Lignans and sesquiterpenoids from the stems of Schisandra bicolor var.tuberculata

Shui?Mei Zhang,Kun Hu,Xiao?Nian Li,Han?Dong Sun and Pema?Tenzin Puno

1 State Key Laboratory of Phytochemistry and Plant Resources in West China,Yunnan Key Laboratory of Natural Medicinal Chemistry,Kunming Institute of Botany,Chinese Academy of Sciences,Kunming 650201,People’s Republic of China

Abstract A pair of new tetrahydrofuran lignan enantiomers,(±)?schibiculatin A [(±)?1],a new enedione lignan,schibiculatin B(2),two new cadinane?type sesquiterpenoids,schibiculatins C (3) and D (4),along with two known seco?cadinane?type sesquiterpenoids (5 and 6) and seven known miscellaneous lignans (7—13) were isolated from the stems of Schisandra bicolor var.tuberculata.The structures of 1—4 were elucidated by comprehensive analysis of their spectro?scopic data,quantum chemical calculations,as well as single?crystal X?ray diffraction.A few isolated compounds were tested for their protective activities against corticosterone?induced apoptosis in PC12 cells.Among them,compounds 5 and 6 showed moderate activities.

Keywords: Schisandra bicolor var.tuberculata,Cadinane?type sesquiterpenoids,Lignans,Quantum chemical calculation

1 Introduction

The family Schisandraceae,including generaSchisandraandKadsura,is a medicinally important plant taxon widely distributed in Southeastern Asia and Southeastern America.Previous phytochemical investigations on Schisandraceae species have led to the discovery of an array of structurally diverse natural products,including lignans [1,2],triterpenoids [3–6],sesquiterpenoids [7,8],etc.These compounds were found to exhibit various beneficial biological functions,including anti-HIV activity[9],hepatoprotective activity [1,10],anti-hepatitis activity [11],neuroprotective activity [6,12],inhibitory activity on proliferation of rheumatoid arthritis-fibroblastoid synovial cells [13],and so on.

Schisandra bicolorvar.tuberculatais a climbing plant widely distributed in Guizhou,Hunan,and Jiangxi Provinces of China.Several studies have been undertaken to explore the chemical constituents and their bioactivities ofS.bicolorvar.tuberculataand its original variant,S.bicolor.For example,two new 3,4-seco-cycloartane triterpenoids from the stems ofS.bicolorwere reported by Qin et al.[14];seven described cadinane-type sesquiterpenoids were isolated by Huang et al.from the stems ofS.bicolor,and most of them were considered as chemotaxonomic markers of this species [7];tetrahydrofuran-type[15],dibenzylbutane-type [16],and dibenzocyclooctanetype lignans have also been obtained fromS.bicolorvar.tuberculataorS.bicolor,and some of them were found to exhibit statistically significant neuroprotective activities [12].Considering thatS.bicolorvar.tuberculatahas rarely been phytochemically investigated,in the current research,S.var.tuberculatacollected from Guizhou Province,China was subjected to phytochemical study to search for structurally and biologically fascinating molecules.As a result,a pair of new tetrahydrofuran lignan enantiomers,(±)-schibiculatin A [(±)-1],a new enedione lignan,schibiculatin B (2),two new cadinane-type sesquiterpenoids,schibiculatins C (3) and D (4),along with two knownseco-cadinane-type sesquiterpenoids (5 and 6) and seven known miscellaneous lignans (7–13)were obtained (Fig.1).The structures of new compounds were elucidated by comprehensive analysis of their spectroscopic data,quantum chemical calculations,as well as single-crystal X-ray diffraction.This paper deals with the isolation,structural characterization,and bioactivity evaluation of these compounds.

Fig.1 Chemical structures of compounds 1—13

2 Results and discussion

Compound 1 (schibiculatin A) was obtained as colorless crystals.It was assigned the molecular formula of C25H34O9according to the ion peak atm/z501.2102([M+Na]+,calcd for 501.2095) in the HR-ESI-MS analysis and its13C NMR spectrum,suggesting nine degrees of unsaturation.The IR spectrum showed characteristic absorption peaks for hydroxyl group (3436 cm?1) and aromatic moieties (1630,1594,1507,1463 cm?1).The1H NMR spectrum showed two methyl groups (δH0.94 and 1.34);two methine protons (δH2.44 and 4.81);four aromatic protons [δH6.75 (2H),6.83 (2H)];and seven methoxy groups [δH3.23 (3H),3.77 (6H),3.86 (12H)].Besides,the13C and DEPT NMR spectra showed signals for two methyls (δC8.8 and 19.4),two methines (δC50.4 and 89.0),two non-protonated carbons (δC83.6 and 113.4),as well as eight resonances for aromatic carbons (δC105.8,107.2,134.1,138.7,138.9,139.0,154.0,and 154.5).The above information (Table 1),in combination with the HMBC spectrum,suggested that compound 1 is a tetrahydrofuran lignan with two 3,4,5-trimethoxyphenyl groups.A comprehensive analysis of the1H–1H COSY and HMBC spectra (Fig.2)indicated that the structure of 1 is closely related to that of kalongirin A [17],and the main difference was that the latter possessed only one symmetric trimethoxyphenyl ring.The HMBC correlations from H-7′ to C-7 and C-8,from 7-OCH3(δH3.23) to C-7,from H3-9 to C-7 and C-8,in combination with the H-7′/H-8′/H-9′spin system revealed by the1H–1H COSY spectrum,confirmed the tetrahydrofuran moiety in 1.The HMBC correlations from six methoxy groups to C-3,C-4,C-5,C-3′,C-4′,and C-5,respectively,along with the HMBC correlations from H-7′ to C-2′ and C-6′,confirmed the existence of two 3,4,5-trimethoxyphenyl groups and their attachment to C-7 and C-7′,respectively.The key correlations between H-9 and H-8′,H-9 and CH3O-7,H-7′ and H-9′ in the ROESY spectrum (Fig.3),along with the3JH-7′/H-8′(10.2 Hz) revealed the relative configuration of 1 to be 7S*,8S*,7′S*,and 8′R*.Thus,1 was determined as (7S*,8S*,7′S*,8′R*)-8-hydroxy-3,4,5,7,3′,4′,5′-heptamethoxy-7,7′-epoxylignan.Crystals of 1 were obtained and subjected to X-ray diffraction analysis (Fig.4),which not only proved the established structure,but also revealed that it was a racemic mixture.Chiral resolution of 1 afforded (+)-1 and (?)-1,and their absolute configurations were determined through TDDFT ECD calculation.According to the computational result (Fig.5),the absolute configuration of (+)-1 was determined as 7R,8R,7′R,and 8′S,and that of (?)-1 was determined as 7S,8S,7′S,and 8′R.

Table 1 1H and 13C NMR spectroscopic data for compounds 1 and 2 (δ in ppm,J in Hz)

Fig.2 1H—1H COSY (red lines) and selected HMBC (blue arrows H→C) of compounds 1—4

Fig.3 Key ROESY correlations (blue dashed double?headed arrow) of (±)?1,3,and 4

Fig.4 X?ray structure of (±)?1

Fig.5 Experimental ECD spectrum of (?)?1 (black);calculated ECD spectrum of (7S,8S,7′S,8′R)?1 (shift=1 nm,red)

Compound 2 (schibiculatin B) was obtained as a colorless oil.Its molecular formula was assigned as C23H26O7according to the sodium adduct ion atm/z437.1566 ([M+Na]+,calcd for 437.1571) in the(+)-HR-ESI-MS spectrum,indicating eleven degrees of unsaturation.The IR spectrum showed characteristic absorption peaks for aromatic moieties (1649,1584,1511,1463,and 1416 cm?1),and carboxyl groups (1737 and 1722 cm?1).Its1H NMR spectrum(Table 1) showed two methyl groups [δH2.17 (6H)]and five aromatic protons [δH6.71 (2H),6.74,6.93,7.18],and five methoxy groups (δH3.77,3.78 (6H),3.87,3.90).The13C NMR,DEPT,and HSQC spectra exhibited 23 carbons (Table 1),including two methyl groups (δC17.3 and 17.5),fourteen olefinic carbons [δC106.6 (2C),109.5,110.2,124.9,130.4,132.3,138.0,139.4,142.3,148.9,152.7 (2C),153.3],two carboxyl groups (δC197.7 and 197.9),and five methoxy groups [δC55.8,56.0,56.1 (2C),60.9].The1H and13C NMR spectra of 2 were similar to those ofthreo-2-methyl-3-oxo-1-(3′,4′,5′-trimethoxyphenyl)butyl-3″,4″-dimethoxybenzoate [18],and the main difference was the substitution patterns of two aromatic rings.Careful analysis of the above information(Table 1) suggested the presence of a 3,4,5-trimethoxyphenyl group and a 3,4-dimethoxyphenyl group in 2.The HMBC correlations from H-2,H-6 to C-7 (δC197.9),and from H-2′,H-6′ to C-7′ (δC197.7) assigned the locations of two carboxyl groups.In addition,the HMBC correlations from H-9 to C-7 and C-8′,from H-9′ to C-8 and C-7′ established the C-8/C-8′ tetrasubstituted double bond.However,the geometry of C-8/C-8′ double bond can’t be determined through ROESY correlations due to the overlap of H-9 and H-9′ in1H NMR spectrum.Thus,two geometric isomers of 2,8E-2(2a) and 8Z-2 (2b) were subjected to quantum chemical calculation of NMR chemical shifts.According to the computational results,including R2,MAE,CMAE [19],and DP4+ probability [20] (Table 3),the C-8/C-8′ double bond was determined to adoptEgeometry.Thus,2 was determined as (E)-1-(3′,4′,5′-trimethoxyphenyl)-4-(3″,4″-dimethoxyphenyl)-2,3-dimethylbut-2-ene-1,4-dione.

Compound 3 (schibiculatin C) was obtained as a colorless oil.Its molecular formula was established as C15H24O3by analysis of its (+)-HR-ESI-MS data([M+Na]+m/z275.1621,calcd for 275.1618),suggesting four degrees of unsaturation.The IR spectrum of 3 showed a characteristic absorption peak (3428 cm?1) for a hydroxy group.The1H spectrum showed four singlet methyl groups (δH1.17,1.32,1.36,and 1.64);two methine protons (δH2.76 and 4.44),two hydroxyl protons (δH5.72 and 6.37).The13C NMR and DEPT spectra,in combination with the HSQC spectrum showed fifteen carbon resonances,including four methyls (δC22.2,24.5,28.4,and 29.4),four methylenes (δC21.3,22.2,32.8,and 33.8),two methines (δC41.5 and 76.4),and five non-protonated carbons (including three oxygenated methines atδC71.8,73.1,and 74.1;two olefinic carbons atδC135.6 and 140.2).The aforementioned NMR data of 3 (Table 2) indicated it is a cadinane-type sesquiterpene structurally similar to(4R,5R,10R)-10-methoxymuurol-1(6)-ene-4,5-diol [21].The1H–1H COSY spectrum of 3 revealed the presence of three spin systems (Fig.2) through H-2a (δH2.53)/H-3b (δH1.97),HO-5 (δH6.37)/H-5 (δH4.44),and H-7 (δH2.76)/H-8b (δH1.52)/H-9a (δH1.76) correlations.In the HMBC spectrum of 3 (Fig.2),correlations from CH3-13(δH1.17) to C-7 (δC41.5),C-11 (δC74.1),and C-12 (δC28.4);from CH3-14 (δH1.36) to C-1 (δC135.6),C-9 (δC32.8),and C-10 (δC73.1);from CH3-15 (δH1.64) to C-3(δC33.8),C-4 (δC71.8),and C-5 (δC76.4) indicated that two methyls and one isopropyl group were attached to C-4,C-10,and C-7,respectively.Besides,the HMBC correlations (Fig.2) from H-3a,H-3b,H-5,H-7,H-9a and H-9b to C-1;and from H-2,H-8,andHO-5 to C-6(δC140.2),suggested the presence of the C-1/C-6 double bond.The remaining one degree of unsaturation implied the existence of an epoxy ring,which was deduced to form between C-10 and C-11 according to molecular modeling.Assigning H-5 asα-oriented,the H-7/H-5α,CH3-13/H-5α,CH3-15/H-5αcorrelations (Fig.3) in the ROESY spectrum indicated that both CH3-15 and the epoxy ring adoptα-orientation.Subsequently,quantum chemical calculation of NMR chemical shifts succeeded in confirming the established the structure of 3 (Table 3).However,TDDFT calculation failed to produce the experimental ECD curve of 3,despite that several independent methods have been tried.Thus,the absolute configuration of 3 was left undermined.The structure of 3 was established as 10,11-epoxy-cadin-1(6)-ene-4,5-diol.

Compound 4 (schibiculatin D) was isolated as a colorless oil.Its molecular formula was assigned as C15H24O4according to the sodium adduct ion peak atm/z291.1566([M+Na]+,calcd 291.1567) in the (+)-HR-ESI-MS spectrum,indicating four degrees of unsaturation.The IR spectrum showed characteristic absorption peaks for hydroxyl group (3427 cm?1),double bond (1462,1611 cm?1),and carboxyl group (1663 cm?1).Its1H NMR spectrum showed three methyl groups (δH0.79,0.85,and 1.24) and two oxygenated protons (δH3.49 and 3.66).The13C NMR,DEPT,and HSQC spectra exhibited 15 carbon resonances,including three methyl groups(δC19.1,21.4,and 24.1),five methylenes (δC20.2,23.8,31.3,36.3,and 67.1),two methines (δC30.7 and 38.7),five non-protonated carbons (including two oxygenated methines atδC73.4 and 74.1;two olefinic carbons atδC137.2 and 159.6;one carboxyl carbon atδC202.7).The aforementioned NMR data of 4 (Table 2) revealed that it was also a cadinane-type sesquiterpene.The structure of 4 was found to be closely related to that of (4α,10β)-4,10-dihydroxycadin-1(6)-ene-5-one [22],with the main difference being that the CH3-14 in the latter was replaced by a hydroxy group-substituted methylene in 4.The above observation could be further confirmed by key HMBC correlations from H-14a (δH3.66) and H-14b (δH3.49) to C-1 (δC159.6),C-9 (δC31.3),and C-10 (δC74.1).However,due to signal overlap in the1H spectrum (H-7 and H-2;H-8a and H-8b,for example),it was difficult to elucidate the relative configuration of 4 through ROESY correlations.Then,four possible diastereoisomers of 4,(4S*,7R*,10S*)-4 (4a),(4S*,7R*,10R*)-4 (4b),(4S*,7S*,10R*)-4 (4c),and (4S*,7S*,10S*)-4 (4d) were subjected to quantum chemical calculation of NMR chemical shifts.According to the computational results (Table 3),the relative configuration of 4 was determined as 4S*,7R*,and 10S*.However,as the situation in 3,TDDFT calculation failed to produce the experimental ECD curve of 4.Thus,the absolute configuration of 4 was left undermined.Thus,the structure of 4 was determined as 4,10,14-trihydroxycadin-1(6)-en-5-one.

Table 2 1H and 13C NMR spectroscopic data for compounds 3 and 4 (δ in ppm,J in Hz)

Table 3 The results for NMR computation of compounds 2—4

The structures of those known compounds,including(4R)-4-hydroxy-1,10-seco-muurol-5-ene-1,10-dione (5)[21],(4S)-4-hydroxy-1,10-seco-muurol-5-ene-1,10-dione(6) [21],kadlongirin A (7) [17],rel-(2R,3R,4S,5S)-tetrahydro-3,4-dimethyl-2,5-bis(3,4,5-trimethoxyphenyl) furan(8) [23],prinsepiol (9) [24],8α-hydroxypinoresinol (10)[25],ginkgool (11) [26],massoiresinol (12) [27],acanthosessilin A (13) [28] were identified by comparing their spectroscopic data with those reported in literature.

Additionally,compounds (?)-1,(+)-1,2,3,5,and 6 were evaluated for their protective effects against damage of PC12 cells induced by corticosterone.As a result,compounds 5 and 6 showed moderate activities (Table 4),which indicated their potential neuroprotective activities.

Table 4 Protective activities of selected compounds against corticosterone?induced apoptosis in PC12 Cells

3 Experimental section

3.1 General

HRESIMS data were acquired on an Agilent 6540 QSTAR TOF time-of-flight mass spectrometer (Agilent Corp.,America).A Tensor 27 spectrophotometer (BrukerCorp.,Switzerland) was used for scanning IR spectroscopy with KBr pellets.UV spectra were obtained using a Shimadzu UV-2401 PC spectrophotometer (Shimadzu Corp.,Japan).Experimental ECD spectra were measured on a Chirascan V100 instrument (Applied Photophysics Limited,Britain).Optical rotations were measured with a JASCO P-1020 polarimeter (Jasco Corp.,Japan).Crystallographic data were obtained on a Bruker APEX DUO(Bruker Corp.,Switzerland).1D and 2D NMR spectra were recorded on Bruker AV III 500 MHz,Bruker DRX-600,or Bruker Ascend 800 MHz spectrometers (Bruker Corp.,Switzerland) with TMS internal standard.Chemical shifts (δ) are expressed in ppm relative to the solvent signals.Semi-preparative HPLC was performed on an Agilent 1260 liquid chromatography (Agilent Corp.,America) with a Zorbax SB-C18 (4.6 mm × 250 mm)column and a CHIRALPAK IC (4.6 mm × 250 mm) column.Column chromatography (CC) was performed with silica gel (80–100,100–200 and 200–300 mesh;Qingdao Marine Chemical,Inc.,Qingdao,People’s Republic of China).MCI gel (75–150 μm,Mitsubishi Chemical Corporation,Tokyo,Japan),Lichroprep RP-18 gel (40–63 μm,Merck,Darmstadt,Germany),Sephadex LH-20((Pharmacia,Uppsala,Sweden) and SEPAFlash column(Spherical C-18,20–45 μm,100 ?m).Fractions were monitored by thin layer chromatography and spots were detected with 10% H2SO4in EtOH.

3.2 Plant material

The stems ofSchisandra bicolorvar.tuberculatawere collected in Tongren region,Guizhou Province,China,in April 2020,and identified by Prof.Heng Li,Kunming Institute of Botany.A voucher specimen has been deposited in the Herbarium of the Kunming Institute of Botany,Chinese Academy of Sciences.

3.3 Bioactivity evaluation

Poorly differentiated PC12 cells were maintained in DMEM medium supplemented with 10% fetal bovine serum (FBS),penicillin (100 U/mL),streptomycin(100 μg/mL),and incubated at 5% CO2and 37 ℃.Poorly differentiated PC12 cells were divided into the following groups: untreated,CORT (150 μmol/L),CORT(150 mol/l) plus DIM (10 μmol/L),CORT (150 μmol/L)plus test compounds (20 μmol/L).Briefly,poorly differentiated PC12 cells were seeded into 96-well culture plates at a density of 1 × 104cells/well.After 24 h culturing,the wells were added compounds as previously described groups.48 h later,MTS solution was added to each well.The absorbance was measured at 492 nm using a Thermo Multiskan FC [29].

3.4 Extraction and isolation

Air-dried and powdered stems (10.5 kg) ofS.bicolorvar.tuberculatawere extracted with 70% aqueous Me2CO(3 × 40 l) to yield an extract at room temperature to give a crude extract (1081 g),which was extracted with EtOAc.The EtOAc part (380 g) was separated by a silica gel column and eluted with a CHCl3/Me2CO gradient system(1:0 to 0:1) to afford five fractions A–E.Fractions B (45 g)and C (51 g) were successively decolorized on MCI gel with MeOH/H2O (90:10) to obtain B1 and C1.Fraction B1(42 g) was subjected to ODS chromatography and eluted with MeOH/H2O (50:50 to 100:0) to give six fractions(B1a–B1f).Then B1a (18 g) was repeatedly subjected to silica gel column to obtain 8 (300 mg),other fractions further purified by preparative HPLC to afford 5 (30 mg) and 6(20.0 mg).Fraction B1b (14 g) was repeatedly subjected to silica gel column,then purified by semi-preparative HPLC to give 1 (13.5 mg),2 (3.0 mg) and 7 (2.9 mg).Fraction C1(44 g) was subjected to ODS chromatography by eluting with MeOH/H2O (30:70 to 100:0) to give seven fractions.C1b (4.52 g) was chromatographed on flash column by eluting with MeOH/H2O (20:80 to 60:40) to yield 12 fractions bF1–bF12,and bF2 (850 mg) was then subjected to Sephadex LH-20 (CHCl3/MeOH,1:1),and further purified by semi-preparative HPLC to give 3 (3.49 mg),and 4 (4.35 mg),9 (10 mg),10 (2.62 mg),11 (3.71 mg).Fraction bF4 (420 mg) was subjected to Sephadex LH-20(CHCl3-MeOH,1:1),and further purified by semi-preparative HPLC to give 12 (5.40 mg) and 13 (3.71 mg).

3.5 Physical constants and spectroscopic data of compounds

(?)-Schibiculatin A [(?)-(1)]: colorless crystals,[α] ? 37.45,(c0.110,MeOH),UV (MeOH)λmax(logε) 206(4.96),258 (3.24),272 (3.40) nm.CD (CH3OH,c0.05):198 nm (Δε=? 11.19),208 nm (Δε=31.90),217 nm(Δε=0.73),221 nm (Δε=1.60),240 nm (Δε=? 7.31).IR (KBr)νmax3436,2958,2935,1630,1594,1507,1463,1128 cm?1.ESIMSm/z252 [M+Na]+,HRESIMSm/z501.2102 [M+Na]+(calcd for C25H34O9Na 501.2095).1H NMR (methanol-d4,600 MHz) and13C NMR (methanold4,150 MHz),see Table 1.

(+)-Schibiculatin A [(+)-(1)]: colorless crystals,[α] + 31.38 (c0.087,MeOH),UV (MeOH)λmax(logε) 206(4.93),259 (3.57),268 (3.62) nm.ECD (CH3OH,c0.05):198 nm (Δε=17.07),208 nm (Δε=? 22.21),217 nm(Δε=4.14),221 nm (Δε=9.23),240 nm (Δε=3.03).IR (KBr)νmax3436,2958,2935,1630,1594,1507,1463,1128 cm?1.ESIMSm/z478 [M+Na]+,HRESIMSm/z501.2102 [M+Na]+(calcd for C25H34O9Na 501.2095).1H NMR (methanol-d4,600 MHz) and13C NMR (methanold4,150 MHz),see Table 1.

Schibiculatin B (2): colorless oil,[α] + 15.91 (c0.093,MeOH),UV (MeOH)λmax(logε) 202 (4.60),256 (3.71),281(3.91) nm.IR (KBr)νmax2938,2922,1737,1721,1649,1584,1511,1463,1416,1128 cm?1.ESIMSm/z437 [M+Na]+,HRESIMSm/z437.1566 [M+Na]+(calcd for C23H28O8Na 437.1571).1H NMR (chloroform-d,600 MHz) and13C NMR (chloroform-d,150 MHz),see Table 1.

Schibiculatin C (3): colorless oil,[α] + 25.2 (c0.090,MeOH),UV (MeOH)λmax(logε) 195 (3.74)nm.ECD (CH3OH,c0.36): 199 nm (Δε=3.03),214 nm (Δε=? 2.01).IR (KBr)νmax3428,2966,2921,2859,1631,1560,1384,802 cm?1.ESIMSm/z275[M+Na]+,HRESIMSm/z275.1621 [M+Na]+(calcd for C15H24O3Na 275.1618).1H NMR (pyridine-d5,600 MHz)and13C NMR (pyridine-d5,150 MHz),see Table 2.

Schibiculatin D (4): colorless oil,[α] ? 11.2 (c0.088,MeOH),UV (MeOH)λmax(logε) 216 (3.53) nm,248(3.88) nm.ECD (CH3OH,c0.26): 206 nm (Δε=2.69),248 nm (Δε=? 7.81),338 nm (Δε=1.95).IR (KBr)νmax3427,2958,2930,2859,1663,1611,1463,1383,1060 cm?1.ESIMSm/z268 [M+Na]+,HRESIMSm/z291.1566 [M+Na]+(calcd for C15H24O4Na 291.1567).1H NMR (methanol-d4,600 MHz) and13C NMR (methanold4,150 MHz),see Table 2.

Crystal data for (±)-schibiculatin A [(±)-1]:C25H34O9,M=478.52,a=7.9385(2) ?,b=9.5977(3)?,c=17.1002(5) ?,α=86.9070(10)°,β=84.8510(10)°,γ=66.3110(10)°,V=1188.06(6) ?3,T=100.(2) K,space groupP-1,Z=2,μ(Cu Kα)=0.843 mm?1,39,839 reflections measured,4665 independent reflections(Rint=0.0409).The finalR1values were 0.0343 (I>2σ(I)).The finalwR(F2) values were 0.0865 (I>2σ(I)).The finalR1values were 0.0368 (all data).The finalwR(F2) values were 0.0882 (all data).The goodness of fit onF2was 1.069.Crystallographic data for the structure of (±)-schibiculatin A [(±)-1] have been deposited in the Cambridge Crystallographic Data Centre (deposition number CCDC 2145390).Copies of the data can be obtained free of charge from the CCDC via www.ccdc.cam.ac.uk.

Supplementary Information

The online version contains supplementary material available at https:// doi.org/ 10.1007/ s13659?022?00342?3.

Additional file 1.It includes 1D NMR,2D NMR,HRESIMS,UV,ECD,IR,OR,and computational data of compounds 1—4,and methods for quantum chemical calculations are available.

Acknowledgements

We thank Service Center for Bioactivity Screening,State Key Laboratory of Phytochemistry and Plant Resources in West China,Kunming Institute of Botany for bioactivity screening.This project was supported financially by the National Natural Science Foundation of China (No.81903520).

Author contributions

PTP conceived and designed the research;SMZ,KH carried out the experi?ment and wrote the manuscript;PTP,HDS and KH supervised the whole study and critically reviewed the manuscript;XNL determined crystal structure of(±)?1 by X?ray diffraction analysis.All authors read and approved the final manuscript.

Declarations

Competing interests

No conflict of interest is declared.

Author details

1State Key Laboratory of Phytochemistry and Plant Resources in West China,Yunnan Key Laboratory of Natural Medicinal Chemistry,Kunming Institute of Botany,Chinese Academy of Sciences,Kunming 650201,People’s Republic of China.2University of Chinese Academy of Sciences,Beijing 10039,People’s Republic of China.