Article pubs.acs.org/jnp
Aliphatic Phenolic Ethers from Trichobotrys ef f usa Jih-Jung Chen,† Shih-Wei Wang,‡ Hui-Yun Hsiao,§ Ming-Shian Lee,⊥ Yu-Min Ju,∥ Yueh-Hsiung Kuo,#,▽ and Tzong-Huei Lee*,§ †
Department of Pharmacy, Tajen University, Pingtung, Taiwan 907 Department of Medicine, Mackay Medical University, Taipei, Taiwan 252 § Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan 110 ⊥ College of Pharmacy, Taipei Medical University, Taipei, Taiwan 110 ∥ Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan 115, # Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan 404 ▽ Department of Biotechnology, Asia University, Taichung, Taiwan 413 ‡
S Supporting Information *
ABSTRACT: Four novel aliphatic phenolic ethers, namely, trichoethers A−D (1−4), possessing a unique C11−O−C10 skeleton, together with coriloxin, zythiostromic acid A, radicicol, and 3,5-dihydroxytoluene were isolated from the ethyl acetate extracts of the fermented broths of Trichobotrys eff usa YMJ1179. The structures of all the compounds were determined based on spectroscopic data analysis. The configurations of 1−4 were established by J values and NOESY and compared with published data. Compounds 1−4 and radicicol exhibited growthinhibitory activities against the A549 non-small-cell lung cancer cell line with GI50 values of 25.61, 19.32, 16.19, 24.31, and 1.43 μM, respectively, in comparison with 5-fluorouracil (GI50 = 4.55 μM).
A
lthough the secondary metabolites of microorganisms have been investigated extensively worldwide for the development of agriculturally and medicinally useful agents over the past decades, it was estimated that less than 5% of all the fungal species in nature have been identified thus far.1 This means fungi are still one of the most important options for looking for novel chemical entities and bioactive compounds. Located in both tropical and subtropical regions, Taiwan is abundant in highly diversified fungal species, and over 6600 species have been reported.2 In an attempt to make good use of the local natural resources, fungal strains were screened by biological platforms to select those strains with significant bioactivities for further investigations. Trichobotrys ef f usa (Berkeley & Broome) Petch [synonyms Sporodum ef f usum Berk. & Broome and Dematium ef f usum (Berk. & Broome) Sacc.] was classified as a deuteromycota due to its lack of sexual reproduction and was described for the first time in 1886. 3 Our preliminary pharmacological evaluation demonstrated that the ethyl acetate extracts of the fermented broths of T. ef f usa YMJ1179 displayed significant growth-inhibitory activity against the A549 lung cancer cell line with a GI50 value of 17.0 μg/mL. 4 Furthermore, in a survey of the SciFinder database (American Chemical Society), no literature regarding the secondary metabolites of this fungus was found. Subsequently the bioactive constituents in the fermented broth of this fungus were studied, © 2014 American Chemical Society and American Society of Pharmacognosy
Figure 1. Chemical structures of 1−4 identified in this report.
which led to the isolation and characterization of four novel chemical entities, 1−4 (Figure 1), together with four known compounds. This paper herein describes the separation and identification of these compounds together with their bioactivities. Received: September 24, 2013 Published: May 5, 2014 1097
dx.doi.org/10.1021/np400776y | J. Nat. Prod. 2014, 77, 1097−1101
Journal of Natural Products
Article
Table 1. 1H and 13C NMR Spectroscopic Data for Compounds 1−4 [δ in ppm, mult. (J in Hz)] 1
a
no.
13 a
1 2 3 4 5 6 7 8 9 10
14.0 q 24.7 t 35.1 t 142.0 s 121.4 d 129.1 d 114.4 d 156.5 s 120.7 s 64.5 t
11 12 13 14 15 16 17 18 19
88.3 d 133.7 s 135.7 d 124.1 d 136.7 d 131.5 d 132.3 d 18.4 q 56.6 t
20 21 22 23
69.1 d 19.1 q
C
2 Hb
1
0.89 t (7.5) 1.48 sex (7.5) 2.49 t (7.5) 6.68 d (7.8) 7.08 t (7.8) 6.71 d (7.8)
4.46 d (11.7) 4.68 d (11.7) 3.73 d (5.9) 6.17 d (11.3) 6.47 dd (14.6, 11.3) 6.29 dd (14.6, 10.8) 6.14 dd (14.3, 10.8) 5.80 dq (14.3, 7.0) 1.79 d (7.0) 4.24 d (12.0) 4.33 d (12.0) 4.01 quin (5.9) 1.15 d (5.9)
13 a
13.9 q 24.9 t 35.4 t 141.8 s 121.1 d 129.3 d 114.6 d 157.3 s 120.1 s 65.9 t
3 Hb
13 a
1
C
0.88 t (7.5) 1.45 sex (7.5) 2.51 t (7.5)
14.0 q 24.6 t 35.4 t 141.2 s 121.5 d 129.0 d 114.6 d 156.7 s 120.1 s 65.1 t
6.65 d (7.5) 7.10 t (7.7) 6.80 d (7.7)
4.56 d (10.7) 4.67 d (10.7) 5.22 s
77.8 d 132.9 s 154.6 d 124.5 d 147.2 d 131.7 d 139.6 d 18.8 q 191.8 d
7.05 d (11.8) 6.54 dd (14.6, 11.8) 6.63 dd (14.6, 10.8) 6.22 dd (14.7, 10.8) 6.07 dq (14.7, 7.0) 1.84 d (7.0) 9.46 s
206.4 s 26.0 q
2.06 s
4 Hb
1
C
0.92 t (7.5) 1.51 sex (7.5) 2.52 t (7.5) 6.69 d (7.8) 7.09 t (7.8) 6.72 d (7.8)
4.72 d (12.0) 4.83 d (12.0) 4.13 s
85.0 d 135.7 s 132.1 d 125.3 d 137.3 d 131.5 d 132.7 d 18.4 q 103.1 d
6.35 d (9.6) 6.25 dd (14.6, 9.6) 6.24 dd (14.6, 9.0) 6.12 dd (14.5, 9.0) 5.80 dq (14.5, 7.0) 1.78 d (7.0) 5.53 s
108.8 s 16.9 q 48.9 q 55.8 q
1.46 s 3.30 s 3.51 s
13 a
1
C
14.0 q 24.6 t 35.4 t 141.2 s 121.5 d 129.0 d 114.6 d 156.8 s 120.2 s 64.7 t 84.5 d 136.9 s 127.1 d 125.2 d 135.5 d 131.4 d 132.0 d 18.4 q 67.2 t 108.2 s 15.9 q 48.4 q
Hb
0.92 t (7.5) 1.51 sex (7.5) 2.53 t (7.5) 6.68 d (7.9) 7.09 t (7.9) 6.72 d (7.9)
4.70 d (12.1) 4.85 d (12.1) 3.97 s 6.22 d (11.3) 5.92 dd (14.3, 11.3) 6.20 dd (14.3, 10.9) 6.09 dd (14.5, 10.9) 5.78 dd (14.5, 7.0) 1.78 d (7.0) 4.41 d (13.5) 4.59 d (13.5) 1.47 s 3.23 s
Multiplicities were obtained from phase-sensitive HSQC experiments. bMeasured in CDCl3, 500 MHz.
■
RESULTS AND DISCUSSION From the EtOAc extracts of the fermented broths of T. ef f usa YMJ1179, eight compounds including four novel aliphatic phenolic ethers (1−4) and four known compounds, coriloxin, zythiostromic acid A, radicicol, and 3,5-dihydroxytoluene, were isolated by a series of separations on Sephadex LH-20, Diaion HP-20, and reversed-phase HPLC. Coriloxin was obtained as a colorless crystal whose 1H NMR, 13C NMR, IR, optical rotation, and MS were consistent with those of the known compound isolated previously from a xylariaceous endophytic fungus, #YUA-026.5 Spectroscopic data of zythiostromic acid A coincided with those reported in the literature.6 The data for radicicol, a chloride-containing macrolide, were identified to be the same as previously reported data.7 The spectral data of 3,5dihydroxytoluene were in good agreement with the published data.8 Compound 1 was obtained as a colorless oil, and its IR absorptions at 3373 and 1587 and 1463 cm−1 indicated the presence of a hydroxyl group and an aromatic functionality, respectively. HRESIMS of 1 showed a prominent pseudomolecular ion [M − H]− at m/z 345.2076 (calcd for C21H29O4, 345.2066), and this coupled with its 13C NMR (Table 1) established its molecular formula as C21H30O4. The 13C NMR accompanied by a phase-sensitive HSQC experiment of 1 revealed 21 resonances including 12 olefinic signals at δC 156.5 (s), 142.0 (s), 136.7 (d), 135.7 (d), 133.7 (s), 132.3 (d), 131.5 (d), 129.1 (d), 124.1 (d), 121.4 (d), 120.7 (s), and 114.4 (d), two carbinoyl carbons at δC 88.3 (d) and 69.1 (d), two oxymethylene carbons at δC 64.5 (t) and 56.6 (t), two methylene carbons at δC 35.1 (t) and 24.7 (t), and three terminal methyl carbons at δC 19.1 (q), 18.4 (q), and 14.0 (q) (Table 1). The 1H NMR in combination with the COSY
Figure 2. Key COSY, HMBC, and NOESY of 1.
(Figure 2) of 1 showed resonances constructing four structural pieces at δH 0.89 (3H, t, J = 7.5 Hz, H3-1)/1.48 (2H, sex, J = 7.5 Hz, H2-2)/2.49 (2H, t, J = 7.5 Hz, H2-3), 1.79 (3H, d, J = 7.0 Hz, H3-18)/5.80 (1H, dq, J = 14.3, 7.0 Hz, H-17)/6.14 (1H, dd, J = 14.3, 10.8 Hz, H-16)/6.29 (1H, dd, J = 14.6, 10.8 Hz, H-15)/6.47 (1H, dd, J = 14.6, 11.3 Hz, H-14)/6.17 (1H, d, J = 11.3 Hz, H-13), 6.68 (1H, d, J = 7.8 Hz, H-5)/7.08 (1H, t, J = 7.8 Hz, H-6)/6.71 (1H, d, J = 7.8 Hz, H-7), and 3.73 (1H, d, J = 5.9 Hz, H-11)/4.01 (1H, quin, J = 5.9 Hz, H-20)/1.15 (3H, d, J = 5.9 Hz, H3-21) along with two isolated oxymethylenes at δH 4.68, 4.46 (each 1H, d, J = 11.7 Hz, H2-10) and 4.33, 4.24 (each 1H, J = 12.0 Hz, H2-19) (Table 1). Key cross-peaks of H2-3/C-4, -5 and -9, H-11/C-12, -13, and -19, and H-10/C-8, -9, and -11 in the HMBC spectrum of 1 established its gross structure as shown in Figure 2. All the configurations of Δ12, Δ14, and Δ16 of 1 were determined to be E by the conspicuous cross-peaks of 1098
dx.doi.org/10.1021/np400776y | J. Nat. Prod. 2014, 77, 1097−1101
Journal of Natural Products
Article
H-11/H-13, H-14/H-16, H-14/H 2 -19, and H-15/H-17 (Figure 2) together with distinctive JH‑14/H‑15 (14.6 Hz) and JH‑16/H‑17 (14.3 Hz). The relative configurations of C-11 and -20 were deduced to be erythro based on the coupling constant between H-11 and H-20 (J = 5.9 Hz), in contrast with that of the threo form (J = 7.5−8.0 Hz).9 Accordingly, the structure of 1 was elucidated as shown and was named trichoether A. The physical data of 2 were similar to those of 1 except for the appearance of two carbonyl groups, as judged from a characteristic absorption peak at 1714 cm−1 in its IR spectrum. UV λmax at 290 and 325 nm suggested the presence of a long conjugated olefinic functionality. When comparing 1H and 13C NMR data of 2 with those of 1, major differences were that the OH-20 in 1 was oxidized to give a ketone carbonyl (δC 206.4) in 2, and the oxymethylene-19 attached C-12 in 1 was oxidized to be an aldehyde group (δH 9.46; δC 191.8) (Table 1), as shown from key HMBC correlations of H3-21/C-11, -20, H-19/C-11, -12, and H-13/C-19 (Figure 3) and a sodium adduct at m/z
Figure 4. Key HMBC and NOESY of 3.
disappeared (Table 1). The relative configurations of α-oriented H-19 and H3-21 and β-oriented H-11 on the oxacyclopentane moiety were determined by key cross-peaks of H3-22/H-11, H3-21/H-10, and H3-22/H3-23 in the NOESY spectrum of 3 (Figure 4). Consequently, 3 was deduced to be the shown structure in Figure 1 and was named trichoether C. The 1H and 13C NMR data of 4 were almost identical with those of 3 except for the disappearance of a methoxyl signal at δH 3.51 and δC 55.8, and instead, mutually coupled oxymethylene resonances at δH 4.59 and 4.41 (each 1H, d, J = 13.5 Hz) and δC 67.2 were observed (Table 1), which implied 4 was a demethoxyl analogue of 3, which was also supported by a prominent sodium adduct at m/z 381.2040 (calcd for C22H30O4Na, 381.2042) in the HRESIMS of 4. The relative orientations of H-11 and H3-21 were at different phases, as judged by the key cross-peaks of H3-22/H-11 and H3-21/H-10 in the NOESY spectrum of 4. The key 13C resonances of the oxacyclopentane of 4 with those of the partial structural analogues lachnellins B and C10 showed the relative configuration of 4 was also consistent with that of lachnellin B (Figure 5). Compound 4 was determined to have the structure shown in Figure 1 and was named trichoether D.
Figure 3. Key HMBC of 2.
365.1728 (calcd for C21H26O4Na, 365.1729), 4 Da less than that of 1, in the HRESIMS of 2. In addition to the obvious NMR data shifts of H-11, H-21, C-11, and C-21 caused by the nearby functional group changes, the apparent downfield shifted signals of H-13, -15, -17 and C-13, -15, -17 in the NMR data of 2 were caused by the anisotropic and resonance effects of the aldehyde carbonyl located at C-19. The optical rotation of 2 was close to zero ([α]27D = ±0), indicating the presence of two almost equal amounts of racemic forms. The reason for the formation of a racemate is that the chiral center C-11 is neighboring a carbonyl group. The racemization will be spontaneous at room temperature. Hence, 2 was assigned as the shown structure in Figure 1 and was named trichoether B. Compound 3 was obtained as a colorless oil, and its IR absorptions at 3379, 1637, and 1588 and 1462 cm−1 indicated the presence of a phenol group. HRESIMS of 3 showed a prominent pseudomolecular ion [M + Na]+ at m/z 411.2147 (calcd for C23H32O5Na, 411.2147), indicating eight double-bond equivalences (DBE) in the structure of 3. Comparison of 13C NMR data of 3 with those of 1 showed that two additional carbon resonances observed in the 13C NMR coupled with the HSQC spectrum of 3 were attributable to two methoxyl carbons at δC 48.9 and 55.8. The monooxygenated carbons C-19 and -20 at δC 56.6 and 69.1, respectively, were replaced by two dioxygenated resonances at δC 103.1 and 108.8 in 3 (Table 1). The DBE of 3, one more than 1, suggested that an additional ring was present in the structure. Two methoxyls at δH 3.30 (H3-22) and 3.51 (H3-23) were deduced to be attached at C-20 and C-19, as evidenced from cross-peaks of H3-22/C-20 and H3-23/C-19 in the HMBC spectrum of 3 (Figure 4). The above data revealed an ether linkage between C-19 and -20 to form an oxacyclopentane, as corroborated by a key cross-peak of H-19/C-20 in the HMBC spectrum (Figure 4), which has resulted in two acetal functionalities as shown. The assigned skeleton was confirmed by 1H NMR of 3, in which H-19 shifted downfield to δH 5.53, and H-20
Figure 5. 13C NMR data of the oxacyclopentane moiety of 4 and lachnellins B and C.
To our knowledge, the skeletons of 1−4 are unique, and the related analogues of the partial structure of 1−4, lachnellins A−D, were previously isolated only from Lachnella sp.10 The formation of 3 and 4 from 1 is speculated to be derived from cyclization, oxidation, and methylation of the pyrophosphate of 1 (Figure 6). Compounds 1−4 and radicicol were evaluated for their growth-inhibitory activities against the A549 lung cancer cell line. They exhibited inhibitory activities, and their GI50 values were calculated to be 25.61, 19.32, 16.19, 24.31, and 1.43 μM, respectively. Under the same conditions, the GI50 value of 5fluorouracil was 4.55 μM.
■
EXPERIMENTAL SECTION
General Experimental Procedures. Optical rotations were measured on a JASCO P-2000 polarimeter (Tokyo, Japan). 1H and 13 C NMR were acquired on a Bruker Avance DRX-500 and AVIII-800 spectrometer (Ettlingen, Germany). Low-resolution and high-resolution mass spectra were obtained using an API4000 triple quadrupole mass 1099
dx.doi.org/10.1021/np400776y | J. Nat. Prod. 2014, 77, 1097−1101
Journal of Natural Products
Article
Pro-ODS-U column with MeOH−H2O (45:55, v/v) as eluent, 2 mL/min, to obtain 3,5-dihydroxytoluene (5.6 mg, tR = 12.89 min). Trichoether A (1): colorless oil; [α]27D +27.5 (c 0.55, MeOH); IR (ZnSe) νmax 3371, 2959, 2930, 2871, 1587, 1463, 1373, 1265, 1047, 990 cm−1; UV λmax (log ε, MeOH) 222 (3.99), 266 (4.42), 276 (4.54), 286 (4.46); 1H and 13C NMR data, see Table 1; ESIMS [M − H]− m/z 345; HREIMS [M − H]− m/z 345.2076 (calcd. for C21H29O4, 345.2066). Trichoether B (2): colorless oil; [α]27D ±0 (c 0.50, MeOH); IR (ZnSe) νmax 3339, 2957, 2930, 2870, 1714, 1666, 1598, 1459,1360, 1260, 1186, 1081, 999 cm−1; UV λmax (log ε, MeOH) 221 (4.05), 290 (4.10), 325 (4.31); 1H and 13C NMR data, see Table 1; ESIMS [M + Na]+ m/z 365; HRESIMS [M + Na]+ m/z 365.1728 (calcd for C21H26O4Na, 365.1729). Trichoether C (3): colorless oil; [α]27D −2.8 (c 0.50, MeOH); IR (ZnSe) νmax 3379, 2953, 1637, 1588, 1462, 1380, 1328, 1280, 1176, 1069, 990 cm−1; UV λmax (log ε, MeOH) 221 (3.90), 267 (4.40), 277 (4.53), 288 (4.47); 1H and 13C NMR data, see Table 1; ESIMS [M + Na]+ m/z 411; HRESIMS [M + Na]+ m/z 411.2147 (calcd for C23H32O5Na, 411.2147). Trichoether D (4): colorless oil; [α]27D +13.0 (c 0.50, MeOH); IR (ZnSe) νmax 3401, 2954, 2875, 2871, 1586, 1641, 1378, 1334, 1257, 1158, 1069, 1019 cm−1; UV λmax (log ε, MeOH) 221 (4.25), 248 (4.23), 277 (4.22), 289 (4.14); 1H and 13C NMR data, see Table 1; ESIMS [M + Na]+ m/z 381; HRESIMS [M + Na]+ m/z 381.2040 (calcd for C22H30O4Na, 381.2042). Growth Inhibitory Assay. Using the methods reported previously,11 A549 cells were seeded in 96-well plates in medium with 5% FBS. After 24 h, cells were fixed with 10% CCl3COOH to represent cell populations at the zero time of drug addition. After additional incubation of vehicle (0.1% DMSO) or 1−4 and radicicol for 48 h, cells were fixed with 10% CCl3COOH, and SRB was added to stain cells. Unbound SRB was washed out with 1% AcOH, and SRB-bound cells were solubilized with 10 mM Trizma base. The absorbance was read at 515 nm. Using the following absorbance measurements, such as time zero (T0), control growth (C), and cell growth in the presence of compound (Tx), the percentage growth was calculated at each of the compound concentration levels. Percentage growth inhibition was calculated as 100 − [(Tx − T0)/(C − T0)] × 100. Growth inhibition of 50% (GI50) is determined at the drug concentration that results in 50% reduction of total protein increase in control cells during the compound incubation.
Figure 6. Proposed biosynthetic pathways of 3 and 4 from 1. spectrometer (Applied Biosystems, Foster City, CA, USA) and a Synapt High Definition mass spectrometry system with an ESI interface and a TOF analyzer (Waters Corp., Manchester, UK), respectively. IR spectra were recorded on a JASCO FT/IR 4100 spectrometer (Tokyo, Japan). UV spectra were measured on a Thermo UV−VIS Heλios α spectrophotometer (Thermo Scientific, Waltham, MA, USA). Sephadex LH-20 (Amersham Biosciences, Filial Sverige, Sweden) and Diaion HP20 (Mitsubishi Chemical, Tokyo, Japan) were used for open-column chromatography. TLC was performed using silica gel 60 F254 plates (200 μm, Merck). A reflective index detector (Bischoff, Leonberg, Germany) was used in HPLC purification. Fermentation of Trichobotrys eff usa YMJ1179. Trichobotrys eff usa (Berkeley & Broome) Petch YMJ1179 was isolated and identified by one of us (Y.M.J.) and was deposited at the Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan. The sequence data of this fungal strain were submitted to GenBank, and the accession number for the nucleotide sequence was BankIt1711557 Seq1, KJ630313. The mycelium of this strain was inoculated into 5 L serum bottles, each containing 60 g of Bacto malt extract (Becton, Dickinson and Company, Sparks, USA) and 3 L of deionized water. The fermentation was conducted with aeration at 25−30 °C for 30 days. Extraction and Isolation. The filtered fermented broth (48.5 L) of T. ef f usa was partitioned three times with equal volumes of ethyl acetate, then concentrated in a vacuum to dryness (4.9 g). The crude extract was redissolved in 20 mL of MeOH, then applied onto a Sephadex LH20 column (3.0 cm o.d. × 68.5 cm) and eluted by MeOH with a flow rate of 1.9 mL/min. Each fraction (21 mL) collected was checked for its composition by TLC using CHCl3−MeOH (25:1, v/v) for development, and dipping in vanillin−sulfuric acid was used to detect compounds with similar skeletons. All the fractions were combined into nine portions, I−IX. Portion III (fr. 12, 13) was further separated by a Diaion HP-20 column (3.0 o.d. × 30 cm) with mixtures of H2O and MeOH as eluents in a stepwise gradient mode to give five subportions, III-1−III-5. Subportion III-5 (eluted by 100% MeOH) was purified finally by HPLC on a semipreparative Phenomenex Luna PFP column (5 μm, 10 × 250 mm, Torrance, CA, USA) eluted by 60% MeCN, 2 mL/min, affording 1 (30.7 mg, tR = 19.33 min), 2 (5.4 mg, tR = 27.63 min), 3 (7.8 mg, tR = 43.91 min), and 4 (10.5 mg, tR = 46.77 min). Portion IV (fr. 14−16) was rechromatographed on a Diaion HP-20 resin (3.0 cm o.d. × 30 cm) eluted with mixtures of H2O and MeOH in a stepwise gradient mode to give 10 subportions, IV-1−IV-10. Subportion IV-3 (eluted by 30% MeOH) was purified by HPLC on a semipreparative BIOSIL Pro-ODS-U column (5 μm, 10 × 250 mm, Biotic Chemical Co., Taipei, Taiwan) with MeOH−H2O (15:85, v/v) as eluent, 2 mL/min, to give coriloxin (10.3 mg, tR = 15.48 min). Subportion IV-9 (eluted by 90% MeOH) was purified by HPLC on a semipreparative Phenomenex Luna PFP column with MeCN−H2O (45:55, v/v) as eluent, 2 mL/min, to afford zythiostromic acid A (23.5 mg, tR = 26.89 min). Portion V (fr. 17−19) was purified by HPLC on a semipreparative Phenomenex Luna PFP column with MeCN−H2O (45:55, v/v) as eluent, 2 mL/min, to give radicicol (9.3 mg, tR = 18.81 min). The same portion was purified on a semipreparative BIOSIL
■
ASSOCIATED CONTENT
S Supporting Information *
1
H and 13C NMR spectra of the new compounds 1−4. This material is available free of charge via the Internet at http://pubs. acs.org.
■
AUTHOR INFORMATION
Corresponding Author
*Tel: 886-2-27361661, ext. 6156. E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS This work was supported by grants from the National Science Council of the Republic of China and Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH102-TDB-111-004). We thank Dr. S.-H. Wang of the Instrumentation Center of Taipei Medical University and Ms. S.-L. Huang of the Instrumentation Center of the College of Science, National Taiwan University, for the NMR data acquisition and Ms. Y.-C. Wu of the Small Molecule Metabolomics Core Facility, the Institute of Plant and Microbial Biology and Academia Sinica Scientific Instrument Center, Academia Sinica, for the MS data acquisition. 1100
dx.doi.org/10.1021/np400776y | J. Nat. Prod. 2014, 77, 1097−1101
Journal of Natural Products
■
Article
REFERENCES
(1) Bérdy, J. J. Antibiot. (Tokyo) 2012, 65, 385−395. (2) Wu, S. H.; Wang, Y. Z.; Chen, Y. P. The fungal barcoding work in Taiwan. Abstract, TELDAP International Conference; Academia Sinica: Taipei, Taiwan, 2011. (3) Petch, T. Revisions of Ceylon Fungi (Part VII)1924, 9, 119−184. (4) Hsiao, H. Y. Chemical constituents from the fermented broths of Nalanthamala psidii YMJ400, Trichobotrys ef f use YMJ1179 and Alveophoma caballeroi YMJ309 isolated in Taiwan. Master Thesis, Taipei Medical University: Taipei, Taiwan, 2012; p 3. (5) Shiono, Y.; Murayama, T.; Takahashi, K.; Okada, K.; Katohda, S.; Ikeda, M. Biosci. Biotechnol. Biochem. 2005, 69, 287−292. (6) Ayer, W. A.; Khan, A. Q. Phytochemistry 1996, 42, 1647−1652. (7) Garbaccio, R. M.; Stachel, S. J.; Baeschlin, D. K.; Danishefsky, S. J. J. Am. Chem. Soc. 2001, 123, 10903−10908. (8) Lee, T. H.; Chiou, J. L.; Lee, C. K.; Kuo, Y. H. J. Chin. Chem. Soc. 2005, 52, 833−841. (9) Joseph-Nathan, P.; Roman, L. U. Spectroscopy (Amsterdam, Netherlands) 1991, 9, 47−54. (10) Semar, M.; Anke, H.; Arendholz, W.-R.; Velten, R.; Steglich, W. Z. Naturforsch. C: Biosci. 1996, 51, 500−512. (11) Liang, W. L.; Hsiao, C. J.; Ju, Y. M.; Lee, L. H.; Lee, T. H. Chem. Biodiversity 2011, 8, 2285−2290.
1101
dx.doi.org/10.1021/np400776y | J. Nat. Prod. 2014, 77, 1097−1101
