and DEPT
spectra indicated the presence of an ester carbonyl (δC 166.4), four
oxygenated aromatic carbons (δC 159.8, 158.2, 157.2, 152.1), three
aromatic quaternary carbons (δC 145.2, 143.3, 115.5), five aromatic
methines (δC 112.8, 112.7, 110.4, 106.8, 101.5), 12 methylenes,
and two methyl groups for the aglycone unit. The 1H and 13C NMR
data of the aglycone were close to those of KS-501a reported in
the literature.11 For the sugar unit, an anomeric carbon (δC 103.0),
four oxymethine carbons (δC 75.7, 73.8, 71.4, 69.0), and an
oxymethylene carbon (δC 61.5) were observed from 13C NMR and
DEPT spectra. The vicinal coupling constants, J1′′,2′′ ) 7.7 Hz, J2′′,3′′
) 9.4 Hz, and J3′′,4′′ ) 3.3 Hz, suggested that H-1′′, H-2′′, and
H-3′′ were axial in orientation, while H-4′′ was equatorial in the
pyranose ring. NOESY cross signals observed from H-1′′ to H-3′′
and from H-1′′ to H-5′′ indicated that the sugar unit of 1 was
ꢀ-galactopyranose. Attachment of the sugar unit to C-2 of the
aglycone was established on the basis of HMBC correlation from
H-1′′ (δH 4.86) to C-2 (δC 157.2). The 1H NMR spectrum (in D2O)
D-galactose. The 1H NMR and MS data of the organic layer of the
hydrolysate were identical to 5-heptylresorcinol.12 Two molar
equivalents of 5-heptylresorcinol were obtained instead of an
equimolar mixture of 5-heptylresorcinol and 2-heptyl-4,6-dihy-
droxybenzoic acid, since thermal decarboxylation of 2-heptyl-4,6-
dihydroxybenzoic acid occurred to yield 5-heptylresorcinol.11,13
This result also confirmed that both alkyl chains attached to C-6
and C-5′ were the same (n-heptyl group).
The molecular formula of 2 was established as C39H58O15 on
the basis of HRESIMS. The 1H and 13C NMR data of the aglycone
of 2 were nearly identical to those of 1. For the sugar part, two
anomeric carbons (δC 103.9, 102.1), eight oxymethine carbons, and
two oxymethylene carbons (δC 68.6, 61.2) were observed in 13C
NMR and DEPT spectra. Analysis of 2D NMR data indicated that
the disaccharide unit was composed of two ꢀ-galactopyranose
moieties. The connectivity between the two sugar units was
determined on the basis of HMBC correlations from H-1′′′ (δH 4.43)
to C-6′′ (δC 68.6) and from H-6′′ (δH 3.97 and 3.93) to C-1′′′ (δC
103.9). The (1f6)-linkage was confirmed by the 1H NMR spectrum
(in DMSO-d6) that revealed six doublet signals and only one triplet
signal due to OH protons. HMBC correlation from H-1′′ (δH 4.89)
and the specific rotation ([R]25 +71.6, c 0.05, H2O, 24 h) of the
D
aqueous layer of the hydrolysate were identical to those of known
* To whom correspondence should be addressed. Tel: +66-25646700,
ext. 3553. Fax: +66-25646707. E-mail: taridaporn@biotec.or.th.
10.1021/np070689m CCC: $40.75
2008 American Chemical Society and American Society of Pharmacognosy
Published on Web 03/26/2008

892 Journal of Natural Products, 2008, Vol. 71, No. 5
Table 1. Biological Activities of Compounds 1-4a
Notes
cytotoxicity, IC50 (µM)
BC cells NCI-H187 cells
compound
antimalaria, IC50 (µM)
anti-HSV-1, IC50 (µM)
KB cells
Vero cells
1
2
>10
7.2 ( 2.1
>50
>25
4.4 ( 1.3
20.2 ( 2.5
8.8 ( 1.8
>50
13.9 ( 1.6
>25
13.6 ( 1.9
>50
43.2 ( 4.3
32.1 ( 3.6
34.3 ( 1.3
>100
>10
>25
3 (KS-501a)
4
9.9 ( 0.9
>25
0.0039 ( 0.0003
>100
13.0 ( 1.2
>50
>100
dihydroartemisininb
acyclovirc
ellipticined
10.2 ( 3.6
1.99 ( 0.23
0.49 ( 0.12
1.71 ( 0.19
1.94 ( 0.13
a The IC50 values are given as the mean ( SD (n ) 3). b Standard antimalarial compound. c Standard compound for antiherpes simplex virus type 1
(HSV-1) assay. d Standard compound for cytotoxicity assays against oral human epidermal carcinoma (KB), human breast cancer (BC), human
small-cell lung cancer (NCI-H187), and African green monkey kidney fibroblast (Vero) cells.
out following the condition described previously.17 PCR products
to C-2 (δC 156.8) indicated attachment of the digalactopyranose
were purified with a QIAquick PCR purification kit (QIAGEN) and
sequenced by Macrogen Inc., Korea. Phylogenetic analysis of the
sequence data using BioEdit 7.0.5 and PAUP programs combined
with morphological data indicated that BCC 14080 belongs to the
genus Acremonium. The fungus sequence was submitted to GenBank
with accession number EU488735.
moiety to C-2 of the aglycone. Analysis of the acid hydrolysate of
2 yielded D-galactopyranose as the only sugar. The methanolysis
of 2 also yielded its aglycone (3), which was spectroscopically
identical to KS-501a11 (51%), along with 5-heptylresorcinol12 (31%)
and methyl 2-heptyl-4,6-dihydroxybenzoate14 (34%).
Compound 3, the aglycone of compounds 1 and 2, was also
isolated as cometabolite from BCC 14080. Its spectroscopic data
were identical to those of KS-501a.11 KS-501a was previously
described as the synthetic product from methanolysis of its ꢀ-D-
galactofuranoside (KS-501), which was the secondary metabolite
of the fungus Sporothrix sp. KAC-1985.11 Herein, KS-501a is
reported as a naturally occurring substance.
Compound 4 has the molecular formula C20H32O7 as established
by HRMS (ESITOF). It consisted of a sugar unit connected to a
5-heptylresorcinol.12 The sugar unit of 4 was different from that
found in 1 and 2. The vicinal coupling constants of H-1′ to H-5′
(J1′,2′ ) 7.8 Hz, J2′,3′ ) 9.0 Hz, J3′,4′ ) 9.0 Hz, J4′,5′ ) 9.0 Hz)
confirmed that H-1′ to H-5′ were all oriented in the axial positions
of a pyranose ring. HMBC correlations observed from methoxy
protons (δH 3.54; 3H, s) to C-4′ (δC 79.4) and from H-4′ (δH 3.17;
1H, t, J ) 9.0 Hz) to a methoxy carbon (δC 59.7, 4′-OCH3) indicated
that the sugar unit was 4-O-methyl-ꢀ-glucopyranose. The con-
nectivity of this sugar unit to aglycone was deduced by HMBC
correlation from H-1′ (δH 4.83) to C-1 (δC 158.9). Acid hydrolysis
of 4 was not performed due to its small quantity; therefore, the
configuration of 4-O-methylglucopyranose was not determined.
All isolated compounds were screened for antimalarial, cytotoxic,
and anti-HSV-1 activities. Compound 1 displayed anti-HSV-1
activity with an IC50 value of 7.2 µM. Its aglycone, compound 3,
was active against malaria parasite Plasmodium falciparum K1 with
an IC50 value of 9.9 µM. Compounds 1-3 were cytotoxic against
BC cell lines with IC50 values of 4.4, 20.2, and 8.8 µM, respectively.
Cytotoxic activities against KB, NCI-H187, and nonmalignant Vero
cell lines are shown in Table 1. The phenolic glycoside (4) was
inactive against Plasmodium falciparum K1 (at 25 µM) and
noncytotoxic against three cancer cell lines (at 50 µM).
Fermentation, Extraction, and Isolation. The fungus BCC 14080
was cultured in 10 L (40 × 250 mL) of bacto-malt extract broth on
rotary shakers (200 rpm) for 32 days at 25 °C, and then the culture
was filtered. The filtrate was extracted twice with an equal volume
of EtOAc. The organic layer was concentrated under reduced
pressure to obtain a dark brown gum (2.12 g). The broth extract
was passed through a Sephadex LH-20 column (elution with 100%
MeOH) to afford eight fractions (1–8). Fraction 4 yielded pure
compound 2 (1.31 g). Fraction 6 was subjected to silica gel column
chromatography (step gradient elution with 0–15% MeOH/CHCl3)
to provide 14 subfractions (6-1–6-14). Fraction 6-9 was pure
compound 4 (4.7 mg). Compound 1 (9.2 mg) was obtained from
fraction 6-11 after further purification by preparative HPLC using
a reversed-phase column (Nova-Pak HR C18, 6 µm, 25 × 100 mm;
MeOH/H2O, 85:15).
The mycelial cakes were macerated with MeOH (1 L, 2 days)
and filtered. To the filtrate was added H2O (100 mL), and the mixture
was washed with hexane (700 mL). The aqueous MeOH layer was
concentrated under reduced pressure. The residue was dissolved in
EtOAc (700 mL) and washed with H2O (200 mL). The organic layer
was concentrated under reduced pressure to leave a pale yellow solid
(3.65 g). This mycelial extract was subjected to Sephadex LH-20
column chromatography (elution with 100% MeOH) to yield
compounds 2 (429 mg), and 3 (8.5 mg).
Compound 1: white solid; mp 174–176 °C; [R]27 –3.3 (c 0.10,
D
MeOH); UV (MeOH) λmax (log ε) 203 (4.66), 255 (3.87) nm; IR
(CHCl3) νmax 3423, 2926, 1728, 1613, 1592, 1465, 1260, 1073 cm-1
;
1H NMR (acetone-d6, 500 MHz) δ 6.70 (1H, t, J ) 2.1 Hz, H-2′),
6.68 (1H, d, J ) 2.1 Hz, H-3), 6.59 (2H, br m, H-4′ and H-6′), 6.49
(1H, d, J ) 2.1 Hz, H-5), 4.86 (1H, d, J ) 7.7 Hz, H-1′′), 3.96 (1H,
br d, J ) 3.3 Hz, H-4′′), 3.84 (1H, dd, J ) 9.4, 7.7 Hz, H-2′′), 3.83
(1H, dd, J ) 11.2, 6.2 Hz, H-6′′a), 3.78 (1H, dd, J ) 11.2, 5.1 Hz,
H-6′′b), 3.75 (1H, br dd, J ) 6.2, 5.1 Hz, H-5′′), 3.64 (1H, dd, J )
9.4, 3.3 Hz, H-3′′), 2.72 (1H, dt, J ) 13.4, 8.0 Hz, H-7a), 2.65 (1H,
dt, J ) 13.4, 8.0 Hz, H-7b), 2.56 (2H, t, J ) 7.9 Hz, H-7′), 1.62
(4H, m, H-8 and H-8′), 1.39-1.22 (16H, m, H-9-H-12 and H-9′-H-
12′), 0.87 (3H, t, J ) 7.0 Hz, H-13 or H-13′), 0.86 (3H, t, J ) 6.90
Hz, H-13′ or H-13); 13C NMR (acetone-d6, 125 MHz) δ 166.4 (C,
CdO), 159.8 (C, C-4), 158.2 (C, C-3′), 157.2 (C, C-2), 152.1 (C,
C-1′), 145.2 (C, C-5′), 143.3 (C, C-6), 115.5 (C, C-1), 112.8 (CH,
C-4′ or C-6′), 112.7 (CH, C-6′ or C-4′), 110.4 (CH, C-5), 106.8
(CH, C-2′), 103.0 (CH, C-1′′), 101.5 (CH, C-3), 75.7 (CH, C-5′′),
73.8 (CH, C-3′′), 71.4 (CH, C-2′′), 69.0 (CH, C-4′′), 61.5 (CH2,
C-6′′), 35.5 (CH2, C-7′), 33.6 (CH2, C-7), 31.7 (CH2, C-11 and
C-11′), 31.4 (CH2, C-8′ or C-8), 31.1 (CH2, C-8 or C-8′), 29.4 and
29.0 (CH2, C-9, C-10, C-9′, and C-10′), 22.4 (CH2, C-12 and C-12′),
13.5 (CH3, C-13 and C-13′); HRMS (ESITOF) m/z 627.3152 [M +
Na]+ (calcd for C33H48O10Na, 627.3145).
Experimental Section
General Experimental Procedures. Melting points were measured
on an Electrothermal IA9100 digital melting point apparatus. Optical
rotations were conducted by using a JASCO P-1030 digital
polarimeter. UV and IR spectra were recorded on a Varian Cary 1E
UV–vis spectrophotometer and a Bruker VECTOR 22 spectrometer,
respectively. NMR spectra were taken on a Bruker AV500D
spectrometer. ESITOF mass spectra were recorded on a Micromass
LCT spectrometer.
Fungal Material. The fungus Acremonium sp. was collected on
a palm leaf from Khao Yai National Park, Nakhon Ratchasima
Province, and isolated by Mr. Prasert Srikitikulchai. This fungus
was deposited at the BIOTEC Culture Collection as BCC 14080 on
September 12, 2003. Genomic DNA of BCC 14080 was extracted
from lyophilized mycelia (50–100 mg) by CTAB method.15 The
ITS1-5.8S-ITS2 region of rDNA sequences was amplified using the
universal primers ITS4 and ITS5.16 PCR amplification was carried
Compound 2: pale yellow solid; mp 200–202 °C; [R]26 –10.6
D
(c 0.20, MeOH); UV (MeOH) λmax (log ε) 203 (5.10), 253 (4.26)
nm; IR (CHCl3) νmax 3406, 2926, 1725, 1620, 1590, 1465, 1259,
1076 cm-1; 1H NMR (acetone-d6/D2O, 95:5, 500 MHz) δ 6.92 (1H,

Notes
Journal of Natural Products, 2008, Vol. 71, No. 5 893
d, J ) 2.1 Hz, H-3), 6.65 (1H, t, J ) 2.1 Hz, H-2′), 6.58 (1H, br m,
H-4′), 6.52 (1H, br m, H-6′), 6.43 (1H, d, J ) 2.1 Hz, H-5), 4.89
(1H, d, J ) 7.7 Hz, H-1′′), 4.43 (1H, d, J ) 7.7 Hz, H-1′′′), 4.05
(1H, br dd, J ) 7.0, 5.2 Hz, H-5′′), 3.97 (1H, dd, J ) 11.7, 7.0 Hz,
H-6′′a), 3.94 (1H, br d, J ) 3.5 Hz, H-4′′), 3.93 (1H, dd, J ) 11.7,
5.2 Hz, H-6′′b), 3.88 (1H, br d, J ) 3.4 Hz, H-4′′′), 3.82 (1H, dd,
J ) 9.5, 7.7 Hz, H-2′′), 3.77 (1H, dd, J ) 11.2, 6.9 Hz, H-6′′′a),
3.72 (1H, dd, J ) 11.2, 5.2 Hz, H-6′′′b), 3.65 (1H, dd, J ) 9.5, 3.5
Hz, H-3′′), 3.59 (1H, dd, J ) 9.7, 7.7 Hz, H-2′′′), 3.55 (1H, br dd,
J ) 6.9, 5.2 Hz, H-5′′′), 3.52 (1H, dd, J ) 9.7, 3.4 Hz, H-3′′′), 2.66
(2H, m, H-7), 2.54 (2H, t, J ) 8 Hz, H-7′), 1.62 (2H, m, H-8), 1.60
(2H, m, H-8′), 1.40-1.22 (16H, m, H-9-H-12 and H-9′-H-12′),
0.85 (6H, t, J ) 7.0 Hz, H-13 and H-13′); 1H NMR (DMSO-d6, 500
MHz,) δ 9.73 (1H, s, 4-OH), 9.56 (1H, s, 3′-OH), 6.65 (1H, d, J )
1.7 Hz, H-3), 6.51 (1H, br s, H-4′), 6.48 (1H, t, J ) 1.9 Hz, H-2′),
6.43 (1H, br s, H-6′), 6.34 (1H, d, J ) 1.7 Hz, H-5), 5.13 (1H, d,
J ) 4.6 Hz, 2′′′-OH), 4.93 (1H, d, J ) 5.9 Hz, 3′′-OH), 4.81 (1H,
d, J ) 7.8 Hz, H-1′′), 4.80 (1H, d, J ) 5.6 Hz, 2′′-OH), 4.75 (1H,
d, J ) 5.6 Hz, 3′′′-OH), 4.65 (1H, d, J ) 4.8 Hz, 4′′-OH), 4.60
(1H, t, J ) 5.6 Hz, 6′′′-OH), 4.51 (1H, d, J ) 4.7 Hz, 4′′′-OH),
4.19 (1H, d, J ) 7.6 Hz, H-1′′′), 3.84 (2H, m, H-5′′ and H-6′′a),
3.74 (1H, t, J ) 4.0 Hz, H-4′′), 3.67 (1H, dd, J ) 12.2, 8.2 Hz,
H-6′′b), 3.62 (1H, t, J ) 3.8 Hz, H-4′′′), 3.57 (1H, ddd, J ) 9.2,
7.8, 5.6 Hz, H-2′′), 3.51 (1H, ddd, J ) 11.0, 5.6, 5.1 Hz, H-6′′′a),
3.48 (1H, ddd, J ) 11.0, 5.6, 5.2 Hz, H-6′′′b), 3.42 (1H, ddd, J )
9.2, 5.9, 4.0 Hz, H-3′′), 3.34 (2H, m, H-2′′′ and H-5′′′), 3.26 (1H,
ddd, J ) 9.3, 5.6, 3.8 Hz, H-3′′′), 2.57 (2H, m, H-7), 2.50 (2H, m,
H-7′), 1.53 (4H, m, H-8 and H-8′), 1.28-1.23 (16H, m, H-9–H-12
and H-9′–H-12′), 0.85 (3H, t, J ) 6.8 Hz, H-13 or H-13′), 0.84
(3H, t, J ) 7.3 Hz, H-13′ or H-13); 13C NMR (acetone-d6/D2O,
95:5, 125 MHz) δ 166.6 (C, CdO), 159.8 (C, C-4), 158.2 (C, C-3′),
156.8 (C, C-2), 152.0 (C, C-1′), 145.1 (C, C-5′), 143.1 (C, C-6),
114.6 (C, C-1), 112.9 (CH, C-4′), 112.4 (CH, C-6′), 110.2 (CH,
C-5), 106.7 (CH, C-2′), 103.9 (CH, C-1′′′), 102.1 (CH, C-1′′), 101.1
(CH, C-3), 75.2 (CH, C-5′′′ or C-5′′), 74.9 (CH, C-5′′ or C-5′′′),
73.4 (CH, C-3′′ or C-3′′′), 73.3 (CH, C-3′′′ or C-3′′), 71.7 (CH,
C-2′′′), 71.3 (CH, C-2′′), 68.9 (CH, C-4′′′ or C-4′′), 68.7 (CH, C-4′′
or C-4′′′), 68.6 (CH2, C-6′′), 61.2 (CH2, C-6′′′), 35.5 (CH2, C-7′),
33.6 (CH2, C-7), 31.7 (CH2, C-11 or C-11′), 31.6 (CH2, C-11′ or
C-11), 31.4 (CH2, C-8′), 31.1 (CH2, C-8), 29.4 and 29.0 (CH2, C-9,
C-10, C-9′, and C-10′), 22.4 (CH2, C-12 and C-12′), 13.5 (CH3,
C-13 and C-13′); HRMS (ESITOF) m/z 789.3688 [M + Na]+ (calcd
for C39H58O15Na, 789.3673).
Figure 1. Selected NOESY (dashed lines) and HMBC (solid lines)
correlations for compound 2.
concentrated in Vacuo to yield an anomeric mixture of D-galactose
(23.7 mg; [R]27 +89.6, c 1.2, H2O, 24 h). The organic layer was
D
concentrated and purified by a Sephadex LH-20 column (elution
with 100% MeOH) to obtain 5-heptylresorcinol12 (24.0 mg).
Methanolysis of 2. Anhydrous HCl gas was bubbled through
MeOH (15 mL) for 15 min. Compound 2 (200.0 mg) was dissolved
in HCl/MeOH (5 mL) and then heated to 70 °C for 12 h. The reaction
mixture was diluted with H2O (10 mL) and extracted with EtOAc
(3 × 15 mL). The organic layer was evaporated to dryness, and the
residue was purified by silica gel column chromatography (step
gradient elution with 0–20% MeOH/CHCl3) to obtain compound 3
(59.4 mg), 5-heptylresorcinol12 (17.0 mg), and methyl 2-heptyl-
4,6-dihydroxybenzoate14 (23.4 mg).
Biological Assays. Antimalarial activity against Plasmodium
falciparum K1 was evaluated by using microculture radioisotope
technique.18 Antiherpes simplex virus type 1 (HSV-1) assay and
cytotoxicity assays against oral human epidermal carcinoma (KB)
cells, human breast cancer (BC) cells, human small-cell lung cancer
(NCI-H187) cells, and African green monkey kidney fibroblast
(Vero) cells were carried out by employing a colorimetric method.19,20
Acknowledgment. We thank Mr. R. Ridkaew for his valuable
suggestion concerning the fungal identification. Financial support from
the Bioresources Research Network, National Center for Genetic
Engineering and Biotechnology (BIOTEC), is gratefully acknowl-
edged.
Compound 4: pale yellow solid; mp 132–134 °C; [R]26 –47.3
References and Notes
D
(c 0.05, MeOH); UV (MeOH) λmax (log ε) 203 (4.86), 219 (4.35),
269 (4.01) nm; IR (CHCl3) νmax 3384, 2926, 1622, 1594, 1465, 1309,
1178, 1093, 1057 cm-1; 1H NMR (acetone-d6/D2O, 95:5, 500 MHz,)
δ 6.39 (1H, t, J ) 2.2 Hz, H-2), 6.35 (1H, br d, J ) 2.2 Hz, H-6),
6.32 (1H, br d, J ) 2.2 Hz, H-4), 4.83 (1H, d, J ) 7.8 Hz, H-1′),
3.81 (1H, dd, J ) 12.0, 2.1 Hz, H-6′a), 3.66 (1H, dd, J ) 12.0, 5.1
Hz, H-6′b), 3.59 (1H, t, J ) 9.0 Hz, H-3′), 3.54 (3H, s, 4′-OCH3),
3.42 (1H, ddd, J ) 9.0, 5.1, 2.1 Hz, H-5′), 3.41 (1H, dd, J ) 9.0,
7.8 Hz, H-2′), 3.17 (1H, t, J ) 9.0 Hz, H-4′), 2.45 (2H, t, J ) 7.5
Hz, H-7), 1.54 (2H, quin, J ) 7.5 Hz, H-8), 1.22–1.35 (8H, m,
H-9–H-12), 0.85 (3H, t, J ) 7.0 Hz, H-13); 13C NMR (acetone-d6/
D2O, 95:5, 125 MHz) δ 158.9 (C, C-1), 158.3 (C, C-3), 144.9 (C,
C-5), 109.2 (CH, C-4), 107.7 (CH, C-6), 101.1 (CH, C-2), 100.7
(CH, C-1′), 79.4 (CH, C-4′), 76.9 (CH, C-3′), 75.9 (CH, C-5′), 73.9
(CH, C-2′), 61.1 (CH2, C-6′), 59.7 (CH3, 4′-OCH3), 35.7 (CH2, C-7),
31.7 (CH2, C-11), 31.1 (CH2, C-8), 29.0 (CH2, C-9 and C-10), 22.4
(CH2, C-12), 13.4 (CH3, C-13); HRMS (ESITOF) m/z 407.2044 [M
+ Na]+ (calcd for C20H32O7Na, 407.2046).
(1) Evans, L.; Hedger, J. N.; Brayford, D.; Stavri, M.; Smith, E.;
O’Donnell, G.; Gray, A. I.; Griffith, G. W.; Gibbons, S. Phytochemistry
2006, 67, 2110–2114.
(2) Strobel, G. A.; Torczynski, R.; Bollon, A. Plant Sci. 1997, 128, 97–
108.
(3) Ahn, J. S.; Kim, B. Y.; Oh, W. K.; Mheen, T. I.; Ahn, S. C.; Kang,
D. O.; Ko, H. R.; Kim, H. M. WO 0146385, 2001.
(4) Aoki, K.; Uchiyama, R.; Itonori, S.; Sugita, M.; Che, F.-S.; Isogai,
A.; Hada, N.; Hada, J.; Takeda, T.; Kumagai, H.; Yamamoto, K.
Biochem. J. 2004, 378, 461–472.
(5) Chen, C.; Imamura, N.; Nishijima, M.; Adachi, K.; Sakai, M.; Sano,
H. J. Antibiot. 1996, 49, 998–1005.
(6) Boot, C. M.; Amagata, T.; Tenney, K.; Compton, J. E.; Pietraszkiewicz,
H.; Valeriote, F. A.; Crews, P. Tetrahedron 2007, 63, 9903–9914.
(7) Nakai, R.; Ogawa, H.; Asai, A.; Ando, K.; Agatsuma, T.; Matsumiya,
S.; Akinaga, S.; Yamashita, Y.; Mizukami, T. J. Antibiot. 2000, 53,
294–296.
(8) Kleinwachter, P.; Schlegel, B.; Dorfelt, H.; Grafe, U. J. Antibiot. 2001,
54, 526–527.
(9) Sassa, T.; Ooi, T.; Kinoshita, H. Biosci. Biotechnol. Biochem. 2004,
68, 2633–2636.
(10) (a) Bunyapaiboonsri, T.; Yoiprommarat, S.; Intereya, K.; Kocharin,
K. Chem. Pharm. Bull. 2007, 55, 304–307. (b) Isaka, M.; Kittakoop,
P.; Kirtikara, K.; Hywel-Jones, N. L.; Thebtaranonth, Y. Acc. Chem.
Res. 2005, 38, 813–823.
Hydrolysis of 1. Compound 1 (4.0 mg) was hydrolyzed with 5%
HCl (1 mL) at 90 °C for 12 h. The reaction mixture was then diluted
with H2O (3 mL) and extracted with EtOAc (3 × 5 mL). The aqueous
layer was concentrated in Vacuo to yield an anomeric mixture of
D-galactose (0.98 mg; [R]25D +71.6, c 0.05, H2O, 24 h). The specific
rotation, [R]25 +79.0 (c 1.0, H2O, 24 h), was observed for an
(11) (a) Yasuzawa, T.; Saitoh, Y.; Sano, H. J. Antibiot. 1990, 43, 336–
343. (b) Nakanishi, S.; Toki, S.; Kase, H.; Matsuda, Y.; Shiozaki, S.;
Shuto, K.; Ikeda, J.; Kubo, K. Jpn. Kokai Tokkyo Koho JP 02256619,
1990.
(12) Arisawa, M.; Ohmura, K.; Kobayashi, A.; Morita, N. Chem. Pharm.
Bull. 1989, 37, 2431–2434.
(13) (a) Anker, R. M.; Cook, A. H. J. Chem. Soc. 1945, 311–313. (b)
Huneck, S.; Schmidt, J.; Tabacchi, R. Z. Naturforsch., B: Chem. Sci.
1989, 44, 1283–1289.
D
anomeric mixture of D-galactose standard. The organic layer was
evaporated to dryness and then purified by a Sephadex LH-20
column (elution with 100% MeOH) to obtain pure compound (2.5
mg), whose MS and 1H NMR spectra were identical to the literature
data of 5-heptylresorcinol.12
Hydrolysis of 2. Hydrolysis of compound 2 (65.0 mg) was
performed in the same manner as 1. The aqueous layer was

894 Journal of Natural Products, 2008, Vol. 71, No. 5
Notes
(14) Djura, P.; Sargent, M. V. Aust. J. Chem. 1976, 29, 899–906.
(15) White, T. J.; Bruns, T. D.; Lee, S.; Taylor, J. W. In PCR Protocols:
A Guide to Methods and Applications; Innis, M. A.; Gelfand, D. H.;
Sninsky, J. J.; White, T. J., Eds.; Academic Press: San Diego, 1990;
pp 315–322.
(16) Luangsa-ard, J. J.; Hywel-Jones, N. L.; Manoch, L.; Samson, R. A.
Mycol. Res. 2005, 109, 581–589.
(18) Desjardins, R. E.; Canfield, C. J.; Haynes, J. D.; Chulay, J. D.
Antimicrob. Agents Chemother. 1979, 16, 710–718.
(19) Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.;
Vistica, D.; Warren, J. T.; Bokesch, H.; Kenney, S.; Boyd, M. R.
J. Natl. Cancer Inst. 1990, 82, 1107–1112.
(20) Plumb, J. A.; Milroy, R.; Kaye, S. B. Cancer Res. 1989, 49,
4435–4440.
(17) O’Donnell, K.; Cigelnik, E.; Weber, N. S.; Trappe, J. M. Mycologia
1997, 89, 48–65.
NP070689M