lable at ScienceDirect

Tetrahedron 72 (2016) 8400e8405

Contents lists avai

Tetrahedron

journal homepage: www.elsevier .com/locate/ tet

New picrotoxane terpenoids, austrobuxusin A-D, from the Australianendemic plant Austrobuxus swanii

Ozlem Demirkiran, Marc Campitelli, Chao Wang, Yunjiang Feng*

Eskitis Institute for Drug Discovery, School of Natural Sciences, Griffith University, Brisbane, Qld, 4111, Australia

a r t i c l e i n f o

Article history:Received 26 July 2016Received in revised form14 October 2016Accepted 24 October 2016Available online 27 October 2016

Keywords:Picrotoxane terpenoidsAustrobuxusPicrodendron

* Corresponding author.E-mail address: y.feng@griffith.edu.au (Y. Feng).

http://dx.doi.org/10.1016/j.tet.2016.10.0610040-4020/© 2016 Elsevier Ltd. All rights reserved.

a b s t r a c t

Four new picrotoxane terpenoids, austrobuxusin AeD (1e4), were isolated from the Australian endemicplant Austrobuxus swanii. Their structures were fully characterized by 1D- and 2D-NMR and MS data. Therelative configurations of compounds (1e4) were assigned by phase-sensitive ROESY experiment. Theabsolute configuration of austrobuxusin A (1) was determined by the comparison of experimental andDFT-calculated CD spectra. This is the first report of picrotoxane terpenoids from the Australian plantAustrobuxus swanii.

© 2016 Elsevier Ltd. All rights reserved.

1. Introduction

Picrotoxane and related natural products are a group of sec-ondary metabolites isolated from plant genera Picrodendron,1e5

Dendrobium,6e13 Baccaurea,14 and more recently Coriaria.15 Chem-ically, picrotoxanes possess structural features of nor-diterpenesand sesquiterpenes that are oxidised or rearranged at various po-sitions. Picrodendrins, one of the major picrotoxane terpenoids,also bear a unique carbon skeleton containing a spiro g-butyr-olactone.4,5 Biological activity investigation has shown that pic-rodendrin and related terpenoids inhibited the activity ofionotropic GABA receptors of mammals and insects,16,17 whichcontributed to the use of the plant P. baccatum as folk medicine tokill bugs and lice.18,19 Dendromonilisides A and C, picrotoxaneglycosides isolated from D. moniliforme, were also found to stimu-late the proliferation of B cells and inhibit the proliferation of T cellsin vitro.6 Recently, picrotoxane sesquiterpenes were reported toexhibit neurotoxicity,20 and antifungal activity against Colleto-trichum gloeosporioides.14

The plant genus Austrobuxus belongs to one of the endemic taxain Australia. Austrobuxus swanii is a rare subtropical rainforest treealso known as pink cherry.21 A literature search revealed it was apoorly investigated plant species with very little chemistry beingreported to date. The specimen examined in this study was

collected from Queensland, Australia. Chemical investigation of theMeOH/CH2Cl2 extract of the plant material resulted in four newpicrotoxane terpenoids, namely austrobuxusin AeD (1e4) (Fig. 1).We here report the isolation and structure elucidation of the fournew metabolites. We also applied a DFT-CD calculation to deter-mine the absolute configuration of austrobuxusin A (1).

2. Results and discussion

Ten grams of air-dried and ground leaves of A. swanii weresequentially extracted with n-hexane, CH2Cl2 and MeOH. Thecombined CH2Cl2/MeOH extract was initially chromatographedthrough polyamide gel to eliminate tannin-like compounds. Theresulting MeOH eluent was subjected to several rounds of reverse-phase C18 chromatography to afford four new picrotoxane terpenes(Fig. 1.), namely austrobuxusin A (1, 3.5 mg, 0.035% dry wt), aus-trobuxusin B (2, 16 mg, 0.16% dry wt), austrobuxusin C (3, 6.5 mg,0.065% dry wt), and austrobuxusin D (4, 6.5 mg, 0.065% dry wt).

Austrobuxusin A (1) was obtained as an optically active whitepowder with an [a] D

20 value of þ13.4 (MeOH, c 0.06). Its molecularformula of C26H28O12 was determined by HRESIMS (m/z 555.1478,calcd for C26H28O12Na [MþNa]þ 555.1473), with thirteen degrees ofunsaturation. IR absorptions at 3421 (br) and 1765 cm�1 indicatedthe presence of hydroxyl and carbonyl functionalities. Detailedanalysis of its 1H and 13C NMR spectral data (Table 1) suggested thataustrobuxusin A had similar structural features to those of pic-rodendrin F.4 Major differences in austrobuxusin A included thereplacement of an isopropylmoiety by an isopropenyl functionality,

Fig. 1. Chemical structures of austrobuxusins A-D (1e4) and picrodendrin F.

O. Demirkiran et al. / Tetrahedron 72 (2016) 8400e8405 8401

the presence of a galloyl group, and the removal of a hydroxyl groupat C-4. Twenty six carbon signals were observed in the 13C NMRspectrum, including fourteen protonated carbons by HSQC and tenquaternary carbons. Of the ten quaternary carbons, three werecarbonyl carbons (dC 174.9, 174.4 and 165.2), four sp2 carbons (dC145.4, 142.0, 138.7 and 119.1), and three aliphatic sp3 carbons (dC89.8, 75.9, and 53.7). Detailed analysis of COSY, HSQC and HMBCcorrelations confirmed that 1 had the same ring skeleton as that ofpicrodendrin F,4 including an epoxy ring and a spiro g-butyrolactone.

The presence of an isopropenyl functionality in the moleculewas based on the HMBC correlations from the sp2 vinyl protons (dH4.79 and 4.61) to the methyl carbon (dC 22.7), and from the methylprotons (dH 1.81) to the two sp2 carbons (dC 142.1 and 110.0). Theisopropenyl group was assigned at the C-4 position based on theHMBC correlations (Fig. 2) from the vinyl (dH 4.79 and 4.61, H-9)and methyl (dH 1.81, H-10) protons to the C-4 carbon (dC 48.7). Theabsence of a hydroxyl group at the C-4 position was evident by the

Table 1NMR data for austrobuxusin A (1) in DMSO-d6.

No. 1H, mult. (J in Hz)a 13C, typeb

1 e 53.7, C2 4.04, brs 72.0, CH3 4.72, d (4.5) 82.4, CH4 3.20, brs 48.7, CH5 2.99, d (4.5) 49.0, CH6 e 75.9, C7 1.03, s 24.0, CH3

8 e 142.0, C9a 4.61, brs 110.0, CH2

9b 4.79, brs10 1.81, s 22.7, CH3

11 3.63, d (2.4) 62.6, CH12 3.17, d (2.4) 60.4, CH13 e 89.8, C14a 1.69, dd (11.5, 5.5) 30.8, CH2

14b 3.57, dd (13.5, 11.5)15 e 174.4, C16 3.10, m 44.7, CH17 e 174.9, C18 5.18, m 69.8, CH19 1.36, d (6.5) 16.9, CH3

20 e 165.2, C10 e 119.120 6.91, s 108.530 e 145.540 e 138.750 e 145.560 6.91, s 108.5

a 1H NMR spectrum was recorded at 600 MHz.b 13C NMR spectrum was recorded at 150 MHz.

presence of a methine proton (dH 3.20), and the COSY correlationsfrom the methine proton (dH 3.20) to H-3 and H-5 (dH 4.72 and2.99).

The presence of a galloyl ester functionality at C-18 was basedon further analysis of 1D and 2D NMR data. 13C NMR data revealedthe presence of four aromatic carbons (dC 145.5, 138.7, 119.1 and108.8). HSQC correlation data indicated that the two aromaticprotons (dH 6.91, s, 2H) were attached to the same aromatic carbon(dC 108.8), suggesting a symmetrically substituted phenyl ring. TheHMBC correlations from the aromatic proton (dH 6.91) to thecarbonyl carbon (dC 165.2) and the aromatic carbons (dC 145.5 and138.7) suggested a galloyl moiety. The assignment was furtherconfirmed by the observation of a fragment ion atm/z 153 in ESIMSspectrum. Further HMBC correlation from the H-18 proton signal(dH 5.18) to the galloyl carbonyl carbon (dC 165.2) enabled theassignment of an ester bond between the galloyl moiety and hy-droxyl group at C-18. Therefore, the gross structure of austro-buxusin A was assigned as 1.

HMBC ROESY

e e

e H3, H7, H9aC1, C4, C5, C15 H2, H4, H9ae H3, H5, H10C1, C3, C4, C6, C11, C15 H4, H10, H11e e

C1, C2, C13 H2e e

C4, C10 H2, H3, H9bC4, C10 H9a, H10C4, C8, C9 H4, H5, H9bC1, C6, C13 H5, H12C1, C6, C13, C14 H11, H14ae e

C1, C12, C13, C18 H12, H14b, H19C1, C12, C13, C17, C18 H14a, H16e e

C17, C18, C19 H14b, H18e e

C14, C17, C19, C20 H16, H19C16, C18 H14a, H18e e

e e

C10 , C30 , C40 , C60 , C20 e

e e

e e

e e

C10 , C20 , C40 , C50 , C20 e

O

O

O

O

HO

OHO

O H

O

HO

HO OH1

23

4

56

7

8

9

10

1112

13

14

15

16

1718

19

Fig. 2. Key HMBC (/) and ROESY ( ) correlations for 1.

O. Demirkiran et al. / Tetrahedron 72 (2016) 8400e84058402

The relative configuration of 1 was determined by the detailedanalysis of ROESY correlation data (Table 1) depicted in a 3D modelof the lowest energy conformer of the compound (Fig. 2). Theconformer was obtained by the molecular mechanics energyminimization and conformational searches using MMFFs. Impor-tantly, the ROESY correlations were observed (Fig. 2) fromH-2 to H-3, CH3-7 and H-9a, indicating H-2, H-3, the methyl group at C-1 andthe isopropenyl group at C-4 were on the same side of the bicyclo[4,3,0]nonane ring system. Further ROESY correlations wereobserved fromH-14a to H-12 and CH3-19, suggesting that the bondbetween C-13 and C-14, H-12, and the 2-oxyethyl side chain at C-16were on the other side of the bicycle system. A key ROESY corre-lation between H-5 and H-11 suggested that the bicyclo[4,3,0]

Fig. 3. The experimental and calculated EC

nonane ring system was cis-fused. These observations indicatedthat all the chiral carbons in the ring system had the same relativeconfiguration as those of picodendrin F. However, the relativeconfiguration of C-18 in the side chain cannot be unambiguouslyassigned by the ROESY correlation data.

Ideally the absolute configuration of compound 1 would beobtained through X-ray structural analysis. However, attempts togrow crystals suitable for X-ray diffraction studies for the fourcompounds were unsuccessful, we thus explored alternativemethods for structure verification. Owing to the galloyl function-ality in the molecule, we were able to experimentally acquire anelectronic circular dichroism (ECD) spectrum for austrobuxusin A(1) and compared the spectrum with those predicted using time-

D overlay of 1 and its stereoisomers.

O. Demirkiran et al. / Tetrahedron 72 (2016) 8400e8405 8403

dependent density functional theory (TDDFT). Four stereoisomerswere conceivable: twowith an 18R absolute configuration (Fig. 3,1aand its enantiomer) and two with an 18S absolute configuration(Fig. 3, 1b and its enantiomer).

For ECD calculation, all structures were subjected to geometryoptimization in MacroModel22 using MMFFs. Conformationalsearches were performed on each structure using a mixed MCMM/Low-Mode search. All conformers identified by MacroModel weresubjected to further gas-phase geometry optimization in Jaguar23

using the B3LYP functional and 6-31G(d,p) basis set. TheoreticalECD spectra were calculated using the GIAO method from single-point BHandLYP/def2-TZVP calculations including the COSMO sol-vation model (MeOH). The final ECD curves for each stereoisomerwere generated using a Boltzmann-weighted average of all con-formers (Fig. 3).

The comparison of the experimental and calculated ECD spectra(Fig. 3) showed that the calculated ECD spectrum for both C18-Renantiomers did not match the experimental spectrum. Theexperimental ECD curve of 1, however, matched well with C18eSenantiomer 1b. This result, in combination with the ROESY exper-imental data, confirmed that austrobuxusin A (1) had the sameabsolute configuration in the ring system as that of picrodendrin F,but an opposite configuration at the C-18 position. The absoluteconfiguration of austrobuxusin A (1) was therefore determined tobe 1R,2S,3S,4R,5R,6R,11S,12R,13S,16S,18S.

Austrobuxusin B (2) was obtained as an optically active whitepowder with an [a] D

20 value of þ34.0 (MeOH, c 0.05). Its molecularformula, C20H26O9, was deduced on the basis of HRESIMS mea-surement (m/z 433.1470, calcd for C20H26O9Na [MþNa]þ 433.1469),with eight degrees of unsaturation. IR absorptions at 3330 (br) and1770 cm�1 indicated the presence of hydroxyl and carbonyl func-tionalities. Detailed analysis of its 1H and 13C NMR spectral data(Table 2) suggested that austrobuxusin B (2) had a similar structuralfeatures to those of austrobuxusin A (1). Major differences includedthe replacement of the galloyl group in 1 by a methoxy group in 2,and the absence of a methine functionality in 2. The presence of amethoxy group at C-18 was supported by the HMBC correlation

Table 21H and13C NMR data for austrobuxusins B, C and D (2e4).

Position 2 3

dHa mult. (J in Hz) dC

b dHa mult. (J in

1 e 51.3 e

2 4.07, brs 72.0 4.11, brs3 4.70, brd (4.0) 82.7 4.75, brd (5.04 3.17c 48.8 3.20, dd (5.0,5 2.96, d (3.5) 49.3 3.0, d (5.0)6 e 75.9 e

7 1.14, s 23.5 1.15, s8 e 142.1 e

9a 4.57, brs 110.0 4.62 brs9b 4.80, brs 4.83 brs10 1.81, s 22.6 1.84, s11 3.62, d (2.4) 61.2 3.64, d (2.5)12 3.80, d (2.4) 60.7 3.68, d (2.5)13 90.9 e

14a 1.85, d (12.0) 34.9 2.11, dd (12.514b 3.76, d (12.0) 3.55, dd (12.515 e 174.9 e

16 e 78.1 3.10, ddd (1217 e 175.6 e

18 3.42, q (5.5) 76.6 3.60, m19 1.06, d (5.5) 13.0 1.14, d (5.3)20 3.18, s 56.6 3.18, s

a 1H NMR spectra were recorded at 600 MHz.b 13C NMR spectra were recorded at 150 MHz.c Signals overlapping.

from a methyl singlet (dH 3.18) to C-18 (dC 76.6). A hydroxyl func-tionality was assigned at C-16, replacing a methine functionality in1 (dH 3.10, dC 44.7), based on the presence of an oxygenated carbon(dC 78.1 in 2). The assignment was confirmed by the HMBC corre-lations fromH-14 (dH 3.76) and H-18 (dH 3.42) to the carbon. SimilarROESY correlations were observed for compound 2, suggesting that2 had the same relative configuration as that of 1. The structure ofaustrobuxusin B was therefore determined as 2.

Austrobuxusin C (3) was obtained as an optically active whitepowder with an [a] D

20 value of þ17.6 (MeOH, c 0.125). Its molecularformula was established as C20H26O8 by HRESIMS (m/z 395.1687,calcd. for C20H27O8 [MþH]þ 395.1700), 16 mass units less than thatof austrobuxusin B. The comparison of the 1H and 13C NMR spectraindicated that compound 3 had a similar structure to that of 2. Theonly difference was the presence of a methine signal (dH 3.10 and dC46.3) in 3 instead of an oxygenated quaternary carbon (dC 78.1) in 2.COSY correlations were observed from the methine proton to H-14(dH 3.55 and 2.11) and H-18 (dH 3.60), indicating a reduction of thehydroxyl functionality at C-16. HMBC correlations from themethine proton to the C-13 quaternary carbon (dC 91.2) and C-19methyl carbon (dC 18.2) confirmed the assignment. The two largecoupling constants of H-16 (J ¼ 12.5 and 9.0 Hz) indicated that thedihedral angles between H-16 and H-14a/H-18 are ca. ~0�, howeverthe small coupling constant of H-16 (J ¼ 3.5 Hz) was indicative for aca 160� orientation between H-16 and H-14b. This relative config-urationwas further confirmed by the ROESY correlations fromH-16to H-18 and H-14b. Similar ROESY correlations were also observed,indicating that compound 3 had the same relative configuration asthat of 1 and 2.

Austrobuxusin D (4) was obtained as white powder with an [a]D20 value of �15.0 (MeOH, c 0.09). Its molecular formula wasestablished as C19H20O7 by HRESIMS (m/z 383.1084, calcd. forC19H20O7Na [MþNa]þ 383.1101). Nineteen carbon signals wereobserved in the 13C NMR spectra of 4. HSQC correlation data indi-cated twelve protonated carbons including eight methines, onemethylene, and three methyls. The formation of a tetrahydrofuranring between C-2 and C-14 was determined by the two distinct

4

Hz) dCb dH

a mult. (J in Hz) dCb

51.9 e 54.872.9 4.34, d (3.5) 85.9

) 83.5 5.06, dd (4.2, 3.5) 81.55.0) 49.5 3.42, brs 47.8

50.1 3.14, d (3.5) 49.676.7 e 74.824.3 0.93, s 22.0142.8 e 140.6111.0 4.80, brs 112.3

4.84, brs23.4 1.83, s 23.360.8 3.82, d (2.0) 64.061.9 3.76, d (2.0) 56.991.2 e 100.4

, 9.0) 29.1 4.97, s 77.9, 3.5)

175.7 e 175.1.5, 9.0, 3.5) 46.3 e 128.9

176.3 e 167.374.6 6.94, q (5.7) 144.018.2 1.96, d (5.7) 16.656.7 e e

O. Demirkiran et al. / Tetrahedron 72 (2016) 8400e84058404

HMBC correlations fromH-14 (dH 4.97) to C-2 (dC 85.9), and fromH-2 (dH 4.34) to C-14 (dC 77.9). A downfield shift of the spiro C-13 (DdC~10) suggested that the spiro carbonwas in a different environmentas that in compounds 1e3, hence confirming the assignment. Afurther CH3eCH]functionality was elucidated by the COSY corre-lations between a methyl doublet (dH 1.96) and a vinyl eCH quartet(dH 6.94). Further HMBC correlations from the methyl doublet tothe quaternary carbon (dC 128.9), and from the olefinic proton (dH6.94) to C-14 (dC 77.9) and C-16 (dC 128.9) suggested that theCH3eCH]fragment was attached at the C-16 position. The relativeconfiguration of 4 was determined as the same as those of com-pounds 1e3 based on ROESY correlation data.

The absolute configurations of compounds 2e4 were proposedto be the same as that of 1 based on their common biogenesis. Thisis the first report of picrotoxane terpenoids from the Australianendemic plant A. swanii.

3. Experimental section

3.1. General experimental procedures

Optical rotations were recorded on a Jasco P-1020 polarimeter.IR spectra were recorded on a Bruker Tensor 27 spectrometer andan Agilent 8453 UV/vis spectrophotometer. CD spectra werecollected on a Jasco 715 spectropolarimeter. LRESIMS were recor-ded on aWaters ZQmass spectrometer. HRESIMS were recorded ona Bruker Daltronics Apex III 4.7e Fourier-transform mass spec-trometer. NMR spectra were recorded at 30 �C on a Varian 600MHzUnity INOVA spectrometer. The spectrometer was equipped with atriple resonance cold probe. The 1H and 13C chemical shifts werereferenced to the solvent peak for DMSO-d6 at dH 2.50 and dC 39.5.An Edwards Instrument Company bio-line orbital shaker was usedfor large-scale biota extraction. AWaters 600 pump equipped witha Waters 996 PDA detector and a Waters 717 autosampler wereused for HPLC. A ThermoElectron C18 Betasil 5 mm 143 Å column(21.2 mm � 150 mm) was used for semi-preparative HPLCseparations. Alltech Davisil 40e60 mm 60 Å C18 bonded silica wasused for pre-adsorption work. Machery Nagel Polyamide CC6(0.05e0.016 mm) was used for tannin/polyphenolic removal. Allsolvents used for chromatography, IR, CD, [a]D and MS were Lab-Scan HPLC grade, and the H2O was Millipore Milli-Q PF filtered.

3.2. Plant material

The leaves of Austrobuxus swanii were collected fromQueensland, Australia, in November 1993. The plant was identifiedby Dr P. Foster from Queensland Herbarium. A voucher sample(0323059804022895) has been lodged at the Queensland Herbar-ium, Brisbane, Australia.

3.3. Extraction and isolation

The air dried and ground leaves of Austrobuxus swanii (10 g)was transferred to a conical flask (1 L), n-hexane (250 mL) wasadded and the flask was shaken at 200 rpm for 2 h. The n-hexaneextract was filtered under gravity then discarded. DCM (250 mL)was added to the de-fatted biota in the conical flask and shakenat 200 rpm for 2 h. The resulting extract was filtered undergravity, and set aside. MeOH (250 mL) was added and the MeOH/biota mixture was shaken for a further 2 h at 200 rpm. Followinggravity filtration the biota was extracted with another volume ofMeOH (250 mL), while being shaken at 200 rpm for 16 h. AllDCM/MeOH extracts were combined and dried down underreduced pressure to yield a dark brown solid (2.5 g). This ma-terial was re-suspended in MeOH (150 mL) and loaded onto a

MeOH conditioned polyamide gel (30 g) in a sintered glass col-umn and washed with MeOH (300 mL). The resulting extract(1.8 g) was pre-adsorbed onto C18-bonded silica, then packed intoa stainless steel cartridge (10 � 30 mm) that was subsequentlyattached to a C18 semi-preparative HPLC column. A lineargradient from H2O (0.1% TFA) to MeOH (0.1% TFA) at a flow rate of9 mL/min over 60 min was run and 1 min fractions werecollected. Fractions 30 and 36 contained pure compounds 1(3.5 mg, 0.035% dry wt) and 4 (6.5 mg, 0.065% dry wt), respec-tively. Fraction 33 was further purified using CN bonded pre-parative thin layer chromatography. A H2O:MeOH (1:1) solventsystem was used to yield compound 3 (6.5 mg, 0.065% dry wt).Fractions 41e42 were further purified by C18 semi-preparativeHPLC column. A linear gradient from 10% MeOH (0.1% TFA) to25% MeOH (0.1% TFA) for the first 10 min and from 25% MeOH(0.1% TFA) to 55% MeOH (0.1% TFA) for 45 min at a flow rate of9 mL/min was used and yielded compound 2 (16 mg, 0.16% drywt).

Austrobuxusin A (1) was isolated as awhite powder; [a] D20þ13.4(MeOH, c 0.06); IR nmax (KBr) 3421 (br), 1765, 1224, 998 cm�1; 1Hand 13C NMR data (DMSO-d6) see Table 1; (þ)-HRESIMS m/z555.1478 (C26H28O12Na [MþNa]þ calcd 555.1473).

Austrobuxusin B (2) was isolated as awhite powder; [a] D20þ34.0(MeOH, c 0.05); IR nmax (KBr) 3330 (br), 1770, 1024, 992, 904 cm�1;1H and 13C NMR data (DMSO-d6) see Table 2; (þ)-HRESIMS m/z433.1470 (C20H26O9Na [MþNa]þ calcd 433.1469).

Austrobuxusin C (3) was isolated as awhite powder; [a] D20þ17.6(MeOH, c 0.125); IR nmax (KBr) 3400 (br), 1762, 1617, 1343, 1214,1081 cm�1; 1H and 13C NMR data (DMSO-d6) see Table 2;(þ)-HRESIMS m/z 395.1687 (C20H27O8 [MþH]þ calcd 395.1700).

Austrobuxusin D (4) was isolated as a white powder; [a] D20 -15.0(MeOH, c 0.09); IR nmax (KBr) 3409 (br), 2990, 1760, 1680, 1245,1018, 992 cm�1; 1H and 13C NMR data (DMSO-d6) see Table 2;(þ)-HRESIMS m/z 383.1084 (C19H20O7Na [MþNa]þ calcd 383.1101).

3.4. ECD calculation for 1

All structures were subjected to geometry optimization inMacroModel using MMFFs with H2O solvation. Conformationalsearches were performed on each structure using a mixed MCMM/Low-Mode search with 1000 steps per rotatable bond and an en-ergy window of 21 kJ mol�1 for retention of conformers. All con-formers identified by MacroModel were subjected to further gas-phase geometry optimization in Jaguar using the B3LYP func-tional and 6-31G(d,p) basis set. A fine integration grid with accurateSCF convergence criteriawas employed and all geometry optimizedstructures were characterized as true minima by the absence ofimaginary vibrational frequencies at the stationary point. Theo-retical ECD spectra were calculated using the GIAO method asimplemented in ORCA (v 3.0.3) using single-point BHandLYP/def2-TZVP calculations employing the COSMO implicit solvation model(MeOH) with the RIJCOSX approximation. The theoretical ECDspectrum was the Boltzmann-weighted average calculated for allconformers using SpecDis 1.62 with a wavelength correction of40 nm by comparison of the calculated and experimental UVspectra.

Acknowledgements

The authors acknowledge the Australian Research Council (ARC)for support towards NMR andMS equipment (Grant LP120200339).We thank H. Vu from Griffith University for acquiring the HRESIMSmeasurements. We also thank Dr P. Foster from Queensland Her-barium for plant collection and identification.

O. Demirkiran et al. / Tetrahedron 72 (2016) 8400e8405 8405

Appendix A. Supplementary data

Supplementary data (1D- and 2D-NMR spectra of compounds1e4) associated with this article can be found at http://dx.doi.org/10.1016/j.tet.2016.10.061.

References

1. Suzuki Y, Koike K, Ohmoto T. Phytochemistry. 1992;31:2059.2. Nagahisa M, Koike K, Narita M, Ohmoto T. Tetrahedron. 1994;50:10859.3. Koike K, Suzuki Y, Ohmoto T. Phytochemistry. 1994;35:701.4. Koike K, Ohmoto T, Kawai T, Sato T. Phytochemistry. 1991;30:3353.5. Suzuki Y, Koike K, Nagahisa M, Nikaido T. Tetrahedron. 2003;59:6019.6. Zhao C, Liu Q, Halaweish F, Shao B, Ye Y, Zhao W. J Nat Prod. 2003;66:1140.7. Qin X, Qu Y, Ning L, Liu J, Fan S. J Asian Nat Prod Res. 2011;13:1047.8. Zhang X, Tu F, Yu H, Wang N, Wang Z, Yao X. Chem Pharm Bull. 2008;56:854.

9. Zhang X, Liu H, Gao H, et al. Helv Chim Acta. 2007;90:2386.10. Ying S, Zhang D, Guo S. J Asian Nat Prod Res. 2004;6:311.11. Zhao W, Ye Q, Dai J, Martin M, Zhu J. Planta Med. 2003;69:1136.12. Zhao C, Liu Q, Halaweish F, Shao B, Ye Y, Zhao W. J Nat Prod. 2003;66:1140.13. Ye Q, Qin G, Zhao W. Phytochemistry. 2002;61:885.14. Pan Z, Ning D, Huang S, Wu Y, Ding T, Luo L. Nat Prod Res. 2015;29:1323.15. Shen Y, Li S, Li R, et al. Org Lett. 2004;6:1593.16. Ozoe Y, Akamatsu M, Higata T, et al. Bioorg Med Chem. 1998;6:481.17. Schmidt TJ, Gurrah M, Ozoe Y. Bioorg Med Chem. 2004;12:4159.18. Scattelle DB. Adv Insect Physiol. 1990;22:1.19. Hayden WJ, Gillis WT, Stone DE, Broome CR, Webster GL. J Arnold Arbor.

1984;65:105.20. Larsen L, Joyce NI, Sansom CE, Cooney JM, Jensen DJ, Perry NB. J Nat Prod.

2015;78:1363.21. Floyd AG. Rainforest Trees of Mainland South-eastern Australia. Inkata Press;

2008:286.22. Suite. MacroModel, Version 9.9, Schr€Odinger. New York, NY 2012: LLC; 2012.23. Suite. Jaguar, Version 7.9, Schr€Odinger. New York, NY 2012: LLC; 2012.

本文献由“学霸图书馆-文献云下载”收集自网络，仅供学习交流使用。

学霸图书馆（www.xuebalib.com）是一个“整合众多图书馆数据库资源，

提供一站式文献检索和下载服务”的24 小时在线不限IP

图书馆。

图书馆致力于便利、促进学习与科研，提供最强文献下载服务。

图书馆导航：

图书馆首页 文献云下载 图书馆入口 外文数据库大全 疑难文献辅助工具