Polycyclic Polyprenylated Xanthones from Symphonia globulifera

Note pubs.acs.org/jnp

Polycyclic Polyprenylated Xanthones from Symphonia globulifera: Isolation and Biomimetic Electrosynthesis Kevin Cottet, Anne Neudörffer,* Marina Kritsanida, Sylvie Michel, Marie-Christine Lallemand, and Martine Largeron UMR COMETE 8638 CNRS - Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie de Paris, 4 Avenue de l’Observatoire, 75270 Paris Cedex 06, France S Supporting Information *

ABSTRACT: Two regioisomeric polycyclic xanthones, 3,16oxyguttiferone A (2) and 1,16-oxyguttiferone A (3), which are polyprenylated acylphloroglucinol-derived analogues, were isolated from the seeds of Symphonia globulifera, together with their presumed o-dihydroxybenzoyl precursor, guttiferone A (1). Anodic oxidation of 1 into the corresponding o-quinone species proved to be an efficient biomimetic method to generate xanthones 2 and 3 in high overall yield and to confirm their structures. Both compounds displayed cytotoxicity against the HCT 116 colon carcinoma cell line with IC50 values of 8 and 3 μM, respectively.

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umerous plant families, fungi, lichens, and bacteria produce xanthones that exhibit a broad range of biological activities.1 A variety of compounds functionalized with prenyl groups, 2,2-dimethylpyran or 2,2,3-trimethylfuran moieties, and caged-xanthones have been isolated from the Clusiacae.2,3 Other derivatives, found mainly in the Garcinia,4 Symphonia, 5 and Calophyllum genera, 6 possess the bicyclo[3.3.1]nonane-1,3,9-trione skeleton characteristic of the polycyclic polyprenylated acyl phloroglucinols (PPAPs) and have been found to display both cytotoxic effects against human cell lines and antiplasmodial activity. In Garcinia cambogia, two related regioisomers, oxyguttiferones K and K2 (Figure 1), have been characterized: one possesses a linkage involving O-3 and C-16 of the acylphloroglucinol core, while the second includes O-1 and C-16.4d Unlike xanthones possessing various polyoxygenated rings or PPAPs substituted at C-2 by a benzoyl group, all of these derivatives possess a 3,4-dihydroxybenzoyl moiety.

Because 3,16-linked PPAPs co-occur with the corresponding o-dihydroxybenzoyl PPAPs in Calophyllum thorelii and most Garcinia species, several hypotheses have been advanced to explain their formation, but in most cases, the mechanism requires an oxidation step.7 Such an oxidative approach was confirmed by the transformation of garcinol into 1,16- and 3,16-oxygarcinols8 in the presence of radical initiators. However, these xanthones were obtained in 5−10% yields, showing that a different oxidation mechanism could be implicated in the formation of polycyclic polyprenylated xanthones. Recently, we reported a yeast-catalyzed oxidation of guttiferone A, which is a PPAP that is abundant in the seeds of Symphonia globulifera,9 regioselectively providing 3,16oxyguttiferone A (2).10 Because oxidation of 2,3′,4,6-tetrahydroxybenzophenone gave 1,3,5- or 1,3,7-trihydroxyxanthone, depending on the cytochrome P450 used,11 we attempted to establish whether 2 and possibly another regioisomer were present in S. globulifera seeds and whether they could be generated through the cyclization of the o-quinone arising from 1. Chromatographic separation of the methanolic extract led to the isolation of guttiferone A (1), 3,16-oxyguttiferone A (2), and the novel 1,16-linked regioisomer 3. To elucidate the structure of 3 and validate the biosynthetic hypothesis, a biomimetic electrochemical synthesis was developed, generating 3,16- and 1,16-oxyguttiferones A (2 and 3), which were further evaluated for their cytotoxic effects.

Figure 1. Structures of oxyguttiferones K and K2.

Received: March 19, 2015

© XXXX American Chemical Society and American Society of Pharmacognosy

A

DOI: 10.1021/acs.jnatprod.5b00239 J. Nat. Prod. XXXX, XXX, XXX−XXX

Journal of Natural Products

Note

Table 1. 1H (300 MHz) and 13C (75 MHz) NMR Spectroscopic Data of Compound 3 in Methanol-d4

Seeds of S. globulifera L.f. collected in the humid equatorial forest of Macouria in French Guiana were extracted with MeOH. After partitioning between EtOAc and H2O, the organic extract was subjected to preparative reversed-phase HPLC chromatography, yielding compounds 1−3. The 1H NMR spectra of compound 1 recorded in methanol-d4 + 0.1% TFA and pyridine-d5, as well as specific rotation ([α]20D +34), were in accordance with those of guttiferone A,12,13 which was recently obtained by total synthesis.14 Moreover, compound 2 was identified as 3,16-oxyguttiferone A (Figure 2) by comparing the NMR spectra and specific rotation with reported data.10

position

Figure 2. Structures of guttiferone A (1) and 3,16-oxyguttiferone A (2).

Compound 3 exhibited an HRESIMS ion at m/z 599.3369 ([M − H]−, calcd 599.3373), which in conjunction with 13C NMR data corresponded to a molecular formula of C38H48O6, which is identical to those of 2 and oxyguttiferone K2. 1H and 13 C NMR data revealed that 3 also had a polycyclic xanthone core derived from an appropriate PPAP (Table 1). However, the NMR data of 3 showed aromatic protons at δH 7.45 and 6.93 and an HMBC correlation from H-7 to C-1 at δC 177.3, whereas the data of compound 2 were characterized by aromatic protons at δH 7.45 and 6.99 and an HMBC correlation from H-7 to C-1 at δC 194.4. Therefore, compound 3 resulted from a 1,16-ring closure (Figure 3). COSY and HMBC spectra indicated the presence of a 4-methylpent-3-enyl group, in addition to prenyl units at C-4, C-6, and C-8 (Figure 4). Moreover, NOESY correlations from H-22 to H-24, H-7α (δH 2.39) to H-29, and H-7β (δH 2.14) to H-22 revealed that the Me-22 and C-6 prenyl groups were located on the same side of the cyclohexanone ring, while the chains linked to C-4, C-5, and C-8 were on the opposite side. Accordingly, because it exhibits a positive specific rotation, [α]20D = +53, the structure of compound 3 is similar to that of oxyguttiferone K2. Nevertheless, 3 differed in terms of the chemical shift of the C-22 methyl group resonating at δH 1.21 instead of δH 0.81 in oxyguttiferone K2. To test the hypothesis of a biogenetic transformation of guttiferone A (1) into 3,16-oxyguttiferone A (2) and 1,16oxyguttiferone A (3), we aimed at developing a biomimetic synthesis that could generate both through cyclization of the corresponding o-quinone (Scheme 1). Previous attempts to oxidize the o-dihydroxybenzoyl moiety of PPAPs involved garcinol8 or a mixture of guttiferone E and its regioisomer, xanthochymol. In the presence of NaIO4, the guttiferone E/ xanthochymol mixture gave the corresponding o-quinones as the sole products in 55% overall yield.15 Over the past few years, electroorganic methods have proved to be an environmentally friendly and efficient tool to access various complex molecules.16 In particular, the anodic oxidation of phenol

δC, type

1 2 3 4 5 6 7

177.3, 118.6, 194.0, 71.0, 51.1, 38.7, 37.5,

C C C C C CH CH2

8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38

55.5, C 206.1, C 172.5, C 117.1, C 108.3, CH 145.7, C 150.2, C 102.4, CH 153.4, C 25.2, CH2 119.2, CH 134.0, C 17.0, CH3 24.7, CH3 17.4, CH3 35.2, CH2 28.6, CH2 123.6, CH 132.5, C 16.33, CH3 24.3, CH3 30.7, CH2 118.8, CH 134.4, C 17.0, CH3 24.8, CH3 22.4, CH2 123.6, CH 131.6, C 24.5, CH3 16.27, CH3

δH (J in Hz)

HMBC 7

1.95, m 2.14, dd (14.5, 6.5) 2.39, d (14.5)

7.45, s

6.93, s 2.65, m 4.75, t (6.1) 1.73, s 1.63, s 1.21, s 1.28−1.43, m 1.93−1.95, m 4.81, t (6.4) 1.02, 1.55, 2.74, 5.08,

s s m m

1.82, 1.57, 1.94, 5.11,

s s m m

1.71, s 1.63, s

17 22 7, 22 22, 24 1, 24 1, 5, 8, 9 7, 29 7, 29 12 15 10, 13, 16 12, 15 15 11, 13, 14 12 3 21 21 18, 19, 21 20 4, 5, 6, 23 22 6, 7 28 28 25, 26, 28 27 8, 9, 30 29, 32 32, 33 30, 31, 33 31, 32

38 37

Figure 3. Structure of compound 3.

provides a powerful means of C−C or C−O bond formation for the synthesis of natural scaffolds.17 Electrogenerated quinone species can further be engaged in diverse chemical reactions, such as cycloaddition, Michael addition, or cyclization.18 Therefore, a biomimetic electrochemical synthesis toward 3,16- and 1,16-oxyguttiferones A was investigated. Because the intramolecular cyclization of the enolate form of o-quinone species would be easier than that of the neutral species, the redox behavior of guttiferone A (1) was examined B



Note

Figure 5. Cyclic voltammogram of guttiferone A (1) (0.5 mM) at a glassy carbon electrode in MeOH containing LiClO4 (5 mM) and Me4N+OH− (0.5 mM). Scan rate: 0.1 V s−1.

Figure 4. Key COSY, HMBC, and NOESY correlations of compound 3.

Scheme 1. Proposed Mechanism of Formation of Oxyguttiferones A

Figure 6. HPLC profiles of (a) the extract of the seeds of Symphonia globulifera and (b) the electrolysis solution. Column, Zorbax SB-C18 (150 mm × 4.6 mm, 5 μm); eluent, MeCN/(H2O + 0.1% HCO2H) from 75:25 to 95:5 over 45 min; detection, UV 254 nm; flow rate, 1 mL min−1.

in the presence of a stoichiometric amount of tetramethylammonium hydroxide (Me4N+OH−). The cyclic voltammogram of guttiferone A enolate 1− recorded in MeOH containing LiClO4 as the supporting electrolyte showed an irreversible two-electron anodic peak Pa at +0.60 V vs Ag/AgCl, which was preceded by a weak peak Pa′ at +0.15 V vs Ag/AgCl (Figure 5). The anodic peak Pa was assigned to the formation of o-quinone species, while Pa′ could be attributed to the oxidation of the phenolate−enolate bianion 12−, as confirmed by the addition of a second equivalent of Me4N+OH−. Regarding the other odioxyxanthones,19 the neutral form of oxyguttiferone A (2) was also electroactive at a potential higher than +0.60 V vs Ag/ AgCl. When the oxidation of enolate 1− was performed at Eox = +0.35 V vs Ag/AgCl, i.e., at a controlled potential that prevents the electroxidation of the expected oxyguttiferones, a coulometric value of 2.1 ± 0.1 F was recorded for the number of electrons involved in the exhaustive oxidation of one mole of anion 1−. The HPLC profile of the electrolysis solution showed the presence of two products that were generated in a 2:1 ratio and were characterized by retention times similar to those of compounds 2 and 3 isolated from the seeds of S. globulifera (Figure 6). After preparative HPLC, the 1H and 13C NMR

spectra of each of these compounds, isolated in yields of 39% and 19%, respectively (Table 2, entry 1), were identical to those of natural products 2 and 3. Depending on the keto−enolate tautomeric equilibrium, two o-quinone species could be electrogenerated from guttiferone A, leading to 3,16- and 1,16-linked PPAPs. Because the C-4, C5, C-6, and C-8 stereogenic centers are not affected by cyclization, compound 3 was identified as 1,16-oxyguttiferone A, and its relative configuration was found to be the same as that of guttiferone A. When a 100-fold excess of LiClO4 was introduced to optimize the electrolysis conditions, the oxidation time significantly increased. Assuming that the formation of a lithiated intermediate of a PPAP enolate20 induced anode passivation, the influence of the supporting electrolyte was investigated. The replacement of LiClO4 with LiCl had no effect on the oxidation time (Table 2, entry 2), while increasing the cation radius (entries 2−4) extended the duration of C



Note

galvanostat. The working electrode used in the voltammetry measurements was a glassy carbon disk, which was carefully polished before each voltammogram with an aqueous alumina suspension. All potentials were relative to the Ag/AgCl electrode, and the counter electrode was a platinum electrode. Controlled-potential electrolysis was carried out with a divided cell. The working electrode, a cylindrical graphite carbon electrode (6 cm diameter and 2.5 cm height), was immersed in the anodic compartment, and the counter-electrode, a platinum plate, was placed on the glass frit separating the anodic and cathodic compartments. Plant Material. The seeds of S. globulifera L.f. were collected in November 2012 from the humid equatorial forest of Macouria in French Guiana (4°55′7.4634″ N, 52°39′58.464″ W). The plant was identified by Dr. G. Odonne, and a voucher specimen (Odonne 770) was deposited at the French Guiana herbarium. Extraction and Isolation of Guttiferone A (1) and Compounds 2 and 3. Dried seeds (180 g) of S. globulifera were ground and extracted with distilled MeOH (2 × 1 L) at room temperature to give 32 g of methanolic extract. This extract was dissolved in EtOAc (500 mL) and washed with distilled H2O (500 mL). The evaporation of the organic phase afforded 26 g of extract, which was subjected to a silica gel column (CH2Cl2/MeOH, 98:2), yielding 300 fractions of 20 mL. The fractions were combined on the basis of TLC analysis and purified by further chromatography. Gutttiferone A (1) (1.07 g, 0.59%) was separated from the most polar fractions by flash chromatography with cyclohexane/EtOAc, 3:2. From the collected fractions (3.2 g) showing the presence of compounds with similar Rf compared to the yeast-synthesized oxyguttiferone A 2, 300 mg was purified by preparative HPLC (flow rate 20 mL/min, eluent MeCN/ H2O, 70:30 → 100:0 over 60 min), to afford compounds 2 (36 mg) and 3 (9 mg). General Experimental Procedure for the Electrosynthesis of Compounds 2 and 3. Guttiferone 1 (60.7 mg, 0.1 mmol) was dissolved in MeOH (200 mL) containing Et4N+Cl− (165.5 mg, 1 mmol) and Me4N+OH− (42 μL of a 25 wt % solution in MeOH, 0.1 mmol). The resulting solution was oxidized under N2 at room temperature at a graphite carbon electrode (Eox = +0.35 V vs Ag/ AgCl). After the oxidation was complete (2.0 F mol−1), i.e., when the decay of the current exceeded 95%, the methanolic solution was poured into an aqueous HCl solution (0.1 mol L−1, 100 mL). The resulting aqueous MeOH solution was concentrated to 100 mL under reduced pressure at 40 °C and extracted with EtOAc (2 × 50 mL). The organic layer was dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure at 40 °C. The crude residue was purified by preparative HPLC (flow rate 20 mL/min, eluent MeCN/ (H2O + 0.1% HCO2H), 75:25 → 95:5 over 50 min), to afford compounds 2 (32 mg, 53%) and 3 (15 mg, 25%) as yellow oils. 3,16-Oxy-guttiferone A (2): yellow oil; [α]20D = +48 (c 1, MeOH); IR (neat) νmax 3225, 2968, 2915, 2854, 1735, 1686, 1616, 1512, 1465, 1382, 1292, 1185, 1143, 1111, 984, 830 cm−1; 1H NMR (methanol-d4, 300 MHz) 7.45 (1H, s, H-16), 6.99 (1H, s, H-13), 5.22 (1H, t, J = 7.6 Hz, H-30), 5.11 (1H, t, J = 6.7 Hz, H-35), 4.85 (1H, m, H-25), 4.65 (1H, m, H-18), 2.95 (1H, m, H-17), 2.87 (1H, m, H-17), 2.53 (2H, m, H-29), 2.08 (2H, m, H-7), 1.98 (2H, m, H-34), 1.92 (1H, m, H-24), 1.77 (1H, m, H-24), 1.88 (1H, m, H-6), 1.74 (3H, s, H-20), 1.71 (9H, s, H-32, H-33, H-38), 1.64 (6H, s, H-28, H-37), 1.53 (1H, m, H-23), 1.42 (1H, m, H-23), 1.38 (3H, s, H-21), 1.35 (3H, s, H-27), 1.29 (3H, s, H-22); 13C NMR Jmod (75 MHz, methanol-d4) 207.4 (C, C-9), 194.4 (C, C-1), 179.5 (C, C-3), 174.5 (C, C-10), 155.0 (C, C-14), 151.2 (C, C-16), 147.2 (C, C-13), 136.2 (C, C-19), 135.5 (C, C-31), 134.1 (C, C-26), 133.0 (C, C-36), 125.0 (CH, C-35), 124.6 (CH, C25), 120.8 (CH, C-30), 119.7 (CH, C-18), 119.0 (C, C-2), 118.0 (C, C-11), 109.5 (CH, C-12), 104.0 (CH, C-15), 66.8 (C, C-8), 65.0 (C, C-4), 52.0 (C, C-5), 41.6 (CH, C-6), 39.2 (CH2, C-7), 37.9 (CH2, C23), 30.4 (CH2, C-24), 30.3 (CH2, C-29), 27.4 (CH2, C-17), 26.3 (CH3, C-38), 26.1 (CH3, C-28), 26.0 (CH3, C-33), 25.9 (CH3, C-21), 23.9 (CH3, C-34), 20.4 (CH3, C-22), 18.7 (CH3, C-20), 18.1 (CH3, C32), 18.0 (CH3, C-27), 17.8 (CH3, C-37); HRESIMS m/z [M − H]− 599.3397 (calcd for 599.3373). The physical data were found to be in agreement with reported data.10

Table 2. Influence of the Supporting Electrolyte on the Electrochemical Oxidation of Guttiferone A (1)a entry

supporting electrolyte

charge (F mol−1)

time (h)

2 (%)b

3 (%)b

2+3 (%)

1 2 3 4 5 6

LiClO4 LiCl NaCl KCl CsCl Et4N+Cl−

2.1 2.1 2.0 1.9 2.3 2.0

7.5 7.5 10 16 7.5 4.5

39 45 53 45 51 53

19 22 23 21 23 25

58 67 76 66 74 78

[1] = 0.5 mM in MeOH, [Et4N+OH−] = 0.5 mM, [supporting electrolyte] = 5 mM, carbon anode, Eox = +0.35 V vs Ag/AgCl. b Isolated yield after preparative HPLC. a

electrolysis. However, the anode passivation disappeared when larger cations, such as Cs+ or Et4N+, were used. Better results were then obtained in the presence of Et4N+Cl−, generating xanthones 2 and 3 in 78% overall yield after 4.5 h. Guttiferone A (1) and 3,16- and 1,16-oxyguttiferones A (2 and 3) were tested for cytotoxicity against the HCT 116 colon adenocarcinoma cell line using an MTS assay. These compounds displayed IC50 values of 6, 8, and 3 μM, respectively, which were similar to the reported values for oblongifolins F and G and slightly lower than that of garciesculentone B.4f,h In summary, two regioisomeric oxyguttiferones A (2 and 3) were isolated along with guttiferone A (1) from the seeds of S. globulifera, and their relative configurations were assigned by comparison with samples obtained through yeast-catalyzed and/or electrochemical oxidation. The anodic generation of the o-quinone of guttiferone A enolate 1− was found to be an efficient biomimetic-type method to simultaneously produce 2 and 3 in high overall yield, providing supporting evidence for a biosynthetic pathway involving an o-quinone species as the intermediate. Because these oxyguttiferones A also displayed cytotoxicity against the HCT 116 colon adenocarcinoma cell line, efforts will be made to extend this electrochemical methodology to other structural modifications of similar odihydroxybenzoyl PPAPs.

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EXPERIMENTAL SECTION

General Experimental Procedures. Optical rotations were measured at 20 °C using a PerkinElmer 341 polarimeter. IR spectra were recorded with a PerkinElmer 65 FT-IR spectrometer. 1H NMR and 13C NMR spectra were recorded on a Bruker AC-300 instrument operating at 300 and 75 MHz. 2D NMR experiments (COSY, NOESY, HSQC, HMBC) were performed on a Bruker Avance 400 spectrometer using standard pulse sequences. Chemical shifts are expressed as δ units (part per million) using the peak signals of the solvent as internal reference. HRESIMS data were recorded on a QToF1 mass spectrometer equipped with an electrospray ionization (ESI) source in both positive and negative modes. Analytical TLC was carried out on silica gel (Macherey-Nagel Alugram Sil G/UV 254, 0.25 mm). Flash chromatography was performed with silica gel (SDS Chromatogel 60, 20−45 μm). Analytical HPLC was performed on a LaChrom Elite system controlled by EZChrom Elite 3.3 software, with a Zorbax C18 SB-C18 (150 mm × 4.6 mm, 5 μm) column and a 20 μL loop injector. Detection was achieved at 254 nm. Analyses were carried out at 1 mL/min using a linear gradient elution with MeCN as solvent A and H2O + 0.1% HCO2H as solvent B (75−95% A, 0−45 min; 95% A, 20 min). Preparative HPLC was performed at 20 mL/min on a C18 Pursuit column (250 × 30 mm, 10 μm) with an Armen pump and a 10 mL loop injector. Detection was achieved at 254 nm. Cyclic voltammetry and controlled potential electrolysis were conducted with a Metrohm Autolab model PGSTAT302N potentiostat/ D



Note

1,16-Oxy-guttiferone A (3): yellow oil; [α]20D = +53 (c 1, MeOH); IR (neat) νmax 3225, 2967, 2916, 2856, 1732, 1678, 1617, 1514, 1463, 1382, 1287, 1225, 1183, 1142, 1094, 1058, 984, 954, 886, 832 cm−1; 1 H NMR (300 MHz, methanol-d4) and 13C NMR Jmod (75 MHz, methanol-d4) data, see Table 1; HRESIMS m/z [M − H]− 599.3369 (calcd 599.3373). Cytotoxicity Assay. The cytotoxic activities of compounds 1−3 against the HTC 116 cell line were evaluated using the CIBLOT platform of IFR 141, Faculté de Pharmacie, University Paris 11 (Chatenay Malabry). The human cell line HCT 116 (colon adenocarcinoma) was obtained from ATCC (CCL-247) and grown in RPMI medium supplemented with 10% fetal calf serum in the presence of penicillin, streptomycin, and fungizone at 37 °C in a humidified atmosphere containing 5% CO2. Cells were plated (2500 cells/well, Biomek 2000 Beckman-Coulter) in 96-well tissue culture plates in 200 μL of medium and treated 24 h later with 2 μL of stock solutions of the compounds dissolved in DMSO at concentrations ranging from 5 nM to 100 μM. Controls received the same volume of DMSO (1% final volume). After 72 h of exposure, MTS reagent (Promega) was added, and the whole was incubated for 3 h at 37 °C. The absorbance was monitored at 490 nm, and results are expressed as the inhibition of cell proliferation calculated as the ratio (1 − (OD 490 treated/OD 490 control)) × 100. The IC50 values, which were defined as the concentration of compounds inhibiting 50% of cell proliferation, were determined in separate duplicate experiments.

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Chang, D. C.; Luo, K. Q.; Xu, H.-X. J. Nat. Prod. 2009, 72, 130−135. (d) Masullo, M.; Bassarello, C.; Bifulco, G.; Piacente, S. Tetrahedron 2010, 66, 139−145. (e) Xia, Z.-X.; Zhang, D.-D.; Liang, S.; Lao, Y.-Z.; Zhang, H.; Tan, H.-S.; Chen, S.-L.; Wang, X.-H.; Xu, H.-X. J. Nat. Prod. 2012, 75, 1459−1464. (f) Feng, C.; Huang, S.-X.; Gao, X.-M.; Xu, H.-X.; Luo, K. Q. J. Nat. Prod. 2014, 77, 1111−1116. (g) Zhang, H.; Zhang, D.-D.; Lao, Y.-Z.; Fu, W.-W.; Liang, S.; Yuan, Q.-H.; Yang, L.; Xu, H.-X. J. Nat. Prod. 2014, 77, 1700−1707. (h) Xu, H.; Zhang, H.; Xi, Z.; Tan, H.; Chen, K.; Bian, Z.; Yang, D.; Chen, S.; Lu, A.; Chan, A. S. C. U.S. Patent 0,194,498, 2014. (5) Marti, G.; Eparvier, V.; Moretti, C.; Prado, S.; Grellier, P.; Hue, N.; Thoison, O.; Delpech, B.; Guéritte, F.; Litaudon, M. Phytochemistry 2010, 71, 964−974. (6) Nguyen, L.-T. T.; Nguyen, H. T.; Barbič, M.; Brunner, G.; Heilmann, J.; Pham, H. D.; Nguyen, D. M.; Nguyen, L.-H. D. Tetrahedron Lett. 2012, 53, 4487−4493. (7) Fromentin, Y.; Cottet, K.; Kritsanida, M.; Michel, S.; GaboriaudKolar, N.; Lallemand, M.-C. Planta Med. 2015, 81, 95−107. (8) (a) Sang, S.; Pan, M.-H.; Cheng, X.; Bai, N.; Stark, R. E.; Rosen, R. T.; Lin-Shiau, S.-Y.; Lin, J.-K.; Ho, C.-T. Tetrahedron 2001, 57, 9931−9938. (b) Sang, S.; Liao, C.-H.; Pan, M.-H.; Rosen, R. T.; LinShiau, S.-Y.; Lin, J.-K.; Ho, C.-T. Tetrahedron 2002, 58, 10095−10102. (9) (a) Fromentin, Y.; Gaboriaud-Kolar, N.; Lenta, B. N.; Wansi, J. D.; Buisson, D.; Mouray, E.; Grellier, P.; Loiseau, P. M.; Lallemand, M.-C.; Michel, S. Eur. J. Med. Chem. 2013, 65, 284−294. (b) Cottet, K.; Genta-Jouve, G.; Fromentin, Y.; Odonne, G.; Duplais, C.; Laprévote, O.; Michel, S.; Lallemand, M.-C. Phytochemistry 2014, 108, 102−108. (10) Fromentin, Y.; Grellier, P.; Wansi, J. D.; Lallemand, M.-C.; Buisson, D. Org. Lett. 2012, 14, 5054−5057. (11) Peters, S.; Schmidt, W.; Beerhues, L. Planta 1998, 204, 64−69. (12) Gustafson, K. R.; Blunt, J. W.; Munro, M. H. G.; Fuller, R. W.; McKee, T. C.; Cardellina, J. H., II; McMahon, J. B.; Cragg, G. M.; Boyd, M. R. Tetrahedron 1992, 48, 10093−10102. (13) (a) Lenta, B. N.; Noungoue, D. T.; Devkota, K. P.; Fokou, P. A.; Ngouela, S.; Tsamo, E.; Sewald, N. Acta Crystallogr., Sect. E: Struct. Rep. Online 2007, E63, o1282−o1284. (b) Martins, F. T.; Cruz, J. W., Jr.; Derogis, P. B. M. C.; dos Santos, M. H.; Veloso, M. P.; Ellena, J.; Doriguetto, A. C. J. Braz. Chem. Soc. 2007, 18, 1515−1523. (14) Horeischi, F.; Biber, N.; Plietker, B. J. Am. Chem. Soc. 2014, 136, 4026−4030. (15) Roux, D.; Hadi, H. A.; Thoret, S.; Guénard, D.; Thoison, O.; Païs, M.; Sévenet, T. J. Nat. Prod. 2000, 63, 1070−1076. (16) (a) Schäfer, H. J. C. R. Chim. 2011, 14, 745−765. (b) Francke, R.; Little, R. D. Chem. Soc. Rev. 2014, 43, 2492−2521. (c) Waldvogel, S. R.; Janza, B. Angew. Chem., Int. Ed. 2014, 53, 7122−7123. (17) (a) Yamamura, S.; Nishiyama, S. Synlett 2002, 4, 533−543. (b) Sumi, T.; Saitoh, T.; Natsui, K.; Yamamoto, T.; Atobe, M.; Einaga, Y.; Nishiyama, S. Angew. Chem., Int. Ed. 2012, 51, 5443−5446. (c) Elsler, B.; Schollmeyer, D.; Dyballa, K. M.; Franke, R.; Waldvogel, S. R. Angew. Chem., Int. Ed. 2014, 53, 5210−5213. (18) For some recent examples, see: (a) Nematollahi, D.; Rafiee, M. Green Chem. 2005, 7, 638−644. (b) Xu, D.; Chiaroni, A.; Largeron, M. Org. Lett. 2005, 7, 5273−5276. (c) Zeng, C.-C.; Liu, F.-J.; Ping, D.-W.; Hu, L.-M.; Cai, Y.-L.; Zhong, R.-G. J. Org. Chem. 2009, 74, 6386− 6389. (d) Zeng, C.-C.; Ping, D.-W.; Hu, L.-M.; Song, X.-Q.; Zhong, R.-G. Org. Biomol. Chem. 2010, 8, 2465−2472. (e) Martinez, C.-M.; Neudörffer, A.; Largeron, M. Org. Biomol. Chem. 2012, 10, 3739− 3748. (f) Nematollahi, D.; Davarani, S. S. H.; Mirahmadpour, P. ACS Sustainable Chem. Eng. 2014, 2, 579−583. (19) Nishihama, Y.; Amano, Y.; Ogamino, T.; Nishiyama, S. Electrochemistry 2006, 8, 609−611. (20) Hayes, C. J.; Simpkins, N. S. Org. Biomol. Chem. 2013, 11, 8458−8462.

ASSOCIATED CONTENT

S Supporting Information *

1D and 2D NMR spectra of the products. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jnatprod.5b00239.

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AUTHOR INFORMATION

Corresponding Author

*Tel: (+) 33 1 53 73 96 27. Fax: (+) 33 1 44 07 35 88. E-mail: anne.neudorff[email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS K.C. thanks the Université Paris Descartes, Sorbonne Paris Cité, for a Ph.D. grant. We thank C. Duplais and G. Odonne for providing the logistics needed to harvest the plant material.

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REFERENCES

(1) (a) Vieira, L. M. M.; Kijjoa, A. Curr. Med. Chem. 2005, 12, 2413− 2446. (b) Masters, K.-S.; Bräse, S. Chem. Rev. 2012, 112, 3717−3776. (c) Winter, D. K.; Sloman, D. L.; Porco, J. A. Nat. Prod. Rep. 2013, 30, 382−391. (d) Wezeman, T.; Bräse, S.; Masters, K.-S. Nat. Prod. Rep. 2015, 32, 6−28. (2) (a) Han, A.-R.; Kim, J.-A.; Lantvit, D. D.; Kardono, L. B. S.; Riswan, S.; Chai, H.; Carcache de Blanco, E. J.; Farnsworth, N. R.; Swanson, S. M.; Kinghorn, A. D. J. Nat. Prod. 2009, 72, 2028−2031. (b) Niu, S.-L.; Li, Z.-L.; Ji, F.; Liu, G.-Y.; Zhao, N.; Liu, X.-Q.; Jing, Y.K.; Hua, H.-M. Phytochemistry 2012, 77, 280−286. (c) Sriyatep, T.; Siridechakorn, I.; Maneerat, W.; Pansanit, A.; Ritthiwigrom, T.; Andersen, R. J.; Laphookhieo, S. J. Nat. Prod. 2015, 78, 265−271. (3) (a) Chantarasriwong, O.; Batova, A.; Chavasiri, W.; Theodorakis, E. A. Chem. - Eur. J. 2010, 16, 9944−9962. (b) Ren, Y.; Matthew, S.; Lantvit, D. D.; Ninh, T. N.; Chai, H.; Fuchs, J. R.; Soejarto, D. D.; Carcache de Blanco, E. J.; Swanson, S. M.; Kinghorn, A. D. J. Nat. Prod. 2011, 74, 1117−1125. (4) (a) Xu, G.; Feng, C.; Zhou, Y.; Han, Q.-B.; Qiao, C.-F.; Huang, S.-X.; Chang, D. C.; Zhao, Q.-S.; Luo, K. Q.; Xu, H.-X. J. Agric. Food Chem. 2008, 56, 11144−11150. (b) Chien, S.-C.; Chyu, C.-F.; Chang, I.-S.; Chiu, H.-L.; Kuo, Y.-H. Tetrahedron Lett. 2008, 49, 5276−5278. (c) Huang, S.-X.; Feng, C.; Zhou, Y.; Xu, G.; Han, Q.-B.; Qiao, C.-F.; E


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