Note pubs.acs.org/jnp
Violapyrones A−G, α‑Pyrone Derivatives from Streptomyces violascens Isolated from Hylobates hoolock Feces Jiaoyue Zhang,† Yi Jiang,‡ Yanru Cao,‡ Jiang Liu,§ Dan Zheng,† Xiu Chen,‡ Li Han,§ Chenglin Jiang,‡,§ and Xueshi Huang*,† †
Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, People’s Republic of China ‡ Yunnan Institute of Microbiology, Yunnan University, Kunming 650091, People’s Republic of China § Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, People’s Republic of China S Supporting Information *
ABSTRACT: Seven new 3,4,6-trisubstituted α-pyrone derivatives, violapyrones A−G (1−7), were isolated from Streptomyces violascens obtained from Hylobates hoolock feces. Their structures were elucidated on the basis of detailed spectroscopic analysis. The antimicrobial activities of 1−7 were evaluated against Gram-positive and Gram-negative bacteria and against fungi. Compounds 1−3 showed moderate antibacterial activities against Bacillus subtilis and Staphylococcus aureus with MIC values of 4−32 μg/mL.
A
UV maximum peak at 290.3 nm together with NMR data indicated it contained a typical α-pyrone chromophore.10,11 The α-pyrone ring was elucidated as 3-methyl-4-hydroxypyran2-one with a substituted moiety at C-6 by analysis of the 1H NMR signals at δH 5.96 (1H, s) and 1.72 (3H, s) and 13C NMR signals at δC 165.58, 165.51, 162.9, 99.8, 96.9, and 8.8, with the aid of HMBC correlations between δH 5.96/δC 165.51, 162.9 and δH 1.72/δC 165.58. From the 1H NMR spectrum, three methylenes, one methine, and two methyls with the same chemical shifts were found at δH 2.37 (2H, t, J = 7.3), 1.51 (2H, m), 1.50 (1H, m), 1.15 (2H, q, J = 6.9), and 0.84 (6H, d, J = 6.6). The corresponding carbons at δC 38.0 (CH2), 33.2 (CH2), 27.7 (CH2), 24.6 (CH), and 22.8 (CH3) were present in the 13 C NMR spectrum. A 4-methylpentyl was clearly inferred on the basis of COSY correlations between δH 2.37/1.51/1.15/ 1.50/0.84. The linkage of the alkyl chain to C-6 of the α-pyrone ring was further confirmed by HMBC correlations between δH 2.37/δC 162.9, δH 1.51/δC 162.9, and δH 5.96/δC 33.2. Thus, the structure of 1 was determined as 4-hydroxy-3-methyl-6-(4methylpentyl)-2H-pyran-2-one, named violapyrone A. Structure elucidation of violapyrones B−G (2−7) was straightforward because of their close structural relationships to violapyrone A (1). Violapyrone B (2) showed the molecular formula C13H20O3, as determined by HRESIMS, having one
nimal feces have been considered a diverse, abundant, and important microbial resource for discovering novel bioactive natural products.1−5 Several new compounds had been found from actinobacteria associated with animal feces.5−8 The coauthors at Yunnan University have studied the diversity of cultivable actinobacteria from five animal feces (Hylobates hoolock, Rhinopithecus bieti, Panthera tigris altaica, Ailurus f ulgens, and Viverra zibetha).9 A total of 119 strains belonging to 20 genera of actinobacteria were isolated and identified. As part of our investigation on new bioactive compounds from fecal microorganisms, the secondary metabolites of Streptomyces violascens (YIM 100525) obtained from Hylobates hoolock feces, which showed antibacterial activity and diverse chemical constituents by physicochemical analysis, were investigated. Seven 3,4,6-trisubstituted α-pyrone derivatives, violapyrones A−G (1−7), were isolated from the fermentation broth of YIM 100525. The cytotoxicities against five human cancer cell lines and the antimicrobial activities against Gram-positive and Gram-negative bacteria and against fungi were evaluated. None of these compounds showed significant cytotoxic activities against five human carcinoma cell lines (IC50 > 200 μM). However, compounds 1−3 showed modest antibacterial activities against Bacillus subtilis and Staphylococcus aureus with MIC values of 4−32 μg/mL. Compound 1 was obtained as a white, amorphous powder, and the molecular formula was determined to be C12H18O3 by HREIMS. Its IR absorption at 3419, 1638, and 1577 cm−1 and © 2013 American Chemical Society and American Society of Pharmacognosy
Received: April 25, 2013 Published: November 1, 2013 2126
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more CH2 unit than that of 1. Comparison of its 1H and 13C NMR data with those of 1 revealed the existence of the same 3methyl-4-hydroxy-α-pyrone framework as that in 1. The side chain at C-6 was assigned as 5-methylhexyl, as deduced from 1 H and 13C NMR data. Unambiguous and complete assignments of the atoms in the structure of 2 were achieved with HMQC, HMBC, and COSY experiments. The molecular formula of 3 was obtained as C14H22O3 by HREIMS, containing one more CH2 unit than that of 2. The 1 H and 13C NMR data of 3 were characteristic of a 3-methyl-4hydroxypyran-2-one fragment and an alkyl residue at the C-6 position. Five methylenes, one methine, one doublet methyl, and one triplet methyl were observed in the 1H NMR spectrum, suggesting the alkyl side chain to be 5-methylheptyl, which was confirmed by COSY experiment. Violapyrone D (4) has the molecular formular C14H20O4, as determined by HRESIMS, with five degrees of unsaturation. 1H and 13C NMR data showed 4 had the same basic structure as that of 1−3. Four methylenes at δH 2.45 (2H, t, J = 7.5), 1.64 (2H, m), 1.30 (2H, m), 1.69 (1H, m), and 1.36 (1H, m), one methine at δH 2.52 (1H, m), one singlet methyl at δH 2.15 (3H, s), and one doublet methyl at δH 1.09 (3H, d, J = 7.0) were observed in the 1H NMR spectra. The corresponding carbon signals at δC 47.2 (CH), 33.4 (CH2), 32.5 (CH2), 28.4 (CH3), 26.9 (CH2), 26.6 (CH2), and 16.7 (CH3), as well as one more ketone carbonyl at δC 214.1, were present in the 13C NMR spectra. These NMR data suggested a 5-methyl-6-oxoheptyl existed in 4. HMBC correlations from δH 2.52 (H-11), 1.09 (Me-11), and 2.15 (Me-12) to δC 214.1 (C-12) confirmed the assignments of the side chain (Figure 1).
Violapyrone E (5) has the molecular formula C14H22O4, as determined by HREIMS. Comparison of its 1H and 13C NMR data with those of 4 showed one more oxygenated methine signal at δ 69.4/3.42 (1H, quint, J = 6.0), and the signal for the carbonyl in 4 was absent. This information led to the assignment of the structure of 5 as 4-hydroxy-3methyl-6-(5methyl-6-hydroxyheptyl)-2H-pyran-2-one, which was determined by COSY, HSQC, and HMBC experiments. The absolute configuration of C-12 was determined by the classical Mosher’s method. Treatment of 5 with (S)-MTPACl or (R)MTPACl afforded the R and S Mosher’s esters 5a and 5b. The signal of the methyl at C-12 for 5a was observed at a weaker field (δ = 1.18) compared to the signal for 5b (δ = 1.14), which indicated the absolute configuration of C-12 to be S. The molecular formula of violapyrone F (6) was assigned to be C13H20O4 on the basis of HREIMS. Its spectroscopic characteristics were close to those of violapyrone B (2), except that an oxygenated quaternary carbon was observed in the downfield region instead of the methine in 6. It accounted for a hydroxyl unit difference between the molecular formulas of 2 and 6. In the HMBC spectrum, the correlations from δH 1.31 (H-10) and 1.04 (Me-11) to δC 69.1 (C-11) suggested the hydroxyl was located at C-11. Therefore, the structure of violapyrone F was unambiguously elucidated as 6. The 1H and 13C NMR data of 7 were very similar to those of 6, except for an additional methoxy signal (δH 3.88/δC 56.1). HMBC correlations from δH 3.88 to δC 165.8 (C-4), 100.9 (C3), and 94.3 (C-5) established that the methoxy group was located at C-3. 4-Hydroxy-6-alkyl-α-pyrones have been reported mainly from fungi, but they are also found in marine animals, plants, and bacteria.12,13 There are few reports of the isolation of these compounds from streptomycetes.14 Compounds 1−7 were evaluated for their cytotoxic and antimicrobial activities, which are commonly associated with α-pyrones.15−19 Compounds 1− 7 were inactive against the five cell lines used to evaluate cytotoxicity (IC50 > 200 μM). Compounds 1−3 showed moderate antibacterial activities against Bacillus subtilis and
Figure 1. Key HMBC and COSY correlations of 4 in CDCl3.
Table 1. 1H and 13C NMR Data for Compounds 1−4 1a,c position 2 3 4 5 6 7 8 9 10
δC, type 165.58, C 96.9, C 165.51, C 99.8, CH 162.9, C 33.2, CH2 27.7, CH2 38.0, CH2 24.6, CH
2a,d δH (J in Hz)
5.96, s 2.37, 1.51, 1.15, 1.50,
t (7.3) m q (6.9) m
11 12 3-Me 4-OH 10-Me 11-Me 12-Me a
δC, type 165.2, 96.6, 164.9, 99.2, 162.6, 32.6, 26.6, 26.1, 38.1,
C C C CH C CH2 CH2 CH2 CH2
27.4, CH
8.8, CH3 22.8, CH3
1.72, s
8.4, CH3
3a,c δH (J in Hz)
5.98, s 2.41, 1.50, 1.27, 1.16,
t (7.3) m m m
1.49, m
1.74, s 11.13, brs
δC, type 165.6, 96.9, 165.4, 99.7, 163.0, 33.0, 27.1, 26.2, 36.1,
C C C CH C CH2 CH2 CH2 CH2
34.1, CH 29.3, CH2 8.8, CH3
4b,c δH (J inHz)
5.97, s 2.41, t (7.3) 1.51, m 1.26, m 1.28, m 1.08, m 1.27, m 1.28, m 1.09, m 1.74, s 11.10, brs
δC, type 168.0, 98.8, 166.4, 100.8, 162.9, 33.4, 26.9, 26.6, 32.5,
C C C CH C CH2 CH2 CH2 CH2
47.2, CH 214.1, C 8.4, CH3
δH (J in Hz)
6.13, s 2.45, 1.64, 1.30, 1.69, 1.36, 2.52,
t (7.5) m m m m m
1.96, s
0.84, d (6.6) 22.5, CH3
0.85, d (6.6)
19.5, CH3 11.7, CH3
0.82, d (6.3) 0.84, t (6.6)
16.7, CH3 28.4, CH3
1.09, d (7.0) 2.15, s
In DMSO-d6. bIn CDCl3. cIn 600 MHz. dIn 400 MHz. 2127
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Table 2. 1H and 13C NMR Data for Compounds 5−7 5a,c δC, type
position 2 3 4 5 6 7 8 9
a
165.3, 96.5, 165.3, 99.4, 162.6, 32.6, 26.8, 26.1,
6a,c δH (J in Hz)
C C C CH C CH2 CH2 CH2
δC, type 167.6, 96.0, 165.9, 100.8, 162.4, 33.2, 27.6, 23.7,
5.96, s
10
32.0, CH2
11 12 3-Me 4-OMe 11-OH 11-Me 12-Me
39.5, CH 69.4, CH 8.5, CH3
2.41, 1.50, 1.33, 1.19, 1.41, 1.00, 1.34, 3.42, 1.74,
t (7.0) m m m m m m quint (6.0) s
14.6, CH3 19.4, CH3
0.76, d (6.7) 0.97, d (6.4)
C C C CH C CH2 CH2 CH2
43.7, CH2
7b,c δH (J in Hz)
5.94, s 2.36, t (7.3) 1.48, m 1.30, m 1.31, m
69.1, C
δC, type 165.8, 100.9, 165.8, 94.3, 164.1, 34.1, 27.5, 23.6,
C C C CH C CH2 CH2 CH2
43.3, CH2
δH (J in Hz)
6.01, s 2.52, t (7.5) 1.50, m 1.42, m 1.48, m
70.7, C
9.0, CH3
1.71, s
8.4, CH3 56.1, CH3
29.7, CH3
1.04, s
29.3, CH3
1.91, 3.88, 5.91, 1.22,
s s brs s
In DMSO-d6. bIn CDCl3. cIn 600 MHz.
Staphylococcus aureus, with MIC values of 4−32 μg/mL. Compounds 4−7 showed weak activity or were inactive against B. subtilis and S. aureus, and none of these compounds were effective against other tested microorganisms (Table 3). Our
spectra were performed with a Waters 2695 separation module and a Waters 2996 photodiode array detector. Solid-phase extraction was done on Amberlite XAD 16 polymeric resin (Rohm and Haas Shanghai Chemical Industry Co., Ltd., Shanghai, China). Silica gel (100−200 and 200−300 mesh, Qingdao Marine Chemical Ltd., Qingdao, China), Sephadex LH-20 (GE Healthcare Bioscienses AB, Uppsala, Sweden), and YMC*GEL ODS-A (S-50 μm, 12 nm) (YMC Co., Ltd., Kyoto, Japan) were used for column chromatography. The MTT assay was recorded on a microplate reader (KHB ST-360, SH Kehua Laboratory System Co., Ltd., Shanghai, China). Streptomycetes Isolate. The producing strain was isolated from fresh fecal samples excreted by healthy adult Hylobates hoolock (Hoolock gibbon) living in Yunnan Wild Animal Park, Kunming, Yunnan Province, P. R. China, in October 2009. The strain was identified as Streptomyces violascens by one of the authors (Y.J.) based on morphological characteristics and 16S rRNA gene sequences. The Blast result showed that the sequence was most similar (99.31%) to the sequence of S. violascens (strain: NBRC 12920, GenBank accession no. AB184246). The strain (No.YIM 100525) was deposited in Yunnan Institute of Microbiology, Yunnan University, China. Fermentation, Extraction, and Isolation. A slant culture of the strain was inoculated into 500 mL Erlenmeyer flasks containing 100 mL of seed medium composed of yeast extract 4 g L−1, glucose 4 g L−1, malt extract 5 g L−1, multiple vitamins solution 1.0 mL L−1, and trace element solution 1.0 mL L−1; the pH was 7.2 with no adjustment; and the flasks were incubated for 2 days at 28 °C on a rotary shaker at 180 rpm. A 10 mL amount of this seed culture was used to inoculate 500 mL Erlenmeyer flasks containing 100 mL of fermentation medium containing soybean meal 10 g L−1, peptone 2 g L−1, glucose 20 g L−1, soluble starch 5 g L−1, yeast extract 2 g L−1, NaCl 4 g L−1, K2HPO4 0.5 g L−1, MgSO4·7H2O 0.5 g L−1, and CaCO3 2 g L−1, with a pH of 7.8 with no adjustment, and incubated for 7 days at 28 °C on a rotary shaker at 180 rpm. The completed fermentation broth (70 L) was separated into filtrate and mycelium by centrifugation. The supernatant was absorbed onto the Amberlite XAD-16 polymeric resin. Salt and high molecular weight materials were washed out with water; other organic materials were eluted with EtOH to give 30.3 g of crude extract by rotary evaporation under reduced pressure. The total extract was subjected to open silica gel (100−200 mesh) column chromatography (CC) with a CH2Cl2−MeOH solvent system (from 50:1 to 15:1 and finally 1:1) to yield 11 fractions. Fraction 2 (1.24 g) was subjected to gel chromatography on Sephadex LH-20 (MeOH) to produce nine
Table 3. Antimicrobial Activities of 1−7 (MICa μg/mL) S. aureas B. subtilius E. coli P. aeruginosa C. albicans A. niger
1
2
3
4
5
8 32
4 4
16 16
128
128 128
6
7
control
128
0.5b 0.12b 0.12b 0.25b 0.5c 1.0c
a
The data for the minimal inhibitory concentration (MIC) represent the mean of three independent experiments. bCiprofloxacin. c Amphotericin B.
result suggested that the unsaturation of the alkyl side chain of α-pyrones affected the cytotoxicity since it lost cytotoxic activity after the unsaturated alkyl (e.g., nigerapyrones B, D, and E and siphonarienolones) was replaced by the saturated alkyl group.15,16 Moreover, α-pyrones were less active as antibacterial agents if the alkyl chain was oxygenated. In addition, these experimental results were consistent with results reported in the literature in which α-pyrones exhibited moderate activity against Gram-positive bacteria, but they were inactive against Gram-negative bacteria and fungi.18,19
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EXPERIMENTAL SECTION
General Experimental Procedures. Optical rotations were determined using an SGW-1 automatic polarimeter (Shanghai Precision & Scientific Instrument Co., Ltd., Shanghai, China). ESIMS were recorded by a Thermo Finnigan LCQ mass spectrometer (Thermo Electron, San Jose, CA, USA). HRESIMS were measured with a Waters LCT Premier XE TOF mass spectrometer (Waters, Milford, MA, USA). HREIMS was determined on an Autospec Premier P776 mass spectrometer (Waters). NMR spectra were recorded on a Bruker Advance III-600 MHz and a Bruker AM-400 MHz spectrometer (Bruker, Rheinstetten, Germany). Ultraviolet 2128
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and two fungi (Candida albicans ATCC 10231, Aspergillus niger ATCC 1015) were carried out using the micro broth dilution method.21 Ciprofloxacin and amphotericin B were used as positive controls against bacteria and fungi, respectively.
subfractions (Fr.2.1−Fr.2.9). Fr.2.5 (663 mg) was further separated by ODS CC, eluting with water−methanol (20:80), to yield six subfractions (Fr.2.5.1−Fr.2.5.6). Fr.2.5.3 (133 mg) was purified by silica gel (200−300 mesh) CC (P. ether−EtOAc, 5:1) to give compound 1 (75.3 mg). Fr.2.5.4 (370 mg) and Fr.2.5.5 (28.0 mg) were purified by silica gel (200−300 mesh) CC (P. ether−EtOAc, 6:1) to give compounds 2 (246 mg) and 3 (19.2 mg), respectively. Fraction 3 (852 mg) was also separated by gel chromatography on Sephadex LH-20 (MeOH) into eight subfractions (Fr.3.1−Fr.3.8). Fr.3.3 (397 mg) was purified by silica gel (200−300 mesh) CC (P. ether−EtOAc, 2:1) to yield compounds 4 (78.0 mg) and 7 (49.5 mg). Compound 5 (63.0 mg) was obtained from Fr.5 (484 mg), using ODS CC, eluting with water−methanol (40:60) and purifying by silica gel (300−400 mesh) CC (P. ether−EtOAc, 1:1). Fraction 7 (784 mg) was subjected to Sephadex LH-20 CC (MeOH), then further separated by silica gel (200−300 mesh) CC (P. ether−EtOAc, 2:3) to yield compound 6 (342 mg). Violapyrone A (1): white, amorphous powder; UV (MeOH) λmax 290.3 nm; IR (KBr) νmax 3419, 2956, 2931, 1638, 1577, 1409, 1249, 1175, 1124 cm−1; 1H NMR and 13C NMR see Table 1; ESIMS m/z 209 [M − H]−, 245 [M + Cl]−; HREIMS m/z 210.1261 [M]+ (calcd for C12H18O3, 210.1256). Violapyrone B (2): white, amorphous powder; UV (MeOH) λmax 290.3 nm; IR (KBr) νmax 3384, 2958, 2931, 1691, 1656, 1566, 1466, 1382, 1247, 1170 cm−1; 1H NMR and 13C NMR see Table 1; ESIMS m/z 223 [M − H]−; HRESIMS m/z 225.1488 [M + H]+ (calcd for C13H21O3, 225.1491). Violapyrone C (3): white, amorphous powder; [α]20 D 0 (c 0.66, MeOH); UV (MeOH) λmax 290.3 nm; IR (KBr) νmax 3146, 2956, 2940, 1664, 1649, 1596, 1446, 1240, 1172, 1118 cm−1; 1H NMR and 13 C NMR see Table 1; HREIMS m/z 238.1571 [M]+ (calcd for C14H22O3, 238.1569). Violapyrone D (4): colorless oil; [α]20 D 0 (c 0.58, MeOH); UV (MeOH) λmax 290.3 nm; IR (KBr) νmax 3423, 2968, 2930, 1708, 1662, 1631, 1584, 1408, 1258, 1176, 1129 cm−1; 1H NMR and 13C NMR see Table 1; HRESIMS m/z 253.1438 [M + H]+ (calcd for C14H21O4, 253.1440). Violapyrone E (5): colorless oil; [α]20 D +17.2 (c 0.65, MeOH); UV (MeOH) λmax 290.3 nm. IR (KBr) νmax 3440, 2963, 2928, 1685, 1647, 1589, 1412, 1257, 1125 cm−1; 1H NMR and 13C NMR see Table 2; HREIMS m/z 254.1517 [M]+ (calcd for C14H22O4, 254.1518). (R)-MTPA ester 5a: 5 (2 mg) was acylated with (S)-MTPACl by Mosher’s method5 and purified on silica gel (200−300 mesh) CC (CH2Cl2−MeOH, 80:1) to obtain (R)-MTPA ester 5a, 1.2 mg: 1H NMR (300 MHz, DMSO-d6) δ 11.11 (1H, s), 7.48 (5H, m), 5.96 (1H, s), 4.98 (1H, quint), 3.49 (3H, s), 1.74 (3H, s), 1.18 (3H, d, 6.6), 0.85 (3H, overlapped); ESIMS m/z 471 [M + H]+, 493 [M + Na]+. (S)-MTPA ester 5b: In an entirely analogous way, the (S)-MTPA ester (5b, 0.5 mg) was prepared using (R)-MTPACl: 1H NMR (300 MHz, DMSO-d6) δ 11.14 (1H, s), 7.49 (5H, m), 5.99 (1H, s), 5.01 (1H, quint), 3.46 (3H, s), 1.74 (3H, s), 1.14 (3H, d, 6.6), 0.85 (3H, overlapped); ESIMS m/z 471 [M + H]+, 493 [M + Na]+. Violapyrone F (6): colorless oil; UV (MeOH) λmax 204.2, 290.3 nm; IR (KBr) νmax 3417, 2966, 2936, 1676 (br), 1587, 1413, 1247, 1172, 1125 cm−1; 1H NMR and 13C NMR see Table 2; HREIMS m/z 240.1359 [M]+ (calcd for C13H20O4, 240.1362). Violapyrone G (7): colorless oil; UV (MeOH) λmax 299.8 nm; IR (KBr) νmax 3400, 2960, 2928, 1638, 1578, 1406, 1239, 1174, 1125 cm−1; 1H NMR and 13C NMR see Table 2; HRESIMS m/z 255.1586 [M + H]+ (calcd for C14H23O4, 255.1596). Cytotoxicity Assay. Five human cancer cell lines, BGC-823, HepG2, H460, HeLa, and HCT-116, were used to evaluate cytotoxic effects of 1−7 employing an MTT method.20 IC50 was defined as a 50% reduction of absorbance in the control assay. Adriamycin as a positive control showed IC50 values of 1.48, 0.50, 0.98, 0.97, and 1.38 μM against BGC-823, HepG2, H460, HeLa, and HCT-116 cell lines, respectively. Antimicrobial Assay. Antimicrobial assays against four bacteria (Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Paeudomonas aeruginosa ATCC 27853)
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ASSOCIATED CONTENT
* Supporting Information S
1D and 2D NMR spectra for compounds 1−7. This material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*Tel: 0086-24-23251769. Fax: 0086-24-23251769. E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We are grateful to Mr. Y. Li and Ms. S. Qiu (Yunnan Wild Animal Park) for helping to collect the animal feces. This work was funded by National Natural Science Foundation of China (Grant Nos. 31270001 and 81072553).
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REFERENCES
(1) Ley, R. E.; Hamady, M.; Lozupone, C.; Turnbaugh, P. J.; Ramey, R. R.; Bircher, J. S.; Schlegel, M. L.; Tucker, T. A.; Schrenzel, M. D.; Knight, R.; Gordon, J. I. Science 2008, 320, 1647−1651. (2) Cao, Y. R.; Jiang, Y.; Jin, R. X.; Han, L.; He, W. X.; Li, Y. L.; Huang, X. S.; Xue, Q. H. Int. J. Syst. Evol. Microbiol. 2012, 62, 2710− 2716. (3) Yildirim, S.; Yeoman, C. J.; Sipos, M.; Torralba, M.; Wilson, B. A.; Goldberg, T. L.; Stumpf, R. M.; Leigh, S. R.; White, B. A.; Nelson, K. E. PLoS ONE 2010, 5, 1−11. (4) Tan, H.; Deng, Z.; Cao, L. Lett. Appl. Microbiol. 2009, 49, 248− 253. (5) Zheng, D.; Han, L.; Jiang, Y.; Cao, Y. R.; Liu, J.; Chen, X.; Li, Y. Q.; Huang, X. S. Magn. Reson. Chem. 2013, 51, 188−191. (6) Yang, S. X.; Gao, J. M.; Zhang, A. L.; Jiang, Y.; Cao, Y. R.; Laatsch, H. Bioorg. Med. Chem. 2011, 21, 3905−3908. (7) Matsui, T.; Tanaka, J.; Namihira, T.; Shinzato, N. J. Basic Microbiol. 2012, 52, 731−735. (8) Bérdy, J. J. Antibiot. 2012, 65, 385−395. (9) Jiang, Y.; Cao, Y. R.; Han, L.; Jin, R. X.; Zheng, D.; He, W. X.; Li, Y. L.; Huang, X. S. Acta Microbiol. Sin. 2012, 52, 1282−1289. (10) Cutignano, A.; Fontana, A.; Renzulli, L.; Cimino, G. J. Nat. Prod. 2003, 66, 1399−1401. (11) Fu, P.; Liu, P. P.; Qu, H. J.; Wang, Y.; Chen, D. F.; Wang, H.; Li, J.; Zhu, W. M. J. Nat. Prod. 2011, 74, 2219−2223. (12) Dictionary of Natural Products on DVD, version 21.2; Chapman & Hall/CRC: London, 2013. (13) Li, C.; Nitka, M. V.; Gloer, J. B. J. Nat. Prod. 2003, 66, 1302− 1306. (14) Ohno, H.; Saheki, T.; Awaya, J.; Nakagawa, A.; Omura, S. J. Antibiot. 1978, 31, 1116−1123. (15) Paul, M. C.; Zubía, E.; Ortega, M. J.; Salvá, J. Tetrahedron 1997, 53, 2303−2308. (16) Liu, D.; Li, X. M.; Meng, L.; Li, C. S.; Gao, S. S.; Shang, Z.; Proksch, P.; Huang, C. G.; Wang, B. G. J. Nat. Prod. 2011, 74, 1787− 1791. (17) Rukachaisirikul, V.; Rodglin, A.; Phongpaichit, S.; Buatong. J. Phytochem. Lett. 2012, 5, 13−17. (18) Irschik, H.; Jansen, R.; Höfle, G.; Gerth, K.; Reichenbach, H. J. Antibiot. 1985, 38, 145−152. (19) Singh, M. P.; Kong, F.; Janso, J. E.; Arias, D. A.; Suarez, P. A.; Berana, V. S.; Petersen, P. J.; Weiss, W. J.; Carter, G.; Greenstein, M. J. Antibiot. 2003, 56, 1033−1044. 2129
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Journal of Natural Products
Note
(20) Zheng, D.; Han, L.; Li, Y. Q.; Li, J.; Rong, H.; Leng, Q.; Jiang, Y.; Zhao, L. X.; Huang, X. S. Molecules 2012, 17, 836−842. (21) Zhao, J. L.; Mou, Y.; Shan, T. J.; Li, Y.; Zhou, L. G.; Wang, M. G.; Wang, J. G. Molecules 2010, 15, 7961−7970.
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dx.doi.org/10.1021/np4003417 | J. Nat. Prod. 2013, 76, 2126−2130
