English

• 1.   Introduction

  The Microdesmis genus (Pandaceae family) consists of 10 species that mainly distributed in African, and tropical and subtropical Asian countries.^[1] Only one specie, Microdesmis casearifolia grows in China, which has been applied as folk medicine in China for the treatment of hemostasis swelling, ringworm, wart, and teeth pain. Previous chemical investigations on Microdesmis plants led to the isolation of diverse compound classes, including spermidines, ^[2-5] quinoline alkaloids^[6] and terpenoids.^[7] Terpenoids, widely distributed in nature and exhibiting various biological activities, are important sources of lead compounds in drug discovery. In the continuation of our ongoing project for the discovery of novel diterpenoids from medicinal plants, ^[8-13] an initial chemical study on the twigs and leaves of M. casearifolia was carried out for the first time, which afforded four new diterpenoids, casearoids A~D (1~4), representing four different types. Their structures were completely elucidated on the basis of comprehensive analysis of the spectroscopic data, as well as time dependent density functional theory (TDDFT)- based electronic circular dichroism (ECD) calculation.

  2.   Results and discussion

  Casearoids A (1) had a molecular formula of C₂₀H₃₀O₃ as established by the protonated HRESIMS ion peak at m/z 319.2263 [M+H]⁺ (calcd 319.2268) and ¹³C NMR data, suggestive of six indices of hydrogen deficiency (IHD). The IR spectrum showed the presence of hydroxy (3451 cm^-1), carbonyl (1713 cm^-1) and vinyl (1663 cm^-1) functional groups. Its ¹³C NMR data combined with distortionless enhancement by polarization transfer (DEPT) experiments (Table 1) revealed the presence of four methyls, seven methylenes (one oxygenated), two methines, three sp³ quaternary carbons, two carbonyl carbons (δ_C 200.2 and 215.3) and one trisubstituted double bonds. The abovementioned functional groups accounted for three out of the six IHDs, which demanded compound 1 to possess three rings in the structure.

  Table 1

  

  Table 1.  ¹H NMR (600 MHz) and ¹³C NMR (125 MHz) data for compounds 1~4

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  No.	1a			2a			3a			4a
  	δH (J in Hz)	δC		δH (J in Hz)	δC		δH (J in Hz)	δC		δH (J in Hz)	δC
  1	α 2.34, dd (17.5, 14.0)	34.6		5.99, d (2.7)	123.1		α 1.21, dt (12.9, 3.8)	37.0		1.48~1.52, m	47.6
  	β 2.44, dd (17.5, 3.7)						β 1.80, td (12.9, 3.6)
  2		200.2			200.3		α 1.71~1.74, m	28.1		α 2.15~2.19, m	29.5
  							β 1.60~1.63, m			β 1.79~1.85, m
  3	5.71, s	125.7		α 2.17, d (1.5)	53.5		3.99, dd (11.7, 4.3)	78.8		5.06~5.09, m	124.9
  				β 2.33, d (1.5)
  4		172.1			36.9			39.1			134.9
  5		40.3		2.54, ddd (13.8, 5.0, 2.8)	44.7		1.16, dd (12.9, 2.6)	52.3		2.10~2.13, m	39.3
  6	α 1.87~1.90, m	36.2		α 1.86~1.89, m	17.8		α 2.11, ddd (12.1, 5.6, 2.6)	33.4		2.15~2.17, m	25.0
  	β 1.46~1.50, m			β 1.39~1.45, m			β 1.31~1.38, m
  7	α1.50~1.52, m	25.4		α 1.35~1.38, m	24.9		3.99, dd (10.8, 5.6)	73.8		5.06~5.09, m	130.6
  	β 1.30~1.33, m			β 1.73~1.76, m
  8	1.35~1.39, m	41.3		1.76~1.79, m	30.5			152.0			128.4
  9		36.8			38.4		1.63~1.67, m	55.0		α 2.44, dd (13.5, 7.5)	42.2
  										β 2.48, dd (13.5, 3.9)
  10	1.74, dd (14.0, 3.7)	52.9			174.1			39.1		5.00~5.03, m	80.0
  11	α 1.60, t (13.1)	33.8		α 1.79~1.83, m	33.4		α 2.36, ddd (15.5, 6.8, 3.5)	23.2		7.17, d (1.8)	147.8
  	β 1.12, td (14.0, 4.8)			β 1.49~1.52, m			β 2.24, ddd (15.5, 11.1, 6.8)
  12	α 1.84, td (14.0, 4.8)	27.9		α 1.83~1.85, m	28.9		5.37, t (6.6)	133.0			134.9
  	β 1.43, ddt (11.8, 4.8, 2.5)			β 1.54~1.56, m
  13		45.6			45.4			134.0		2.42, td (4.9, 2.1)	23.6
  14	α 1.58~1.63, m	35.2		α 1.49~1.52, m	35.8		6.31, dd (17.4, 10.7)	141.6		α 1.83~1.89, m	26.6
  	β 1.23~1.25, m			β 1.42~1.44, m						β 1.54~1.58, m
  15		215.3			215.1		a 5.06, d (17.4)	110.4			74.2
  							b 4.89, d (10.7)
  16	4.39, s	64.0		4.41, s	64.1		1.75, br s	12.0		1.25, s	27.6
  17	1.21, s	20.7		1.19, s	19.7		a 5.19, br s	104.7		1.23, s	28.1
  							b 4.66, br s
  18	1.89, br s	19.0		1.03, s	19.0		0.80, s	15.6		1.60, s	15.4
  19	1.13, s	19.2		1.09, s	29.0		1.03, s	28.5		1.64, s	18.2
  20	0.85, s	12.3		0.83, s	20.1		0.73, s	14.6			174.4
  a Measured in CDCl3.

  The planar structure of 1 was constructed by the interpretation of the 2D NMR spectra (Figure 1A). Briefly, the ¹H-¹H COSY correlations of 1 indicated three spin systems as sketched in bold lines, which were then connected with the quaternary carbons and oxygen atoms by the HMBC analysis (Figure 1A) to furnish the diterpenoid framework.Combining with the ¹H-¹H COSY correlations of H₂-1/ H-10, the HMBC correlations of H-3/C-1 and C-2; H₃-19/ C-4, C-5, C-6 and C-10; and H₃-20/C-3, C-4, and C-5 established the A-ring incorporating an α, β-unsatu- rated ketone and bearing two methyls at C-4 and C-5. The B and C rings with two methyl groups at C-9 and C-13 were delineated by the ¹H-¹H COSY correlations of H₂-6/H₂-7/ H-8/H₂-14 and H₂-11/H₂-12, together with the key HMBC correlations of H₂-11/C-8, C-10, and C-13; H₃-17/C-12, C-13, C-14 and C-15; H₃-18/C-8, C-9, C-10, and C-11; and H₃-19/C-4, C-5, and C-6. Additionally, a hydroxyacetyl group was attached at C-13 by the key HMBC correlations of H₂-16/C-13 and C-15, and H₃-17/ C-15. The 2D structure of compound 1 was thus constructed as shown with a dolabrane framework, which is similar to that of ent- 5α, 2, 15-dioxodolabr-3-ene-3, 16-di- ol.^{[8, 14]}

  Figure 1

  

  Figure 1.  Key 2D NMR correlations of compound 1

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  The relative configuration of 1 was determined by the NOESY analysis (Figure 1B). The NOESY cross-peaks of H₃-18 with H-1α and H₃-19 indicated that these protons were in the same side of the molecule, and were arbitrarily assigned in a α-orientation. Accordingly, H-6β, H-8, H-10, and Me-17 were assigned as β-orientation on the basis of the NOESY correlations of H-10/H-6β and H-8, as well as H₃-17/H-8. The absolute configuration of 1 was determined as depicted by comparing the experimental ECD spectrum of 1 with the calculated ECD curves. As shown in Figure 2, the calculated ECD spectrum was roughly matched that of the experimental one, which established the absolute configuration of 1 as 5R, 8S, 9S, 10R, 13S.

  Figure 2

  

  Figure 2.  Experimental and calculated ECD spectra of compound 1

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  The molecular formula of casearoids B (2) was determined to be C₂₀H₃₀O₃ by the (+)-HRESIMS ion peak at m/z 341.2096 [M+Na]⁺ (calcd 341.2087, C₂₀H₃₁NaO₃) and ¹³C NMR data. The IR absorptions at 3446, 1715 and 1668 cm^-1 indicated the presence of hydroxy, carbonyl and olefin groups, respectively. With the aid of DEPT and HSQC experiments, its ¹H and ¹³C NMR spectra (Table 1) indicated the presence of four methyls, seven methylenes (one oxygenated), two methines, three sp³ quaternary carbons, two carbonyl carbons (δ_C 200.4 and 215.1), and one trisubstituted double bond. Comparison of its NMR data with those of compound 1 (Table 1) revealed that they are structural analogs, and the major changes occurred at the A-ring. Two geminal methyls were attached at C-4 in the A ring of 2 replacing the 4, 5-dimethyl substitution of the former by the HMBC correlation networks of H-1/C-2, C-5 and C-10; H-3/C-1 and C-2; and H₃-20 and H₃-19/C-3, C-4 and C-5. This was supported by the characteristic carbon resonances assignable for an α, β-unsaturated ketone in the A ring (Table 1). Compound 2 shared B and C rings bearing the same appendages with 1 were verified by the coupling correlations of H-5/H-6/H-7/H-8/H-14, and H-11/ H-12 in the ¹H-¹H COSY spectrum, as well as the key HMBC correlations of H-8/C-13; H₃-17/C-12, C-13 and C-14; H₃-18/C-8, C-9, C-10 and C-11; H₂-16/C-13 and C-15; and H₃-17/C-15 (Figure 3A).

  Figure 3

  

  Figure 3.  Key 2D NMR correlations of compound 2

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  The relative structure of compound 2 was elucidated by the NOESY analysis (Figure 3B), in which the NOESY correlations of H-5 with H-8, and H₃-19, and H₃-17/H-8 indicated that H-5, H-8, Me-17 and Me-19 were in the same side of the molecule, and were randomly assigned in a β-orientation. Consequently, the NOESY correlations of H-6α with H₃-20, H₃-18 indicated that these protons were α-directed. The absolute configuration of 2 was determined as 5R, 8S, 9S, 13S by its compatible ECD curves between the experimental ECD spectrum and the calculated one (Figure 4).

  Figure 4

  

  Figure 4.  Experimental and calculated ECD spectra of compound 2

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  Casearoids C (3) gave a molecular formula of C₂₀H₃₂O₂ with five IHDs based on its HRESIMS and ¹³C NMR data. Its 1D NMR data (Table 1) showed the existence of four methyls, four methylenes, four methines (two oxygenated), two quaternary carbons, and three double bonds (one monosubstituted, one disubstituted and one trisubstituted) in 3. These functional groups accounted for three IHDs, and the remaining two IHDs required compound 3 to be bicyclic. The planar structure of 3 was determined by the 2D NMR analysis (Figure 5A), in which four spin systems (i, ii, iii and iiii) as depicted with bold bonds were identified by the ¹H-¹H COSY correlations. The HMBC correlations of H₃-18/C-1, C-5 and C-10, and H₃-19(20)/C-3, C-4 and C-5 forged A ring with a hydroxy group attached at C-3 (δ_C 78.8). The HMBC correlations of H₂-6/C-8 and C-10; H-7/C-8; H₂-17/C-7, C-8 and C-9; H₃-18/C-5, C-9 and C-10 furnished the B ring with the appendages of an exocyclic △⁸⁽¹⁷⁾ double bond and a hydroxy group at C-7 (δ_C 73.8). Finally, a 3-methylpenta-1, 3-diene motif was identified and attached to C-9 based on the ¹H-¹H COSY correlations of H-9/H₂-11/H-12 (fragment iii) and H-14/H-15 (fragment iiii), as well as the HMBC correlations of H-14/C-12, and H₃-16/C-12, C-13 and C-14. Thus, compound 3 was determined to be a new labdane diterpeniod.^[10]

  Figure 5

  

  Figure 5.  Key 2D NMR correlations of compound 3

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  The relative configuration of 3 was determined as shown by analysis of the NOESY data (Figure 5B). In details, the NOESY cross-peaks of H-3 with H-5 and H₃-19; H-5 with H-7; and H-7 with H-9 revealed that these protons were cofacial and arbitrarily assigned as α-oriented. The mutual NOESY correlations among H₃-18, H₃-20 and H-6β then indicated that they were β-oriented. The E-geometry of the Δ¹² double bond was assigned by the NOESY correlations of H₂-11/H₃-16, and H-12/H-14. The absolute configuration of 3 was determined as 3S, 5R, 7S, 9R, 10S by the highly similarities between the experimental ECD and the calculated ECD spectra (Figure 6).

  Figure 6

  

  Figure 6.  Experimental and calculated ECD spectra of compound 3

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  The molecular formula of casearoids D (4) was assigned as C₂₀H₃₀O₃ with six IHDs by the (+)-HRESIMS ion peak at m/z 341.2080 [M+Na]⁺ (calcd for C₂₀H₃₀NaO₃, 341.2087) and the ¹³C NMR data. With the assistance of DEPT and HSQC experiments, twenty carbon resonances (Table 1) were classified as four methyls, six methylenes, two methines (one oxygenated), one oxygenated tertiary carbon, three trisubstituted double bonds, and one carbonyl carbon (δ_C 174.4). The carbonyls and the double bonds accounted for four IHDs, and the remaining ones thus required the presence of two rings in compound 4. Detailed examination of the 2D NMR spectra constructed the 2D structure of 4. Analysis of the ¹H-¹H COSY spectrum revealed four structural units as depicted with bold bonds (Figure 7A), which were connected with the other functional elements to furnish the 14-membered macrocyclic framework by the HMBC correlations of H₂-2/C-1 and C-14; H₂-5/C-6 and C-7; H-11/H-12 and H-13; H₃-18/C-3, C-4 and C-5; and H₃-19/C-7, C-8 and C-9. Additionally, a hydroxyisopropyl group (δ_C-15 74.2)^[13] was attached to C-1 based on the HMBC correlations of H₃-16(17)/C-1 and C-15. The remaining one IHD, as well as the key HMBC correlations from H-11 and H₂-13 to C-20 (δ_C 174.4) indicated the existence of a α, β-unsaturated γ-lactone between C-10 and C-20, which was supported by the C-10 chemical shift at δ_C 80.0.^[15-17] The 2D structure of 4 was thus delineated to be a cembrane analog.

  Figure 7

  

  Figure 7.  Key 2D NMR correlations of compound 4

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  The relative configuration of 4 was determined by the NOESY experiment (Figure 7B). The NOESY cross-peaks of H-10 with H-9β and H₃-19, and H-11 with H-1 and H-10, and H-1 with H-2β revealed that they were cofacial and arbitrarily assigned as β-oriented. As a consequence, the NOESY correlation of H-2α/H₃-18 permitted the Me-18 to be α-oriented. The E-geometry for Δ³ and Δ⁷ double bonds were unambiguously assigned by the NOESY correlations of H-3/H₂-5 and H-2α/H₃-18; and H-7/H-9α and H₂-6/H₃-19, respectively. The absolute configuration of 4 was determined as 1R, 10R by the roughly matched experimental ECD spectrum and the calculated one (Figure 8). To further reinforce the structure of 4, calculations of ¹³C NMR chemical shifts of 4 and its 1R, 10S isomer using Gauge-Independent Atomic Orbitals (GIAO) method were performed at B3LYP/6-31G(d, p) level. The results indicated that the 1R, 10R isomer showed higher correlation coefficient (R², 0.99924) (Figure 9) and lower mean absolute deviation than those of the 1R, 10S isomer, which further confirmed the 1R, 10R configuration for 4.

  Figure 8

  

  Figure 8.  Experimental and calculated ECD spectra of compound 4

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  Figure 9

  

  Figure 9.  Experimental and calculated ¹³C NMR chemical shifts of compound 4

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  3.   Conclusions

  Our preliminary chemical investigation on Microdesmis casearifolia led to the isolation and identification of four new diterpenoids casearoids A~D (1~4). Their structures with absolute configurations were elucidated by spectroscopic data analysis and ECD calculation. This study is a valuable collection for the diverse diterpenoids of natural products, and provides initial information on the chemical composition of the titled plant.

  4.   Experimental section

  4.1   Plant material

  The twigs of Microdesmis casearifolia were collected from Hainan Province, People's Republic of China. The plant sample was authenticated by Prof. Shi-Man Huang at Hainan University. A voucher specimen has been kept in our institute (accession number: Micas-2011-1Y).

  4.2   Extraction and isolation

  The dried sample powder (10 kg) was extracted at room temperature with 95% (volume fraction) EtOH for tree times to obtain the crude extract (240 g). The crude was then dissolved in 3 L of water to give a suspension, and partitioned with EtOAc. The EtOAc-soluble part (65 g) was chromatographed over D101-macroporous absorption resin, eluting with 50%, 80%, and 95% EtOH in H₂O sequentially, to give fractions F1~F3.

  F2 (25 g) was separated on a column of MCI gel and eluted with gradients of MeOH/H₂O (30%~100%, volume fraction) to give five sub-fractions F2a~F2e. The F2a (3.3 g) containing mainly diterpenoids was separated on a silica gel column eluted with petroleum ether/acetone (V: V=20:1 to 1:1) in gradient to yield fractions F2a1~F2a9. Fraction F2a2 (58 mg) was separated by semi-pre- parative high performance liquid chromatography (HPLC) (65% acetonitrile in water as the mobile phase) to yield compounds 1 (3 mg), 2 (2 mg), 3 (2 mg) and 4 (2 mg).

  Casearoids A (1): Yellow liquid. [α]_D^17.8 -11.0 (c 0.4 in MeOH); UV/Vis (MeOH) λ_max [log ε/(L•mol^-1•cm^-1)]: 193 (3.56), 207 (3.45), 239 (3.85) nm; ECD (MeOH) λ [Δε/ (L•mol^-1•cm^-1)]: 192 (0.42), 211 (-4.36), 241 (3.79), 322 (-0.95) nm; IR (KBr) ν_max: 3451, 2928, 2858, 1713, 1663, 1458, 1378, 1283, 1261, 736 cm^-1; ¹H NMR (CDCl₃) and ¹³C NMR (CDCl₃) see Table 1; (+)-ESIMS m/z: 341.5 [M+Na]⁺; (-)-ESIMS m/z 317.6 [M-H]^-; (+)- HRESIMS calcd for C₂₀H₃₁O₃ [M+H]⁺ 319.2268, found 319.2263.

  Casearoids B (2): Yellow liquid. [α]_D^17.7 -10.0 (c 0.07 in MeOH); UV/Vis (MeOH) λ_max [log ε/(L•mol^-1•cm^-1)]: 195 (3.60), 239 (3.30) nm; ECD (MeOH) λ [Δε/(L•mol^-1• cm^-1)]: 192 (1.57), 228 (0.80), 289 (-0.41) nm; IR (KBr) ν_max: 3446, 2926, 2854, 1715, 1668, 1456, 1374, 1260, 1098, 1029, 802 cm^-1; ¹H NMR (CDCl₃) and ¹³C NMR (CDCl₃), see Table 1; (+)-ESIMS m/z: 341.3 [M+Na]⁺; (+)-HRESIMS calcd for C₂₀H₃₁NaO₃ [M+Na]⁺ 341.2087, found 341.2096.

  Casearoids C (3): Yellow liquid. [α]_D^17.7 -4.5 (c 0.20 in MeOH); UV/Vis (MeOH) λ_max [log ε/(L•mol^-1•cm^-1)]: 195 (3.76), 229 (3.39) nm; ECD (MeOH) λ [Δε/(L•mol^-1• cm^-1)]: 192 (-1.74), 194(0.13), 197(0.58), 205 (0.19), 225 (-0.13) nm; IR (KBr) ν_max: 3391, 2923, 2852, 1716, 1668, 1456, 1261, 1089, 1025 cm^-1; ¹H NMR (CDCl₃) and ¹³C NMR (CDCl₃) see Table 1; (-)-ESIMS m/z 303.2 [M-H]^-; (+)-HRESIMS calcd for C₂₀H₃₂NaO₂ [M+ Na]⁺ 327.2295, found 327.2295.

  Casearoids D (4): Yellow liquid. [α]_D^17.9 -21.0 (c 0.1 in MeOH); UV/Vis (MeOH) λ_max [log ε/(L•mol^-1•cm^-1)]: 195 (3.73) nm; ECD (MeOH) λ [Δε/(L•mol^-1•cm^-1)]: 192 (2.76), 194 (0.23), 207 (1.24) nm; IR (KBr) ν_max: 3421, 2924, 2853, 1738, 1574, 1436, 1379, 1260, 1170, 1094, 1031, 804 cm^-1; ¹H NMR (CDCl₃) and ¹³C NMR (CDCl₃), see Table 1; (+)-ESIMS m/z: 341.4 [M+Na]⁺; (-)- ESIMS m/z: 317.8 [M-H]^-; (+)-HRESIMS calcd for C₂₀H₃₀NaO₃ [M+Na]⁺ 341.2087, found 341.2080.

  4.3   ¹³C NMR calculations

  ¹³C NMR chemical shifts calculations at B3LYP/6-31G (d, p) level based on the gauge independent atomic orbital (GIAO) and in solvent of chloroform (CPCM).

  4.4   ECD calculations

  The ChemDraw_Pro_15.0 software with an MM2 force field was used to establish the initial conformations of the target molecules. Conformational searches using mixed torsional/Low-mode sampling method with MMFFs force field in an energy window of 8.37 kJ/mol were carried out by means of the conformational search module in the Maestro 10.2 software (Maestro Technologies, Inc., Trenton, NJ, USA). The re-optimization and the following TDDFT calculations of the re-optimized conformations were all performed with the Gaussian 09 software (Gaussian, Inc., Wallingford, CT, USA)^[18] at the B3LYP/6-311G (d, p) level, in vacuo. Frequency analysis was performed as well to confirm that the re-optimized conformers were at the energy minima. Finally, the SpecDis 1.64 software (https://specdis-software.jimdo.com/)^[19] was used to obtain the Boltzmann-averaged ECD spectra.

  Supporting Information  General experimental procedures and chiral analysis, and 1D and 2D NMR, MS, and IR spectra of compounds 1~4. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn.

  
  
• 1. [1]

     Li, P. T.; Zhang, Y. T., In Flora of China, Vol. 43, Eds.: Xu, L. R.; Huang, C. J., Science Press, Beijing, 1998, p. 2.

  2. [2]

     Zamble, A.; Sahpaz, S.; Hennebelle, T.; Carato, P.; Bailleul, F. Chem. Biodiversity 2006, 3, 982. doi: 10.1002/cbdv.200690107

  3. [3]

     Zamble, A.; Sahpaz, S.; Brunet, C.; Bailleul, F. Phytomedicine 2008, 15, 625. doi: 10.1016/j.phymed.2007.10.002

  4. [4]

     Roumy, V.; Hennebelle, T.; Zamble, A.; Yao, J. D.; Sahpaz, S.; Bailleul, F. Eur. J. Mass Spectrom. 2008, 14, 111. doi: 10.1255/ejms.910

  5. [5]

     Zamble, A.; Martin-Nizard, F.; Sahpaz, S.; Reynaert, M.-L.; Staels, B.; Bordet, R.; Duriez, P.; Gressier, B.; Bailleul, F. Phytother. Res. 2009, 23, 892. doi: 10.1002/ptr.2717

  6. [6]

     Zamble, A.; Hennebelle, T.; Sahpaz, S.; Bailleul, F. Chem. Pharm. Bull. 2007, 55, 643. doi: 10.1248/cpb.55.643

  7. [7]

     Akpanyung, E. O.; Ita, S. O.; Opara, K. A.; Davies, K. G.; Ndem, J. I.; Uwah, A. F. J. Med. Plants Res. 2013, 7, 2338. doi: 10.5897/JMPR2013.5080

  8. [8]

     Ni, S.-J.; Li, J.; Li, M.-Y. Chem. Biodiversity 2018, 15, 1.

  9. [9]

     Yang, Y.; Zhang, Y.; Liu, D.; Min, L.; Weber; Shao, B.; Lin, W.-H. Fitoterapia 2015, 103, 277. doi: 10.1016/j.fitote.2015.04.016

  10. [10]

      Bohlmann, F.; Knoll, K. H.; King, R. M.; Robinson, H. Phytochemistry 1979, 18, 1997. doi: 10.1016/S0031-9422(00)82719-3

  11. [11]

      Ansell, S. M.; Pegel, K. H.; Taylor, D. A. H. Phytochemistry 1993, 32, 953. doi: 10.1016/0031-9422(93)85235-J

  12. [12]

      Jia, R.; Shi, Y.-H.; He, P.-M.; Guo, Y.-W. Chin. J. Nat. Med. 2010, 8, 422.

  13. [13]

      Duh, C.-Y.; Wang, S.-K.; Weng, Y.-L.; Chiang, M.-Y.; Dai, C.-F. J. Nat. Prod. 1999, 62, 1518. doi: 10.1021/np990212d

  14. [14]

      Kijjoa, A.; Polonia, M. A.; Pinto, M. M. M.; Kitiratakarn, T.; Gedris, T.; Herz, W. Phytochemistry 1994, 37, 197. doi: 10.1016/0031-9422(94)85024-0

  15. [15]

      Mulholland, D. A.; Langat, M. K.; Crouch, N. R.; Coley, H. M.; Mutambi, E. M.; Nuzillard, J. M. Phytochemistry 2010, 71, 1381. doi: 10.1016/j.phytochem.2010.05.014

  16. [16]

      Langat, M. K.; Crouch, N. R.; Smith, P. J.; Mulholland, D. A. J. Nat. Prod. 2011, 74, 2349. doi: 10.1021/np2002012

  17. [17]

      Kawakami, S.; Matsunami, K.; Otsuka, H.; Lhieochaiphant, D.; Lhieochaiphant, S. J. Nat. Med. 2013, 67, 410. doi: 10.1007/s11418-012-0693-4

  18. [18]

      Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M.A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R. E.; Stratmann, O.; Yazyev, A. J.; Austin, R.; Cammi, C.; Pomelli, J. W.; Ochterski, R.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J., Gaussian 09, Rev. B.01, 2010, Gaussian Inc., Wallingford CT.

  19. [19]

      Bruhn, T.; Schaumloeffel, A.; Hemberger, Y.; Bringmann, G. Chirality 2013, 25, 243. doi: 10.1002/chir.22138

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  Figure 1  Key 2D NMR correlations of compound 1

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  Figure 2  Experimental and calculated ECD spectra of compound 1

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  Figure 3  Key 2D NMR correlations of compound 2

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  Figure 4  Experimental and calculated ECD spectra of compound 2

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  Figure 5  Key 2D NMR correlations of compound 3

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  Figure 6  Experimental and calculated ECD spectra of compound 3

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  Figure 7  Key 2D NMR correlations of compound 4

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  Figure 8  Experimental and calculated ECD spectra of compound 4

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  Figure 9  Experimental and calculated ¹³C NMR chemical shifts of compound 4

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  Table 1.  ¹H NMR (600 MHz) and ¹³C NMR (125 MHz) data for compounds 1~4

  No.	1a			2a			3a			4a
  	δH (J in Hz)	δC		δH (J in Hz)	δC		δH (J in Hz)	δC		δH (J in Hz)	δC
  1	α 2.34, dd (17.5, 14.0)	34.6		5.99, d (2.7)	123.1		α 1.21, dt (12.9, 3.8)	37.0		1.48~1.52, m	47.6
  	β 2.44, dd (17.5, 3.7)						β 1.80, td (12.9, 3.6)
  2		200.2			200.3		α 1.71~1.74, m	28.1		α 2.15~2.19, m	29.5
  							β 1.60~1.63, m			β 1.79~1.85, m
  3	5.71, s	125.7		α 2.17, d (1.5)	53.5		3.99, dd (11.7, 4.3)	78.8		5.06~5.09, m	124.9
  				β 2.33, d (1.5)
  4		172.1			36.9			39.1			134.9
  5		40.3		2.54, ddd (13.8, 5.0, 2.8)	44.7		1.16, dd (12.9, 2.6)	52.3		2.10~2.13, m	39.3
  6	α 1.87~1.90, m	36.2		α 1.86~1.89, m	17.8		α 2.11, ddd (12.1, 5.6, 2.6)	33.4		2.15~2.17, m	25.0
  	β 1.46~1.50, m			β 1.39~1.45, m			β 1.31~1.38, m
  7	α1.50~1.52, m	25.4		α 1.35~1.38, m	24.9		3.99, dd (10.8, 5.6)	73.8		5.06~5.09, m	130.6
  	β 1.30~1.33, m			β 1.73~1.76, m
  8	1.35~1.39, m	41.3		1.76~1.79, m	30.5			152.0			128.4
  9		36.8			38.4		1.63~1.67, m	55.0		α 2.44, dd (13.5, 7.5)	42.2
  										β 2.48, dd (13.5, 3.9)
  10	1.74, dd (14.0, 3.7)	52.9			174.1			39.1		5.00~5.03, m	80.0
  11	α 1.60, t (13.1)	33.8		α 1.79~1.83, m	33.4		α 2.36, ddd (15.5, 6.8, 3.5)	23.2		7.17, d (1.8)	147.8
  	β 1.12, td (14.0, 4.8)			β 1.49~1.52, m			β 2.24, ddd (15.5, 11.1, 6.8)
  12	α 1.84, td (14.0, 4.8)	27.9		α 1.83~1.85, m	28.9		5.37, t (6.6)	133.0			134.9
  	β 1.43, ddt (11.8, 4.8, 2.5)			β 1.54~1.56, m
  13		45.6			45.4			134.0		2.42, td (4.9, 2.1)	23.6
  14	α 1.58~1.63, m	35.2		α 1.49~1.52, m	35.8		6.31, dd (17.4, 10.7)	141.6		α 1.83~1.89, m	26.6
  	β 1.23~1.25, m			β 1.42~1.44, m						β 1.54~1.58, m
  15		215.3			215.1		a 5.06, d (17.4)	110.4			74.2
  							b 4.89, d (10.7)
  16	4.39, s	64.0		4.41, s	64.1		1.75, br s	12.0		1.25, s	27.6
  17	1.21, s	20.7		1.19, s	19.7		a 5.19, br s	104.7		1.23, s	28.1
  							b 4.66, br s
  18	1.89, br s	19.0		1.03, s	19.0		0.80, s	15.6		1.60, s	15.4
  19	1.13, s	19.2		1.09, s	29.0		1.03, s	28.5		1.64, s	18.2
  20	0.85, s	12.3		0.83, s	20.1		0.73, s	14.6			174.4
  a Measured in CDCl3.

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