Purification, characterization, crystal structure and NO production inhibitory activity of three new sesquiterpenoids from homalomena occulta

Zhang, Q.; Ma, L.; Qu, Z.; Hou, G.; Wang, Y.; Wang, C.; Zhao, F.

doi:10.1107/S2053229618013815

Buy article online - an online subscription or single-article purchase is required to access this article.

Purification, characterization, crystal structure and NO production inhibitory activity of three new sesquiterpenoids from homalomena occulta

Q. Zhang, L. Ma, Z. Qu, G. Hou, Y. Wang, C. Wang and F. Zhao

Two new isodaucane-type sesquiterpenoids, namely (1R,4S,5S,6R,7S,10R)-isodauc-6,7,10-triol, C₁₅H₂₈O₃, (1), and (1R,4S,5S,6S,7S,10R)-isodauc-6,7,10-triol, (2), and a new eudesmane-type sesquiterpenoid, 1β,4β,5α-trihydroxyeudesmane, (3), were obtained from the rhizomes of homalomena occulta with the aid of column chromatography. Their structures were elucidated based on extensive spectroscopic analyses, including 1D NMR, 2D NMR and HRESIMS. The structure of (1) was confirmed by single-crystal X-ray diffraction and the absolute configuration was assigned with respect to that of the precursor. The single-crystal structure reveals that adjacent molecules of (1) embrace through two groups of intermolecular O—H

O hydrogen bonds to generate a two-dimensional sheet with a 6³-net topology. The three compounds were evaluated for their activity against lipopolysaccharide-induced production of nitrogen oxide (NO) in RAW 264.7 cells, and (1) showed an inhibitory effect on NO production, with IC₅₀ values of 5.7±0.22 µM.

Keywords: isodaucane; eudesmane; sesquiterpenoid; crystal structure; NO production inhibition.

Read article Similar articles

Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229618013815/lf3081sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S2053229618013815/lf3081Isup2.hkl Contains datablock I
	Portable Document Format (PDF) file https://doi.org/10.1107/S2053229618013815/lf3081sup3.pdf NMR spectra

CCDC reference: 1870837

Computing details top

Data collection: FRAMBO (Bruker, 2004); cell refinement: FRAMBO (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

(1R,4S,5S,6R,7S,10R)-Isodauc-6,7,10-triol top

Crystal data top

C₁₅H₂₈O₃	D_x = 1.164 Mg m⁻³
M_r = 256.37	Cu Kα radiation, λ = 1.54178 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 1647 reflections
a = 6.4636 (6) Å	θ = 4.2–71.9°
b = 12.9225 (12) Å	µ = 0.62 mm⁻¹
c = 17.516 (2) Å	T = 293 K
V = 1463.1 (3) Å³	Block, colourless
Z = 4	0.40 × 0.14 × 0.11 mm
F(000) = 568

Data collection top

Bruker Xcalibur Eos Gemini diffractometer	1969 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.053
CCD plate scans	θ_max = 66.1°, θ_min = 4.3°
Absorption correction: multi-scan (SADABS; Bruker, 2004)	h = −7→4
T_min = 0.789, T_max = 0.935	k = −15→14
8351 measured reflections	l = −20→19
2554 independent reflections

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.049	w = 1/[σ²(F_o²) + (0.0467P)² + 0.1932P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.126	(Δ/σ)_max < 0.001
S = 1.08	Δρ_max = 0.12 e Å⁻³
2554 reflections	Δρ_min = −0.16 e Å⁻³
170 parameters	Absolute structure: Flack x determined using 642 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
0 restraints	Absolute structure parameter: 0.1 (3)

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.7838 (5)	0.1931 (3)	0.3122 (2)	0.0393 (9)
C2	0.5989 (6)	0.1540 (3)	0.3597 (2)	0.0466 (10)
H2A	0.4856	0.1334	0.3268	0.056*
H2B	0.6390	0.0952	0.3909	0.056*
C3	0.5367 (6)	0.2444 (3)	0.4094 (2)	0.0486 (10)
H3A	0.6317	0.2531	0.4517	0.058*
H3B	0.3976	0.2355	0.4291	0.058*
C4	0.5483 (6)	0.3369 (3)	0.3540 (2)	0.0415 (9)
H4	0.4165	0.3385	0.3263	0.050*
C5	0.7177 (5)	0.3089 (3)	0.2946 (2)	0.0375 (8)
H5	0.8375	0.3539	0.3032	0.045*
C6	0.6398 (6)	0.3258 (3)	0.2130 (2)	0.0414 (9)
H6	0.5439	0.2695	0.2006	0.050*
C7	0.8138 (6)	0.3275 (3)	0.1501 (2)	0.0452 (9)
C8	1.0105 (6)	0.2697 (3)	0.1724 (3)	0.0502 (10)
H8A	1.0676	0.3028	0.2174	0.060*
H8B	1.1102	0.2783	0.1315	0.060*
C9	0.9903 (6)	0.1542 (3)	0.1890 (2)	0.0499 (10)
H9A	0.9740	0.1178	0.1410	0.060*
H9B	1.1181	0.1303	0.2122	0.060*
C10	0.8120 (6)	0.1249 (3)	0.2410 (2)	0.0425 (9)
H10	0.6841	0.1281	0.2111	0.051*
C11	0.5718 (6)	0.4429 (3)	0.3931 (2)	0.0482 (10)
H11	0.5858	0.4947	0.3526	0.058*
C12	0.3774 (7)	0.4700 (4)	0.4380 (3)	0.0700 (14)
H12A	0.3566	0.4197	0.4776	0.105*
H12B	0.2602	0.4698	0.4043	0.105*
H12C	0.3927	0.5374	0.4603	0.105*
C13	0.7628 (7)	0.4518 (3)	0.4435 (3)	0.0653 (13)
H13A	0.7477	0.4075	0.4871	0.098*
H13B	0.7785	0.5222	0.4602	0.098*
H13C	0.8829	0.4314	0.4150	0.098*
C14	0.9815 (6)	0.1934 (3)	0.3611 (2)	0.0505 (10)
H14A	0.9584	0.2332	0.4065	0.076*
H14B	1.0930	0.2235	0.3324	0.076*
H14C	1.0166	0.1236	0.3748	0.076*
C15	0.7238 (8)	0.2886 (4)	0.0750 (2)	0.0639 (13)
H15A	0.6026	0.3280	0.0625	0.096*
H15B	0.6875	0.2169	0.0800	0.096*
H15C	0.8247	0.2964	0.0352	0.096*
O1	0.5287 (5)	0.4215 (2)	0.20694 (18)	0.0571 (8)
H1	0.6020	0.4649	0.1860	0.086*
O2	0.8668 (5)	0.4339 (2)	0.13613 (17)	0.0552 (8)
H2	0.9526	0.4530	0.1676	0.083*
O3	0.8466 (4)	0.01860 (19)	0.26237 (18)	0.0514 (8)
H3	0.7350	−0.0110	0.2669	0.077*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0374 (19)	0.0289 (18)	0.052 (2)	−0.0012 (15)	−0.0026 (17)	0.0012 (16)
C2	0.047 (2)	0.0355 (19)	0.057 (2)	−0.0028 (17)	0.0002 (19)	0.0069 (19)
C3	0.052 (2)	0.040 (2)	0.054 (2)	−0.0037 (19)	0.006 (2)	0.0045 (18)
C4	0.0363 (18)	0.0366 (19)	0.052 (2)	0.0022 (16)	0.0005 (17)	0.0038 (17)
C5	0.0295 (17)	0.0314 (18)	0.051 (2)	−0.0034 (15)	−0.0017 (16)	0.0007 (16)
C6	0.0420 (19)	0.0282 (18)	0.054 (2)	0.0003 (16)	−0.0043 (17)	0.0016 (17)
C7	0.051 (2)	0.034 (2)	0.051 (2)	−0.0061 (17)	0.0018 (19)	0.0005 (17)
C8	0.046 (2)	0.043 (2)	0.062 (2)	−0.0048 (18)	0.007 (2)	0.0006 (19)
C9	0.047 (2)	0.039 (2)	0.064 (3)	0.0015 (18)	0.003 (2)	−0.0049 (19)
C10	0.039 (2)	0.0286 (17)	0.060 (2)	0.0001 (15)	−0.0035 (19)	−0.0002 (17)
C11	0.057 (2)	0.034 (2)	0.054 (2)	0.0072 (18)	0.006 (2)	0.0025 (17)
C12	0.076 (3)	0.060 (3)	0.074 (3)	0.021 (3)	0.017 (3)	−0.003 (3)
C13	0.075 (3)	0.050 (3)	0.071 (3)	−0.010 (2)	−0.004 (3)	−0.015 (2)
C14	0.050 (2)	0.038 (2)	0.063 (3)	0.0055 (18)	−0.011 (2)	0.0007 (19)
C15	0.077 (3)	0.060 (3)	0.055 (3)	−0.010 (2)	−0.007 (2)	−0.006 (2)
O1	0.0601 (18)	0.0451 (16)	0.066 (2)	0.0151 (14)	0.0018 (16)	0.0118 (14)
O2	0.0659 (19)	0.0384 (15)	0.0613 (19)	−0.0081 (14)	0.0002 (16)	0.0068 (14)
O3	0.0474 (15)	0.0297 (13)	0.077 (2)	0.0022 (12)	−0.0027 (16)	0.0018 (13)

Geometric parameters (Å, º) top

C1—C10	1.538 (5)	C9—C10	1.517 (5)
C1—C14	1.538 (5)	C9—H9A	0.9700
C1—C2	1.542 (5)	C9—H9B	0.9700
C1—C5	1.586 (5)	C10—O3	1.441 (4)
C2—C3	1.511 (5)	C10—H10	0.9800
C2—H2A	0.9700	C11—C13	1.522 (5)
C2—H2B	0.9700	C11—C12	1.523 (5)
C3—C4	1.541 (5)	C11—H11	0.9800
C3—H3A	0.9700	C12—H12A	0.9600
C3—H3B	0.9700	C12—H12B	0.9600
C4—C11	1.540 (5)	C12—H12C	0.9600
C4—C5	1.553 (5)	C13—H13A	0.9600
C4—H4	0.9800	C13—H13B	0.9600
C5—C6	1.532 (5)	C13—H13C	0.9600
C5—H5	0.9800	C14—H14A	0.9600
C6—O1	1.434 (4)	C14—H14B	0.9600
C6—C7	1.574 (5)	C14—H14C	0.9600
C6—H6	0.9800	C15—H15A	0.9600
C7—O2	1.439 (4)	C15—H15B	0.9600
C7—C15	1.524 (6)	C15—H15C	0.9600
C7—C8	1.525 (5)	O1—H1	0.8200
C8—C9	1.527 (5)	O2—H2	0.8200
C8—H8A	0.9700	O3—H3	0.8200
C8—H8B	0.9700

C10—C1—C14	110.7 (3)	H8A—C8—H8B	107.3
C10—C1—C2	110.0 (3)	C10—C9—C8	115.0 (3)
C14—C1—C2	110.1 (3)	C10—C9—H9A	108.5
C10—C1—C5	114.6 (3)	C8—C9—H9A	108.5
C14—C1—C5	109.3 (3)	C10—C9—H9B	108.5
C2—C1—C5	101.8 (3)	C8—C9—H9B	108.5
C3—C2—C1	105.3 (3)	H9A—C9—H9B	107.5
C3—C2—H2A	110.7	O3—C10—C9	106.0 (3)
C1—C2—H2A	110.7	O3—C10—C1	110.8 (3)
C3—C2—H2B	110.7	C9—C10—C1	115.7 (3)
C1—C2—H2B	110.7	O3—C10—H10	108.0
H2A—C2—H2B	108.8	C9—C10—H10	108.0
C2—C3—C4	103.0 (3)	C1—C10—H10	108.0
C2—C3—H3A	111.2	C13—C11—C12	110.7 (4)
C4—C3—H3A	111.2	C13—C11—C4	113.9 (3)
C2—C3—H3B	111.2	C12—C11—C4	110.6 (3)
C4—C3—H3B	111.2	C13—C11—H11	107.1
H3A—C3—H3B	109.1	C12—C11—H11	107.1
C11—C4—C3	114.5 (3)	C4—C11—H11	107.1
C11—C4—C5	115.8 (3)	C11—C12—H12A	109.5
C3—C4—C5	106.0 (3)	C11—C12—H12B	109.5
C11—C4—H4	106.6	H12A—C12—H12B	109.5
C3—C4—H4	106.6	C11—C12—H12C	109.5
C5—C4—H4	106.6	H12A—C12—H12C	109.5
C6—C5—C4	111.1 (3)	H12B—C12—H12C	109.5
C6—C5—C1	113.9 (3)	C11—C13—H13A	109.5
C4—C5—C1	106.2 (3)	C11—C13—H13B	109.5
C6—C5—H5	108.5	H13A—C13—H13B	109.5
C4—C5—H5	108.5	C11—C13—H13C	109.5
C1—C5—H5	108.5	H13A—C13—H13C	109.5
O1—C6—C5	110.9 (3)	H13B—C13—H13C	109.5
O1—C6—C7	107.1 (3)	C1—C14—H14A	109.5
C5—C6—C7	114.9 (3)	C1—C14—H14B	109.5
O1—C6—H6	107.9	H14A—C14—H14B	109.5
C5—C6—H6	107.9	C1—C14—H14C	109.5
C7—C6—H6	107.9	H14A—C14—H14C	109.5
O2—C7—C15	105.0 (3)	H14B—C14—H14C	109.5
O2—C7—C8	108.2 (3)	C7—C15—H15A	109.5
C15—C7—C8	112.2 (4)	C7—C15—H15B	109.5
O2—C7—C6	107.6 (3)	H15A—C15—H15B	109.5
C15—C7—C6	109.1 (3)	C7—C15—H15C	109.5
C8—C7—C6	114.2 (3)	H15A—C15—H15C	109.5
C7—C8—C9	117.2 (3)	H15B—C15—H15C	109.5
C7—C8—H8A	108.0	C6—O1—H1	109.5
C9—C8—H8A	108.0	C7—O2—H2	109.5
C7—C8—H8B	108.0	C10—O3—H3	109.5
C9—C8—H8B	108.0

C10—C1—C2—C3	−159.9 (3)	C5—C6—C7—O2	−96.0 (4)
C14—C1—C2—C3	77.8 (4)	O1—C6—C7—C15	−85.8 (4)
C5—C1—C2—C3	−38.0 (4)	C5—C6—C7—C15	150.6 (3)
C1—C2—C3—C4	42.7 (4)	O1—C6—C7—C8	147.8 (3)
C2—C3—C4—C11	−158.5 (3)	C5—C6—C7—C8	24.2 (4)
C2—C3—C4—C5	−29.5 (4)	O2—C7—C8—C9	−179.3 (3)
C11—C4—C5—C6	−101.2 (4)	C15—C7—C8—C9	−63.9 (5)
C3—C4—C5—C6	130.6 (3)	C6—C7—C8—C9	60.9 (5)
C11—C4—C5—C1	134.4 (3)	C7—C8—C9—C10	−46.9 (5)
C3—C4—C5—C1	6.2 (4)	C8—C9—C10—O3	−168.0 (3)
C10—C1—C5—C6	14.8 (4)	C8—C9—C10—C1	−44.8 (5)
C14—C1—C5—C6	139.7 (3)	C14—C1—C10—O3	63.0 (4)
C2—C1—C5—C6	−103.8 (3)	C2—C1—C10—O3	−58.9 (4)
C10—C1—C5—C4	137.5 (3)	C5—C1—C10—O3	−172.9 (3)
C14—C1—C5—C4	−97.6 (3)	C14—C1—C10—C9	−57.6 (4)
C2—C1—C5—C4	18.8 (4)	C2—C1—C10—C9	−179.5 (3)
C4—C5—C6—O1	43.4 (4)	C5—C1—C10—C9	66.5 (4)
C1—C5—C6—O1	163.3 (3)	C3—C4—C11—C13	58.4 (4)
C4—C5—C6—C7	165.0 (3)	C5—C4—C11—C13	−65.4 (4)
C1—C5—C6—C7	−75.0 (4)	C3—C4—C11—C12	−67.0 (4)
O1—C6—C7—O2	27.6 (4)	C5—C4—C11—C12	169.2 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O1ⁱ	0.82	1.97	2.783 (4)	172
O2—H2···O3ⁱⁱ	0.82	1.98	2.791 (4)	172
O1—H1···O2	0.82	1.96	2.518 (4)	124

Symmetry codes: (i) −x+1, y−1/2, −z+1/2; (ii) −x+2, y+1/2, −z+1/2.

¹H and ¹³C NMR data for compounds (1), (2) and (3) (δ in ppm and J in Hz)^a top

Position	(1)		(2)^b		(3)
δ(H)	δ(C)	δ(H)	δ(C)	δ(H)	δ(C)
1		47.8		49.7	3.79 (dd) (11.6, 4.4)	72.4
2	1.64 m; 1.41 m	39.6	1.61 m	40.7	1.90 m; 1.46 m	27.2
3	1.57 m; 1.37 m	23.6	1.69 m; 1.36 m	27.3	2.04 m; 1.39 m	35.5
4	2.03 m	50.6	1.88 m	51.2		74.0
5	1.60 overlapped	50.8	2.02 dd (7.8, 0.9)	49.0		76.7
6	3.27 d (11.4)	75.6	3.44 d (5.7)	82.2	1.72 t (12.9); 1.53 m	29.9
7		73.0		72.9	1.62 m	37.8
8	1.83 m; 1.56 m	33.9	1.98 dt (13.5, 3.1); 1.41 m	36.1	1.46 m; 1.28 m	23.4
9	1.79 m; 1.63 m	28.7	2.15 m; 1.31 m	29.3	1.78 dt (4.2, 13.3); 1.54 m	32.6
10	3.54 dd (10.2, 6.0)	74.5	4.04 d (10.3)	77.0		42.0
11	1.80 m	31.6	1.57 m	33.0	1.44 m	33.1
12	0.87 d (6.6)	21.7	0.87 d (6.7)	19.1	0.89 d (6.8)	19.1
13	0.93 d (6.6)	16.6	0.94 d (6.7)	22.0	0.89 d (6.8)	19.5
14	0.94 s	18.8	0.94 s	20.3	1.16 s	14.9
15	1.22 s	25.3	1.23 s	30.6	1.15 s	25.0
6-OH			3.92 d (5.7)

Notes: (a) data were measured in MeOH-d₄ at 600 MHz for (1), in acetone–d₆ at 500 MHz for (2) and (3); (b) C-9 of (2) was overlapped by signals of solvent, and data was obtained from the correlation in HMBC spectrum.

TNO production inhibitory activity of (1), (2) and (3) presented as IC₅₀ (µM) top

Compound	IC₅₀ (µM)	Compound	IC₅₀ (µM)
(1)	5.7±0.22	(3)	>50
(2)	>50	Dexamethasone	0.13±0.06

Subscribe to Acta Crystallographica Section C: Structural Chemistry

Buy online

You may purchase this article in PDF and/or HTML formats. For purchasers in the European Community who do not have a VAT number, VAT will be added at the local rate. Payments to the IUCr are handled by WorldPay, who will accept payment by credit card in several currencies. To purchase the article, please complete the form below (fields marked * are required), and then click on `Continue'.

E-mail address*
Repeat e-mail address* (for error checking)

Format*	PDF (US $40)
	HTML (US $40)
	PDF+HTML (US $50)
In order for VAT to be shown for your country javascript needs to be enabled.

VAT number (non-UK EC countries only)
Country*

Terms and conditions of use
Contact us

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Text
		Plain Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Text
		Plain Text

Search IUCr Journals		doi		Advanced search
Author		volume	page