Cytotoxic dihydrothiophene-condensed chromones from the marine-derived fungus penicillium oxalicum

Article abstract of DOI:10.1055/s-0033-1350805

Two new dihydrothiophene-condensed chromones and a new natural chromone, namely oxalicumones A-C (1-3), respectively, were isolated from a culture broth of a marine-derived fungus, Penicillium oxalicum. The structures of 1-3 and acetylated derivatives of 1 (4-7) were elucidated on the basis of spectroscopic methods and chemical reactions. The absolute configuration of 1 and 2 were established by using the modified Mosher ester method and circular dichroism data of an in situ formed [Rh₂(OCOCF₃)₄] and [Mo₂(OAc)₄] complex. (R)-MTPA ester of 1 showed cytotoxicity against A375, SW-620, and HeLa carcinoma cell lines with IC ₅₀ values of 8.9, 7.8, and 18.4 M, respectively. Compound 1 displayed cytotoxicity against A375 and SW-620 cell lines with IC₅₀ values of 11.7 and 22.6 M, respectively. The structure-biological activity relationship of 1 was discussed. Georg Thieme Verlag KG Stuttgart.

Full text of DOI:10.1055/s-0033-1350805

1474 Letters
Key words
Penicillium oxalicum
·
Trichocomaceae
·
dihydrothio-
Cytotoxic Dihydrothiophene-
phene‑condensed chromone · cytotoxicity
Condensed Chromones from the
Marine-Derived Fungus Penicillium
oxalicum
Supporting information available online at
http://www.thieme-connect.de/ejournals/toc/plantamedica
Yu-Lin Sun1,3, Jie Bao1,3, Kai-Sheng Liu2, Xiao-Yong Zhang1,
Fei He1, Yi-Fei Wang2, Xu-Hua Nong1,3, Shu-Hua Qi1
Gorgonian corals are known to produce novel acetogenins, ses-
quiterpenoids, diterpenoids, prostanoids, and steroids with vari-
ous bioactivities such as antitumor, antituberculosis, anti-inflam-
mation, and antioxidant effects [1,2]. It is thought that maybe
gorgonian-associated microorganisms are the true producers of
some of their host-derived compounds [3]. Recently, there were
a few reports about the secondary metabolites of gorgonian-as-
sociated microorganisms [4–9]. The fungus Penicillium oxalicum
SCSGAF 0023 strain (Trichocomaceae) was isolated from the
South China Sea gorgonian Muricella flexuosa, and identified by
Zhang et al. [10]. Previous chemical investigations on P. oxalicum
led to the isolation of some biologically active and structurally
novel secondary metabolites [11–14]. During the course of our
investigation on the secondary metabolites of the P. oxalicum
SCSGAF 0023 strain, two new dihydrothiophene-condensed
chromones, oxalicumones A and B (1, 2), and a new natural chro-
1
Key Laboratory of Marine Bio-resources Sustainable Utilization/
Guangdong Key Laboratory of Marine Materia Medica/RNAM
Center for Marine Microbiology, South China Sea Institute of
Oceanology, The Chinese Academy of Sciences, Guangzhou,
Guangdong, P.R. China
Jinan University, Guangzhou, Guangdong, P.R. China
Graduate School of the Chinese Academy of Sciences, Beijing,
2
3
P.R. China
Abstract
!
Two new dihydrothiophene-condensed chromones and a new
natural chromone, namely oxalicumones A–C (1–3), respectively,
were isolated from a culture broth of a marine-derived fungus,
Penicillium oxalicum. The structures of 1–3 and acetylated deriv-
atives of 1 (4–7) were elucidated on the basis of spectroscopic
methods and chemical reactions. The absolute configuration of 1
and 2 were established by using the modified Mosher ester
method and circular dichroism data of an in situ formed [Rh2
(OCOCF3)4] and [Mo2(OAc)4] complex. (R)-MTPA ester of 1
showed cytotoxicity against A375, SW-620, and HeLa carcinoma
cell lines with IC50 values of 8.9, 7.8, and 18.4 µM, respectively.
Compound 1 displayed cytotoxicity against A375 and SW-620
cell lines with IC50 values of 11.7 and 22.6 µM, respectively. The
structure–biological activity relationship of 1 was discussed.
"
mone (3) [15] (l Fig. 1) were isolated from a culture broth of the
fungal strain. Although chromones are naturally occurring com-
pounds (polyketides) widely found in plants and fungi [16], a di-
hydrothiophene-condensed chromone core is rare in natural
products or synthetic compounds [17].
The molecular formula of 1 was determined to be C19H20O9S by
HRESIMS (m/z 447.0693 [M + Na]+) and NMR spectra. The 1H
"
NMR spectrum (l Table 1) showed characteristic signals for two
aromatic protons at δH 6.63 (s), 6.72 (s), two methoxy groups at
δ
H 3.84 (s), 3.89 (s), one tertiary methyl at δH 2.39 (s), two meth-
ylenes at δH 2.94, 3.04, 3.14, 3.38 (each 1H), two methines at δH
4.45, 4.13, and one phenolic hydroxyl proton at δH 12.06. The 13
C
"
and DEPT NMR spectral data (l Table 2) indicated that 1 con-
Fig. 1 Structures of 1–9. (Color figure available online only.)
Sun Y-L et al. Cytotoxic Dihydrothiophene-Condensed Chromones… Planta Med 2013; 79: 1474–1479

Letters 1475
Table 1 1H NMR data of compounds 1, 2, and 4–7 in CDCl3.
no.
δ,a mult (Jb)
1
2
4
5
6
7
2
4
6
7
6.63, s
6.64, s
7.17, s
7.16, s
6.66, s
6.64, s
6.73, s
6.72, s
6.73, s
6.84, s
6.84, s
6.73, s
4.13, dd (8.0, 9.0)
3.14, dd (9.0, 17.5)
3.38, dd (8.0, 17.5)
2.94, dd (6.0, 14.5)
3.04, dd (3.5, 14.5)
4.45, dd (3.0, 6.0)
3.84, s
3.91, dd (9.5, 9.2)
2.93, dd (9.8, 17.3)
3.34, dd (9.2, 17.3)
3.00, dd (5.5, 14.0)
3.36, dd (3.8, 14.1)
4.53, dd (5.5, 3.9)
3.81, s
3.96, dd (8.3, 8.4)
3.12, dd (8.6, 17.2)
3.17, dd (8.1, 17.2)
3.01, dd (7.6, 14.5)
3.08, dd (4.3, 14.5)
5.22, dd (4.3, 7.6)
3.78, s
4.33, dd (4.6, 7.8)
4.42, dd (4.3, 7.8)
3.20, dd (4.3, 17.7)
3.63, dd (7.8, 17.7)
3.02, d (6.0)
3.04, d (6.0)
5.21, dd (5.8, 6.2)
3.77, s
4.01, dd (8.3, 8.6)
3.13, dd (8.3, 17.7)
3.35, dd (8.6, 17.7)
3.02, d (7.5)
3.07, d (4.5)
5.24, dd (4.5, 7.5)
3.79, s
3.17, dd (4.6, 17.4)
3.57, dd (7.8, 17.4)
12
2.99, d (5.7)
3.00, d (6.6)
13
5.18, dd (5.6, 6.6)
Me-16
Me-17
Me-18
-OOCMe
3.78, s
3.80, s
2.45, s
2.17, S
2.19, S
2.40, S
–
3.89, s
3.84, s
3.86, s
3.84, s
3.90, s
2.39, s
2.40, s
2.45, s
2.41, s
2.40, s
–
–
2.18, s
2.19, s
2.19, s
2.38, s
2.23, s
13-OH
11-OH
1-OH
–
4.33, br s
–
–
–
–
–
4.06, br s
–
–
4.09, br s
12.04, s
12.06, s
12.02, s
–
–
12.21, s
a 500 M Hz; b coupling constants in Hz
No.
δ,a Cb
Table 2 13 C NMR data of com-
pounds 1, 2, 4, and 5 in CDCl3.
1
2
4
5
1
160.8, C
113.0, CH
147.2, C
107.8, CH
157.1, C
50.7, CH
37.9, CH2
178.8, C
109.1, C
120.5, C
171.0, C
79.6, C
160.8, C
113.0, CH
147.2, C
107.9, CH
157.1, C
52.1, CH
37.1, CH2
179.5, C
109.0, C
119.9, C
169.6, C
86.2, C
149.3, C
121.1, CH
145.1, C
117.5, CH
158.0, C
50.2, CH
37.6, CH2
173.3, C
116.3, C
117.5, C
167.2, C
80.0, C
149.3, C
121.3, CH
145.1, C
115.5, CH
157.7, C
49.9, CH
39.7, CH2
174.7, C
115.5, C
117.6, C
168.7, C
86.2, C
2
3
4
4a
6
7
8
8a
9
10
11
12
35.4, CH2
71.2, CH
173.1, C
173.4, C
53.0, CH3
53.7, CH3
22.3, CH3
36.8, CH2
70.7, CH
172.2, C
173.3, C
52.9, CH3
53.1, CH3
22.3, CH3
32.2, CH2
72.0, CH
168.7, C
172.4, C
52.7, CH3
53.8, CH3
20.6, CH3
21.1, 21.7
170.0, 171.8
29.7, CH2
72.1, CH
169.6, C
169.8, C
52.7, CH3
53.4, CH3
20.5, CH3
13
14
15
16
17
18
-OOCMe
-OOCMe
21.6, 21.4, 21.2
170.0, 170.1, 170.1
a 125 M Hz; b Assignments by edited gs-HSQC experiments
tained 19 carbons, including three methyls, two methylenes, four
methines, and ten quaternary carbons. These data suggested that
1 contained a 1-hydroxy-3-methylchromone core [18–20].
Fig. 2 Key HMBC and
1H-1H COSY correla-
tions for 1.
"
This suggestion was proved by the HMBC spectrum (l Fig. 2),
which showed correlations from H-2 to C-1/C-3/C-4/C-8a/C-18,
from H-4 to C-2/C-3/C-4a/C-8a/C-18, and from Me-18 to C-2/C-
3/C-4. In addition, correlations from H-7 [δH 3.14 (1H, dd, J = 9.0,
17.5 Hz), 3.38 (1H, dd, J = 8.0, 17.5 Hz)] to C-6 (δC 52.1)/C‑10 (δC
171.0)/C‑9 (δC 120.5) in the HMBC spectrum and a correlation
from H-7 to H-6 [δH 4.13 (1H, dd, J = 8.0, 9.0 Hz)] in the 1H-1H
"
COSY spectrum (l Fig. 2), combined with the molecular formula
C19H20O9S and chemical shifts of H-7, H-6, C-7 (δC 37.9), and C-6,
indicated the presence of a five-membered ring containing a sul-
Sun Y-L et al. Cytotoxic Dihydrothiophene-Condensed Chromones… Planta Med 2013; 79: 1474–1479

1476 Letters
Fig. 3 Δδ (δS – δR) val-
ues in ppm for MTPA
esters of 1.
fur atom (2,3-dihydrothiophene unit) connected with the 1-hy-
droxy-3-methylchromone core. Further comparison of the 1H
and 13C NMR data of 1 with those of coniothienol A [17] sug-
gested that 1 had the same dihydrothiophene-condensed chro-
mone skeleton. Coniothienol A (8), preussochromone A [21], and
coniothiepinols A and B [17] were isolated from fungi and have
similar chromone structures with a sulfur atom placed at the
same position. In this study, we also obtained coniochaetone B
(9) [22] (a known chromone) and oxalicumone C (3) (a new nat-
ural chromone) [15]. From their structural analysis, we conjec-
tured that coniochaetone B derived from 3, and preussochro-
mone A, coniothiepinols A and B, coniothienol A, and 1 had sim-
ilar biogenetic pathways to form the thiophene-condensed chro-
mone, thiopyran-condensed chromone, or thiepinol skeletons.
So, we inferred that the sulfur atom in 1 should be located at po-
sition-5 instead of position-7. X‑ray data would be strong evi-
dence for the structure inferred, but unfortunately we failed to
obtain a crystal of 1. Furthermore, HMBC correlations from H-6
to C-7/C‑11/C‑12/C-15, from H-7 to C-6/C‑11, from H-12 to C-6/
C‑11/C‑13/C-14/C-15, from H-13 to C-11/C-12/C-14, from Me-16
to C-15, from Me-17 to C-14, and 1H-1H COSY correlation of H-12
with H-13, suggested a 2,4-dihydroxy-1,5-pentanedioic acid di-
methyl ester unit connected with the dihydrothiophene unit by
a C6-C11 bond.
Fig. 4 CD spectrum of 1 in CH2Cl2.
Fig. 5 CD spectrum of Rh-complex of 1b with the inherent CD spectrum
subtracted.
The absolute stereochemistry of 1 was further determined using
a modified Mosher ester NMR method [23]. Compound 1 was
treated separately with (S)-(+)- and (R)-(−)-α-methoxy-α-(tri-
fluoromethyl) phenylacetyl chloride (MTPA‑Cl) in dry pyridine
to yield the (R)- and (S)-MTPA ester derivatives 1a and 1b, respec-
tively. The shifted signals (H-6, H-7, H-12, and H-17) of the dia-
stereomeric MTPA esters (1a and 1b) were clearly different, and
"
the observed chemical shift differences (ΔδS‑R, l Fig. 3) unambig-
uously indicated the absolute configuration of C-13 in 1 to be R.
The 6S absolute configuration was proved by the CD data of 1
"
(l Fig. 4) that showed negative Cotton effects at around 300 to
350 nm, similar to those of coniothienol A [17]. The absolute con-
figuration of C-11 tertiary alcohol in 1 was assigned via the CD
data of the in situ formed [Rh2(OCOCF3)4] complex of 1b (MTPA
ester of 1), with the inherent contribution subtracted. According
to the bulkiness rule [24,25], the Rh-complex of 1b showed a pos-
"
itive E band at ca. 350 nm (l Fig. 5), revealing the 11S absolute
configuration in 1b and 1. In order to further verify the result,
the absolute configuration of the tert/sec 11,13-diol moiety in 1
was assigned using the in situ dimolybdenum CD method [26,
27]. Upon addition of dimolybdenum tetraacteate [Mo2(OAc)4]
to 1 in DMSO solution, a metal complex was generated as an aux-
iliary chromophore. The observed sign of the Cotton effect in the
induced spectrum originated solely from the chirality of the 1,3-
diol moiety expressed by the sign of the O−C−C−C−O torsion an-
Fig. 6 CD spectrum of 1 in DMSO containing Mo2(OAc)4 with the inherent
CD spectrum subtracted.
observed at around 400 nm. Based on the empirical rule pro-
posed by Frelek [26,27], two absolute configurations of
(11S,13R) and (11R,13S) could be deduced. Because the 13R abso-
"
gle. In the experiment (l Fig. 6), the negative Cotton effect was
Sun Y-L et al. Cytotoxic Dihydrothiophene-Condensed Chromones… Planta Med 2013; 79: 1474–1479

Letters 1477
Table 3 Cytotoxicity of 1–7 and 1a against several cell lines.
Compound
Cell-lines (IC50 µM)
A375
A549
HeLa
HepG2
SW-620
L-02
99.0 4.2
> 442.0
1
11.7 0.9
27.8 2.2
> 571.0
41.9 2.8
149.3 7.8
> 571.0
46.2 3.4
60.9 6.1
> 571.0
77.8 4.5
22.6 1.5
40.6 3.2
423 6.2
228.5 4.7
42.7 2.6
111.0 4.1
82.2 3.3
7.8 0.5
2
–
3
–
–
> 391.0
> 357.0
–
4
82.5 5.1
35.6 3.3
125.2 4.1
76.2 3.6
8.9 0.8
281.5 6.7
234.5 6.3
–
268.7 7.1
119.4 8.4
196.8 4.1
–
–
5
–
6
–
7
–
–
–
1a
33.4 1.5
5.5 0.2
18.4 1.2
9.3 0.4
–
35.0 1.1
Cisplatin
7.3 0.8
13.6 2.0
30.0 4.1
–
“–” Means no test; purity of 1–7 and 1a is ≥ 98%; cisplatin was bought from J&K Scientific Ltd., and its purity is 99%
lute configuration in 1 was determined by a modified Mosher es-
ter NMR method, the 11S absolute configuration was further con-
firmed. Thus, the 6S,11S,13R absolute configuration was deduced
for 1; its structure was determined to be as shown, and the com-
pound was named oxalicumone A.
Compound 2 had the same molecular formula of C19H20O9S as
oxalicumone A (1), which was determined by its (+)-ESIMS (m/z
447.08 [M + Na]+) and NMR spectra. The 1H and 13C NMR spectral
data of 2 showed great similarities to those of 1 with the only ob-
vious difference of the downfield shift of C-11 (from δC 79.6 in 1
to δC 86.2 in 2). Detailed analysis of the HMBC spectrum of 2
proved that 2 had the same plane structure as 1. The absolute
stereochemistry of 2 was further determined by using the modi-
fied Mosher ester method and circular dichroism data of in situ
formed [Rh2(OCOCF3)4] and [Mo2(OAc)4] complexes.
trum originated solely from the chirality of the 1,3-diol moiety
expressed by the sign of the O−C−C−C−O torsion angle. In the ex-
periment (see Supporting Information Fig. S38), the negative
Cotton effect was observed at around 400 nm. Based on the em-
pirical rule proposed by Frelek [24,25], two absolute configura-
tions of (11S,13R) and (11R,13S) were permitted deduction. Be-
cause the 11S absolute configuration in 2 was determined, the
13R absolute configuration in 2 was further confirmed. Thus, the
6R,11S,13R absolute configuration was deduced for 2; the struc-
ture of 2 was determined to be as shown, and the compound was
named oxalicumone B.
Compound 3 exhibited the molecular formula C17H18O8 as de-
1
duced from NMR data and ESIMS. Comparison of the H and 13C
NMR spectral data between 1 and 3 suggested that 3 also had a 1-
hydroxy-3-methylchromone core. Furthermore, in the HMBC
spectrum of 3, correlations from H-15 to C-7 (δC 167.0)/C-8 (δC
118.2)/C‑9 (δC 181.6)/C-16 (δC 173.1), and from Me-17 to C-16,
suggested a 2-hydroxyl methyl acetate unit attached to C-8;
HMBC correlations from H-11 to C-7/C-8/C‑12 (δC 31.2)/C-13 (δC
172.0), and from Me-14 to C-13, suggested that a methyl propio-
nate unit joined with C-7. By detailed analysis of its NMR data
and comparison of its physical and spectral data with those re-
ported in the literature [15], the structure of 3 was determined
to be as shown, and the compound was named oxalicumone C.
This is the first published assignment of the NMR data of 3.
Compounds 4–7 were the acetylated analogues of 1 that were
gained from 1 treated with acetic anhydride and 4-dimethylami-
nopyridine in dry pyridine at room temperature. Their structures
Compound 2 was treated separately with (S)-(+)- and (R)-
(−)-MTPA‑Cl in dry pyridine to yield the (R)- and (S)-MTPA ester
derivatives 2a and 2b, respectively. The shifted signals (H-6, H-7,
OH-11, H-12, Me-16, and Me-17) of the diastereomeric MTPA es-
ters (2a and 2b) were clearly different, and the observed chemical
shift differences (ΔδS‑R, see Supporting Information Fig. 34S)
clearly indicated the absolute configuration of C-13 in 2 to be R.
The 6R absolute configuration was proved by the CD data of 2 (see
Supporting Information Fig. 35S) that showed opposite Cotton ef-
fects at around 300 to 350 nm compared with that of oxalicu-
"
mone A (1) (l Fig. 4). In addition, we also obtained a known
chromone coniochaetone B [21]. The CD spectra of 2 and conio-
chaetone B (see Supporting Information Fig. 36S) had similar
positive Cotton effects at around 310 to 350 nm, which further
supported the R absolute configuration of C-6 in 2, because the
absolute configuration of the asymmetric carbon atom in conio-
chaetone B had been deduced to be R by application of Horeauʼs
method [21].
The absolute configuration of the C-11 tertiary alcohol in 2 was
assigned via the CD data of the in situ formed [Rh2(OCOCF3)4]
complex of 2b (MTPA ester of 2), with the inherent contribution
subtracted. According to the bulkiness rule [22,23], the Rh-com-
plex of 2b showed a positive E band at ca. 350 nm (see Supporting
Information Fig. 37S), revealing the 11S absolute configurations
in 2b and 2. In order to further verify the result, the absolute con-
figuration of the tert/sec 11,13-diol moiety in 2 was assigned us-
ing the in situ dimolybdenum CD method [24,25]. Upon addition
of dimolybdenum tetraacteate [Mo2(OAc)4] to 2 in DMSO solu-
tion, a metal complex was generated as an auxiliary chromo-
phore. The observed sign of the Cotton effect in the induced spec-
were determined based on analysis of their HRESIMS, 1H and 13
NMR data (l Tables 1 and 2), and comparison with those of 1.
C
"
Compounds 1–7 and 1a were tested for cytotoxicity against hu-
man melanoma A375, lung carcinoma A549, cervical carcinoma
HeLa, liver hepatocellular carcinoma HepG2, colonic adenocarci-
"
noma SW-620, and normal liver L-02 cell-lines (l Table 3). To-
wards A375 and SW-620 cell lines, 1a showed significant cyto-
toxicity with IC50s of 8.9 and 7.8 µM, 1 had moderate cytotoxicity
with IC50s of 11.7 and 22.6 µM, 2 and 5 showed mild cytotoxic-
ities, while the positive control cisplatin showed IC50 values of
7.3 and 30.0 µM, respectively. Compound 3 had no cytotoxicity
towards all test cells. The results indicated that the 2,3-dihydro-
thiophene unit was important for the cytotoxicities of these
chromones, and the substituent at OH-13, with large steric hin-
drance, might improve their cytotoxicities, whereas acetylation
at C-1, C-11, and/or C-13 reduced them.
Sun Y-L et al. Cytotoxic Dihydrothiophene-Condensed Chromones… Planta Med 2013; 79: 1474–1479

1478 Letters
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Materials and Methods
!
Strain and host gorgonian
The fungus Penicillium oxalicum SCSGAF 0023 was isolated from
the South China Sea gorgonian Muricella flexuosa. Detailed infor-
mation of fungal ITS gene sequencing and identification was giv-
en by Zhang et al. [10]. The gorgonian was collected from the
South China Sea, Sanya (18°11′ N, 109°25′ E), in August 2010,
and identified by Dr. Hui Huang and Xiu-bao Li (South China Sea
Institute of Oceanology, Chinese Academy of Sciences). The strain
of P. oxalicum (No. SCSGAF 0023) and a gorgonian voucher speci-
men (M. flexuosa) were deposited in South China Sea Institute of
Oceanology, Chinese Academy of Sciences.
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Isolates
Oxalicumone A (1): yellow oil; [α]2D0 + 31.43 (c 0.42, CHCl3), UV
(MeOH) λmax (log ε) 228 (3.88), 239 (3.90), 326 (3.18) nm; IR
(KBr): 3437, 1742, 1658, 1625, 1490, 1456, 1384, 1263, 1209,
1147, 1125, 1072, 1034, 996 cm−1
;
1H and
C NMR data, see
13
+
"
l Tables 1 and 2; (+)-ESIMS m/z 447 [M + Na] ; (+)-HRESIMS m/
z: [M + Na]+ 447.0693 (calcd. for C19H20O9SNa, 447.0726).
Oxalicumone B (2): yellow oil; [α]2D0 + 31.76 (c 0.17, CHCl3); UV
(MeOH) λmax (log ε) 226 (3.58), 241 (3.89), 326 (3.18) nm; IR
(KBr): 3437, 1746, 1658, 1491 cm−1
;
1H and C NMR data, see
13
+
"
l Tables 1 and 2; (+)-ESIMS m/z 447 [M + Na] ; (+)-HRESIMS m/
z: [M + Na]+ 447.0726 (calcd. for C19H20O9SNa, 447.0726).
Oxalicumone C (3): yellow oil; [α]2D0 + 11.25 (c 0.12, CHCl3), 1H
NMR (500 MHz, CDCl3) δ 11.95 (1H, s, 1-OH), 4.03 (1H, d,
J = 6.9 Hz, 15-OH), 6.67 (1H, s, H-2), 6.62 (1H, s, H-4), 5.23 (1H, d,
J = 6.9 Hz, H-15), 3.80 (3H, s, H-17), 3.73 (3H, s, H-14), 3.13 (2H,
td, J = 7.4, 3.6 Hz, H-11), 2.83 (2H, t, J = 7.4 Hz, H-12), 2.40 (3H, s,
H-18). 13C NMR (125 MHz, CDCl3) δ: 160.3 (s, C-1), 107.2 (d, C-
2), 147.9 (s, C-3), 112.4 (d, C-4), 156.0 (s, C-5), 167.0 (s, C-7),
118.2 (s,C‑8), 181.6 (s, C-9), 108.0 (s, C-10), 26.9 (t, C-11), 31.0 (t,
C-12), 172.0 (s, C-13), 52.2 (-OCH3, C-14), 66.3 (d, C-15), 173.1 (s,
C-16), 53.1 (-OCH3, C-17), 22.5 (CH3, C-18).
11 Steyn PS. Isolation, structure and absolute configuration of secalonic
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Supporting information
General experimental methods, details on the fermentation, ex-
traction, isolation, and MS, 1D-, and 2D- NMR spectra for com-
pounds 1–7, Δδ (δS – δR) values in ppm for MTPA esters of 2, CD
spectra of 2, coniochaetone B, Rh-complex of 2b and 2 in DMSO
containing Mo2(OAc)4 with the inherent CD spectrum subtracted
can be found as Supporting Information.
19 Rukachaisirikul V, Chantaruk S, Pongcharoen W, Isaka M, Lapanun S.
Chromone derivatives from the filamentous fungus Lachnum sp. BCC
2424. J Nat Prod 2006; 69: 980–982
Acknowledgements
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Structural revision and synthesis of altechromone A. J Nat Prod 2010;
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This work was financed by grants from NBRPC (973 Program,
2010CB833803), NMPWRPC (grant 201305017), NHTRDPC (863
Program, 2012AA092104), NSFC (40931160435, 40976090,
20872151), and CAS (KSCX2-EW-G-12B).
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Conflict of Interest
!
All the authors have no conflicts of interest.
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DOI http://dx.doi.org/10.1055/s-0033-1350805
Published online September 13, 2013
Planta Med 2013; 79: 1474–1479
© Georg Thieme Verlag KG Stuttgart · New York ·
ISSN 0032‑0943
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Correspondence
Prof. Dr. Shu-Hua Qi
Key Laboratory of Marine Bio-resources Sustainable Utilization
South China Sea Institute of Oceanology
The Chinese Academy of Sciences
164 West Xingang Road
Guangzhou 510301 Guangdong
China
received March 3, 2013
revised
July 7, 2013
accepted August 7, 2013
Phone: + 862089022112
Fax: + 862084458964
shuhuaqi@scsio.ac.cn
Sun Y-L et al. Cytotoxic Dihydrothiophene-Condensed Chromones… Planta Med 2013; 79: 1474–1479

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