Bioactive Azaphilone Derivatives from the Fungus Talaromyces

Jul 27, 2017 - Penicilazaphilones D and E: two new azaphilones from a sponge-derived strain of the fungus Penicillium sclerotiorum. Chao-Yi Wang , Jun...
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Bioactive Azaphilone Derivatives from the Fungus Talaromyces aculeatus Jie Ren,† Shuang-Shuang Ding,† Ao Zhu, Fei Cao,* and Hua-Jie Zhu* Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmaceutical Sciences, Hebei University, Baoding 071002, People’s Republic of China S Supporting Information *

ABSTRACT: Six new azaphilone derivatives, talaraculones A−F (1−6), together with five known analogues (7−11), were obtained from the saline soil-derived fungus Talaromyces aculeatus. The absolute configurations of 1 and 6 were assigned by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compounds 1 and 5 represent the first reported azaphilone derivatives with a C4 aliphatic side chain and a methylal group at C-3, respectively. Talaraculones A and B (1 and 2) exhibited stronger inhibitory activity against α-glucosidase than the positive control acarbose (IC50 = 101.5 μM), with IC50 values of 78.6 and 22.9 μM, respectively.

F

isolation, structure elucidation, absolute configurations, and biological activities of 1−11.

ungi have long been known for their ability to produce natural products with a wide variety of chemical structures and diverse biological activities.1−3 Among them, the fungi in the genus Talaromyces have produced various secondary metabolites with interesting biological activities and novel structures including sesquiterpenes,4 macrolides,5 and cyclic peptides.6 Bioactive azaphilone derivatives have been isolated from the fungi of the genus Talaromyces.7−11 Azaphilone derivatives exhibit a range of biological activities, including antibacterial, antifungal, antioxidant, cytotoxic, and anti-inflammatory.10,12 In our previous investigation into fungi collected from unusual environments, a series of bioactive azaphilone derivatives with cytotoxic, antibacterial, and antifungal activities have been isolated.13−16 From the saline soil-derived fungus Talaromyces aculeatu DS-62013, collected from Shandong Province of China, four azaphilone derivatives showing cytotoxicity were obtained from cultures grown in shaken Czapek−Dox medium.11 In order to maximize the ability of the fungus T. aculeatu to generate bioactive molecules, the fungus was grown using a number of conditions including varying the composition of culture medium, period of cultivation, pH, and temperature, knowing that the types of secondary metabolites produced are often altered in different cultivation conditions.17−19 During this process, we found the TLC and HPLC-UV profiles of the secondary metabolites produced differed from those previously observed when the fungus was cultured in a PDA medium under static conditions. Further investigation of the components led to the isolation of 11 azaphilone derivatives, including the six new talaraculones A−F (1−6) and five known compounds, pinazaphilone B (7),20 pinophilin B (8),21 Sch725680 (9),22 (−)-mitorubrin (10),23 and (−)-mitorubrinol (11).24 Some of these compounds showed inhibitory activity against α-glucosidase and antibacterial activity. Herein, we report the © XXXX American Chemical Society and American Society of Pharmacognosy

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RESULTS AND DISCUSSION Talaraculone A (1) was obtained as a yellow oil. The molecular formula was determined as C22H24O8 on the basis of positive HRESIMS, indicating 11 degrees of unsaturation. The IR absorption bands showed the presence of hydroxy (3351 cm−1), conjugated ester (1723 cm−1), and conjugated carbonyl groups (1646 cm−1). In the 1H and 13C NMR data of 1 (Tables 1 and 2), two aromatic proton signals at δH 6.16 (1 H, d, J = 2.0 Hz) and 6.10 (1 H, d, J = 2.0 Hz) and six aromatic carbon signals in the Received: January 12, 2017

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DOI: 10.1021/acs.jnatprod.7b00032 J. Nat. Prod. XXXX, XXX, XXX−XXX

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Table 1. 1H NMR Data (δ) of 1−6 (600 MHz, δ in ppm, J in Hz) position

1a

2a

3b

4a

5b

1 4 5 8 8a 9 10

3.76, dd (13.5, 10.9) 4.38, dd (10.9, 5.2) 5.72, brs 5.69, brs 5.19, d (10.0) 3.34, m 1.21, s 6.05, d (15.5)

3.92, dd (13.5, 10.9) 4.55, dd (10.9, 5.2) 6.27, brs 5.97, brs 5.33, d (9.9) 3.50, m 1.32, s 7.13, d (15.5)

3.90, dd (13.6, 11.0) 4.54, dd (11.0, 5.2) 6.71, brs 6.04, d (1.8) 5.30, d (9.8) 3.51, m 1.35, s

3.87, dd (13.2, 10.8) 4.43, dd (10.8, 5.4) 5.98, s 5.88, s 5.30, d (9.6) 3.47, m 1.39, s 4.83, s

1.37, s 6.32, d (15.6)

11 12 13 4′ 6′ 8′

6.34, dd (15.5, 5.3) 4.27, m 1.16, d (6.5) 6.10, d (2.0) 6.16, d (2.0) 2.48, s

6.55, dd (15.5, 7.8) 9.64, d (7.8)

3.75, dd (13.8, 10.8) 4.29, dd (10.8, 5.4) 5.49, brs 5.67, brs 5.19, d (10.2) 3.34, m 1.30, s 1.18, m 2.50, m 2.49, m

3.87, s

3.37, s 3.38, s

6.63, dt (15.6, 4.8) 4.25, m

6.24, d (2.0) 6.28, d (2.0) 2.59, s

6.31, brs 6.29, brs 2.58, s

6.13, d (2.4) 6.14, d (2.4)

a

3.62, s 6.23, d (2.4) 6.21, d (2.4) 2.52, s

6.20, brs 6.26, brs 2.58, s

6a 7.77, s 6.35, s 5.47, s 5.89, s

Recorded in CD3OD. bRecorded in CDCl3.

Table 2. 13C NMR Data (δ) of 1−6 (150 MHz, δ in ppm)

a

position

1a

2a

3b

4a

5b

6a

1 3 4 4a 5 6 7 8 8a 9 10 11 12 13 1′ 2′ 3′ 4′ 5′ 6′ 7′ 8′

69.3, CH2 161.7, C 105.2, CH 153.2, C 117.4, CH 197.4, C 75.0, C 76.6, CH 36.3, CH 19.7, CH3 123.3, CH 142.2, CH 68.3, CH 23.3, CH3 172.0, C 105.6, C 166.0, C 101.9, CH 164.2, C 112.8, CH 145.0, C 24.6, CH3

69.5, CH2 158.6, C 112.8, CH 150.7, C 121.2, CH 197.3, C 75.2, C 76.4, CH 36.2, CH 19.5, CH3 145.2, CH 132.2, CH 195.0, CH

68.3, CH2 165.8, C 101.3, CH 150.9, C 115.4, CH 195.1, C 74.1, C 74.7, CH 34.6, CH 20.2, CH3 29.7, CH2 30.8, CH2 172.7, C 51.9, CH3 170.5, C 105.3, C 164.3, C 102.2, CH 166.3, C 113.2, CH 145.2, C 25.2, CH3

70.1, CH2 151.3, C 111.0, CH 149.4, C 122.7, CH 197.3, C 75.2, C 76.3, CH 35.9, CH 19.7, CH3 163.5, C 53.7, CH3

68.4, CH2 160.3, C 102.4, CH 149.5, C 117.8, CH 194.9, C 74.2, C 74.6, CH 34.8, CH 20.2, CH3 99.6, CH 53.4, CH3 53.5, CH3

150.8, CH 157.0, C 109.5, CH 146.3, C 106.2, CH 199.9, C 75.2, C 76.1, CH 117.2, C 24.4, CH3 121.5, CH 139.1, CH 62.4, CH2

172.0, C 105.3, C 164.3, C 102.2, CH 166.3, C 113.2, CH 145.2, C 25.2, CH3

170.5, C 104.3, C 165.9, C 101.6, CH 161.3, C 112.0, CH 144.5, C 24.8, CH3

172.2, C 105.6, C 166.4, C 101.7, CH 164.1, C 112.7, CH 145.1, C 24.6, CH3

171.9, C 105.6, C 166.0, C 101.9, CH 164.2, C 112.6, CH 145.0, C 24.6, CH3

Recorded in CD3OD. bRecorded in CDCl3.

region of δC 101.9−166.0 indicated the existence of a 2,4-dihydroxy-6-methylbenzoic acid structural moiety.21−24 In the 13C NMR data of 1, one carbonyl group (δC 197.4) and two trisubstituted double bonds (δC 153.2 and 117.4) revealed that 1 shares the same azaphilone nucleus structure as Sch725680 (9), an azaphilone derivative obtained from the fungus Aspergillus sp.22 The main differences were the presence the [−CH CHCH(OH)CH3] fragment at C-3 in 1 instead of a propenyl group [−CHCHCH3] in 9, which was confirmed by the COSY cross-peaks of H-10/H-11/H-12/H-13 and the HMBC correlations from H-10 to C-3, C-4, and C-12 and from H-11 to C-3 and C-12, respectively (Figure 1). The coupling constant between H-10 and H-11 (J = 15.5 Hz) defined the double bond to be in the E orientation. Detailed analysis of the HSQC, COSY, and HMBC data allowed the assignment of all carbon and proton resonances of 1.

Figure 1. COSY and key HMBC correlations of 1.

The relative configuration of 1 was established on the basis of H−1H coupling constants and ROESY experiments. The coupling constant of J8,8a = 10.0 Hz indicated the trans-diaxial relationship of H-8/H-8a,21,22 whose cis-orientation should have the coupling constant of approximately J8,8a = 3.0 Hz.25 In the 1

B

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(Table 1) and ROESY spectra. As the ECD spectra of 2−5 closely matched that of 1 (Figure S2), the absolute configurations of 2−5 were assigned as (7S,8S,8aS). Talaraculone F (6), with the molecular formula of C21H20O8 based on HRESIMS, was also isolated as a yellow oil. Its NMR data featured an azaphilone derivative and closely resembled those of 1. The most obvious difference was the appearance of one trisubstituted double bond between C-1 and C-8a [δH 7.77 (1H, s, H-1); δC 150.8 (CH, C-1), 117.2 (C, C-8a)] in 6. This was confirmed by the HMBC correlations from H-1 to C-3 and from H-4 to C-8a. The ROESY correlation between H3-9 and H-8 suggested they should be placed on the same side of the molecule. The predicted ECD curve of (7S,8S)-6 calculated by a quantum method at the B3LYP/6-311+G(d)//B3LYP/ 6-31G(d) level was similar to the experimental one (Figure S3), indicating the (7S,8S) absolute configuration for 6. Azaphilone derivatives are a structurally variable family of fungal polyketide metabolites possessing a highly oxygenated pyranoquinone bicyclic core, which can be classified into 10 different structural groups.10,12 The names of azaphilones arose as a result of their affinity for ammonia: the pigments react with aminessuch as proteins, amino acids, and nucleic acidsto form red or purple vinylogous γ-pyridones due to the exchange of pyran oxygen for nitrogen.32 In our research, compounds 1−11 belong to the substructure type of bicyclic azaphilones with O-orsellinic acid or O-orsellinic acid derivatives.12 New compounds talaraculones A−F (1−6) possess a similar azaphilone nucleus, whose differences lay only within the respective aliphatic side chains connected at C-3. Among them, compound 1 represents the first reported azaphilone derivative with a C4 aliphatic side chain anchor at C-3. An azaphilone derivative with a methylal group at C-3 (5) is also reported for the first time. In previous literature, azaphilone derivatives were reported possessing enzyme inhibitory and antibacterial activities.10,12 Thus, the inhibitory activities against α-glucosidase and the antibacterial activities of 1−11 were tested. All of the compounds (1−11) were evaluated for their in vitro inhibitory activities against α-glucosidase.20 Among them, talaraculones A and B (1 and 2) were stronger than the positive control acarbose (IC50 = 101.5 μM), with IC50 values of 78.6 and 22.9 μM, respectively. The other compounds hardly displayed obvious activity (IC50 > 200 μM). The antibacterial activities of 1−11 against three Grampositive bacteria and three Gram-negative bacteria were tested.33 Only compounds 2 and 10 showed selective activities against the pathogenic bacteria Vibrio anguillarum, with the same MIC values of 0.26 μg/mL, stronger than the positive control ciprofloxacin (MIC = 0.52 μg/mL). The other compounds did not exhibit obvious activity (MIC > 8.28 μg/mL) in this test. Compounds 1−11 were also evaluated for their cytotoxicities against tumor cell lines. However, none of them displayed any activity against HL-60, HeLa, A549, and K562 cell lines. The above bioactivity results suggest that the side chain anchor at C-3 in azaphilone derivatives may play an important role in the inhibitory activities against α-glucosidase and antibacterial activities. The presence of a hydroxy group in the side chain (1) may increase the inhibitory activity against α-glucosidase. Compound 2 with the 12-aldehyde group showed the strongest activity against α-glucosidase and antibacterial activities, suggesting that the aldehyde group in the side chain might be an indispensable functional group.

ROESY spectrum of 1, the correlation between CH3-9 and H-8 was observed, which indicated the syn relationship between H-8 and CH3-9. Comparing computed electronic circular dichroism (ECD) and optical rotations (OR) with experimental results is a valid method to assign absolute configurations of natural products.26−30 Thus, the absolute configuration of 1 was investigated by quantum chemical calculations of their ECD and OR data. Conformational searches were performed using the MMFF94S force field for (7S,8S,8aS,12S)-1 and (7S,8S,8aS,12R)-1, respectively. All geometries (137 conformers for (7S,8S,8aS,12S)-1 and 146 for (7S,8S,8aS,12R)-1, respectively) with relative energy from 0 to 10 kcal/mol were used in optimizations at the B3LYP/6-31G(d) level using the Gaussian09 package.31 The B3LYP/6-31G(d)-optimized conformers (52 conformers for (7S,8S,8aS,12S)-1 and 44 for (7S,8S,8aS,12R)-1) with relative energy from 0 to 4.6 kcal/mol were then reoptimized at the B3LYP/6-311+G(d) level. ECD and OR computations for all B3LYP/6-311+G(d)-optimized conformers were carried out at the B3LYP/6-311++G(2d,p) level in the gas phase. Boltzmann statistics were performed for ECD simulations with a standard deviation of σ 0.4 eV. The predicted ECD spectrum for (7S,8S,8aS,12S)-1 looked similar to the experimental result of 1 (Figure S1, the red line). The computed ORs in the gas phase were +122.0 for (7S,8S,8aS,12S)1 and +215.0 for (7S,8S,8aS,12R)-1, and the experimental OR value was +82.6 in methanol. On the basis of both of the ECD and OR data, the absolute configuration of 1 was assigned as (7S,8S,8aS,12S). Talaraculones A−E (1−5) possessed an identical azaphilone nucleus, revealed by the common and highly conserved NMR signals of the azaphilone nuclei (Tables 1 and 2). The differences among these compounds lay only within the respective aliphatic side chains connected at C-3. The side chains of 2 and 3 were elucidated by comparisons with that of 1. In the side chain of 2, an aldehyde group (δH 9.64 (1 H, d, J = 7.8 Hz); δC 195.0) was present instead of an oxygenbearing methine carbon (δH 4.27, m, H-12; δC 68.3, CH, C-12) in 1, suggesting a [−CHCHCHO] side chain in 2. The COSY correlations of H-10/H-11 and HMBC correlations from H-10 to C-3 and C-12 and from H-11 to C-3 and C-12 confirmed the side chain assignment. In 3, compared with 1, an acetoxy group (δH 3.62, s; δC 172.7 and 51.9) was found in the side chain, and one double bond at C-10 and C-11 was absent in 3. The COSY correlation of H-10/H-11 and the HMBC correlations from H-10 to C-3 and C-12, from H-11 to C-3 and C-12, and from H-13 to C-12 indicated a methyl propionate [−CH2CH2COOCH3] group was connected at C-3 of 3. The side chain of 4 was determined by comparing its NMR with that of 3. The 1H and 13C NMR data (Tables 1 and 2) revealed that 4 has the same side chain structural features as those in 3, except for the absence of −CH2CH2− on the side chain in 4. The HMBC correlations from H-11 to C-10 and from H-4 to C-10 confirmed that the ester group was anchored at C-3 in 4. The side chain of 5 was assigned by comparing its NMR with that of 4. Two methoxyl groups [δH 3.38 (3H, s), 3.37 (3H, s); δC 53.5, 53.4] and a hemiketal methine carbon, C-10 (δC 99.6), were present in the side chain of 5, suggesting that an methylal group was connected to C-3. The HMBC correlations from H-11 and H-12 to C-10 and from H-10 to C-3 and C-4 confirmed the above deduction. The relative configurations of 2−5 were established to be the same as 1 by interpretation of the similar J8,8a coupling constants C

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1170, 1054 cm−1; 1H and 13C NMR data, see Tables 1 and 2; HRESIMS m/z 401.1225 [M + H]+ (calcd for C21H21O8, 401.1231). Talaraculone C (3): yellow oil; [α]20 D +40.0 (c 0.20, MeOH); UV (MeOH) λmax (log ε) 217 (4.10), 270 (3.89), 315 (4.07) nm; CD (MeOH) λmax (Δε) 234 (−3.06), 266 (2.81), 298 (−2.34), 356 (1.71) nm; IR (KBr) νmax 3353, 2925, 1723, 1647, 1594, 1446, 1255, 1166, 1055 cm−1; 1H and 13C NMR data, see Tables 1 and 2; HRESIMS m/z 433.1489 [M + H]+ (calcd for C22H25O9, 433.1493). Talaraculone D (4): white, amorphous powder; [α]20 D +45.0 (c 0.20, MeOH); UV (MeOH) λmax (log ε) 218 (4.25), 269 (4.09), 315 (4.25) nm; CD (MeOH) λmax (Δε) 217 (1.20), 228 (−1.01), 259 (6.74), 298 (−5.06), 322 (3.12) nm; IR (KBr) νmax 3321, 2927, 1725, 1650, 1606, 1446, 1252, 1167, 1054 cm−1; 1H and 13C NMR data, see Tables 1 and 2; HRESIMS m/z 405.1171 [M + H]+ (calcd for C20H21O9, 405.1180). Talaraculone E (5): yellow, amorphous powder; [α]20 D +60.0 (c 0.20, MeOH); UV (MeOH) λmax (log ε) 217 (4.30), 270 (4.14), 310 (4.31) nm; CD (MeOH) λmax (Δε) 217 (0.79), 236 (−2.26), 265 (3.75), 294 (−1.51), 318 (2.56) nm; IR (KBr) νmax 3378, 2935, 1720, 1648, 1617, 1457, 1257, 1169 cm−1; 1H and 13C NMR data, see Tables 1 and 2; HRESIMS m/z 421.1489 [M + H]+ (calcd for C21H25O9, 421.1493). Talaraculone F (6): yellow oil; [α]20 D +310.6 (c 0.23, MeOH); UV (MeOH) λmax (log ε) 219 (4.55), 270 (4.27), 366 (4.22) nm; CD (MeOH) λmax (Δε) 222 (−14.3), 256 (7.12), 278 (−42.3), 366 (14.9) nm; IR (KBr) νmax 3267, 2935, 1702, 1617, 1587, 1450, 1255, 1166 cm−1; 1H and 13C NMR data, see Tables 1 and 2; HRESIMS m/z 401.1222 [M + H]+ (calcd for C21H21O8, 401.1231). In Vitro Inhibition Studies on α-Glucosidase. The experiments were conducted according to referenced procedures,20 and acarbose was used as a positive control. Antibacterial Assays. Antibacterial activity was evaluated by the conventional broth dilution assay.33 Gram-positive bacteria (Micrococcus lysodeikticus, Bacillus cereus, Bacillus megaterium) and Gram-negative bacteria (Proteusbacillm vulgaris, Vibrio anguillarum, Vibrio parahemdyticus) were used, and ciprofloxacin was used as a positive control. The MICs of ciprofloxacin are 0.099 μg/mL against M. lysodeikticus, 0.430 μg/mL against B. cereus, and 1.655 μg/mL against B. megaterium. The MICs of ciprofloxacin are 0.199 μg/mL against P. vulgaris, 0.199 μg/mL against V. anguillarum, and 0.430 μg/mL against V. parahemdyticus. Cytotoxicity Assays. The cytotoxicities against human promyelocytic leukemia HL-60, human cervical carcinoma HeLa, human lung carcinoma A549, and human erythroleukemia K562 cell lines were evaluated according to a referenced method.34 Adriamycin was used as a positive control.

EXPERIMENTAL SECTION

General Experimental Procedures. Optical rotations were measured on an AA-55 Series automatic polarimeter. UV spectra were recorded on a Thermo Scientific Multiskan GO microplate spectrophotometer in MeOH. ECD spectra were obtained on a MOS450-SFM300 circular dichroism spectrometer. IR spectra were determined on a Nicolet-Nexus-470 spectrometer using KBr pellets. NMR spectra were acquired on a Bruker Avance III 600 MHz NMR spectrometer (600 MHz for 1H and 150 MHz for 13C), using tetramethylsilane as an internal standard. HRESIMS data were obtained from a Thermo Scientific LTQ Orbitrap XL spectrometer. HPLC was performed on a Shimadzu LC-20AT system using a C18 (Kromasil, 5 μm, 10 × 250 mm) column coupled with a SPD-M20A photodiode array detector. Silica gel (Qingdao Haiyang Chemical Group Co.; 200−300 mesh), octadecylsilyl silica gel (Japan, YMC Co.; 40−63 μm), and Sephadex LH-20 (Pharmacia, Co.) were used for column chromatography. Precoated silica gel plates (Yantai Zifu Chemical Group Co.; G60, F-254) were used for thin-layer chromatography. Fungal Material. The fungus Talaromyces aculeatus DS-62013 was collected from saline-alkali soil, Shandong Province, China, in April 2013. Identification of the fungus was based on previously reported data according to its morphological characteristics and a molecular biological protocol by 16S rRNA amplification and sequencing of the ITS region. Its 493 base pair ITS sequence had 99% sequence identity to that of Talaromyces aculeatus (GU384213). The sequence data had been submitted to GenBank with accession number KT726227. The strain was deposited in the Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmaceutical Sciences, Hebei University, Baoding, China. Extraction and Purification. Liquid fermentation (60 L, 1 L Erlenmeyer flasks each containing 400 mL of culture broth) of strain T. aculeatus was performed using PDA medium at 28 °C for 45 days. The cultured broth was filtered through cheesecloth to remove fungal mycelia. The filtrate was extracted using EtOAc at room temperature three times. The combined organic layers were evaporated under reduced pressure to afford a crude extract (58.0 g), which was further separated by silica gel column chromatography with CH2Cl2−MeOH to give five fractions (Fr.1−Fr.5). Fr.3 (8.0 g) was subjected to a silica gel column using gradient mixtures of dichloromethane and methanol to yield six subfractions (Fr.3-1−Fr.3-6). Fr.3-2 (1.3 g) was applied to Sephadex LH-20, eluted with CH2Cl2−MeOH (1:1), to afford seven subfractions (Fr.3-2-1−Fr.3-2-7). Fr.3-2-4 (0.5 g) was further separated by a silica gel column eluted with CH2Cl2−MeOH gradients (from 9:1 to 1:1) to produce compounds 1 (6.0 mg) and 10 (37.0 mg). Fr.3-2-5 (300 mg) was further separated by Sephadex LH-20 chromatography eluting with mixtures of petroleum ether−CH2Cl2−MeOH (2:1:1) and CH2Cl2−MeOH (1:1). Final purification by HPLC using a C18 (5 μm, 10 × 250 mm) column at a flow rate of 2.0 mL/min, eluting with 60% MeOH−H2O, afforded 4 (5.0 mg), 5 (5.5 mg), and 6 (8.0 mg), respectively. Fr.4 (6.0 g) was subjected to an ODS column eluting with MeOH−H2O gradients (from 1:9 to 1:0) to give five fractions (Fr.4-1− Fr.4-5). Fr.4-2 (0.52 g) was applied to Sephadex LH-20 (MeOH) and a silica gel column to give 2 (18 mg) and 9 (11.0 mg), respectively. Fr.4-4 (0.6 g) was applied to Sephadex LH-20 (MeOH) and then purified by HPLC eluting with 60% MeOH−H2O to give 3 (7.5 mg) and 8 (21.0 mg), respectively. Fr.5 (0.7 g) was further purified by MCI (eluted with MeOH−H2O, 30:70−100:0) and silica gel to yield 7 (9.8 mg) and 11 (20.0 mg), respectively. Talaraculone A (1): yellow oil; [α]20 D +82.6 (c 0.23, MeOH); UV (MeOH) λmax (log ε) 217 (4.39), 268 (4.16), 340 (4.25) nm; CD (MeOH) λmax (Δε) 224 (−2.04), 267 (1.68), 304 (−4.36), 374 (2.54) nm; IR (KBr) νmax 3351, 2925, 1723, 1646, 1583, 1454, 1257, 1167, 1056 cm−1; 1H and 13C NMR data, see Tables 1 and 2; HRESIMS m/z 417.1541 [M + H]+ (calcd for C22H25O8, 417.1544). Talaraculone B (2): yellow oil; [α]20 D +167.8 (c 0.20, MeOH); UV (MeOH) λmax (log ε) 218 (4.44), 267 (4.32), 351 (4.48) nm; CD (MeOH) λmax (Δε) 227 (−1.45), 255 (6.67), 305 (−5.26), 381 (3.80) nm; IR (KBr) νmax 3361, 2935, 2828, 1650, 1620, 1587, 1455, 1255,

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jnatprod.7b00032. 1 H NMR, 13C NMR, HSQC, COSY, HMBC, ROESY, and HRESIMS spectra of the new compounds (1−6) and the quantum mechanical calculation data for 1 and 6 (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (F. Cao). *E-mail: [email protected] (H.-J. Zhu). ORCID

Fei Cao: 0000-0002-5676-3176 Hua-Jie Zhu: 0000-0002-7263-2360 Author Contributions †

J. Ren and S.-S. Ding contributed equally to this work.

D

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Notes

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The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (No. 41606174), the Natural Science Foundation of Hebei Province of China (No. B2017201059), the Scientific Research Foundation of Hebei Educational Committee (ZD2017004), the Project of Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University), Ministry of Education of China (CMEMR2017-B07), and the High Performance Computer Center of Hebei University.

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DOI: 10.1021/acs.jnatprod.7b00032 J. Nat. Prod. XXXX, XXX, XXX−XXX