Cheilanthifoline

The title compound, 6,6a,11,14-tetra­hydro-8-hydr­oxy-9-meth­oxy-12H-benzo[a]-1,3-benzodioxolo[4,5-g]quinolizine, C₁₉H₁₉NO₄, a protoberberine-type alkaloid, was isolated from the roots of the plant Sinomenium acutum. Both the piperidine rings adopt half-chair conformations. The mol­ecules exist in a dimeric form through O—H...O hydrogen bonding between the hydr­oxy group and meth­oxy O atom.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.036
• wR factor = 0.089
• Data-to-parameter ratio = 7.5

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) .....       7.48

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           25.50
           From the CIF: _reflns_number_total               1669
           Count of symmetry unique reflns         1670
           Completeness (_total/calc)             99.94%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   1 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion

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S1. Comment

Sinomenium acutum is distributed mainly in hilly regions of southwest, northwest and southeast China. The roots and stems of the plant are used as folk medicine to cure rheumatism, dropsy and dermatophytosis. A number of alkaloids with different kinds of skeletons have been isolated from the plant (Jiangsu New Medical College, 1985; Chen et al., 1991; Moriyasu et al., 1993, 1994). In the course of our systematic search for bioactive substances from Chinese traditional herb medicines, we have studied the roots of S. acutum and obtained the title compound, (I). Compound (I) was first isolated in some species of Corydalis and identified on the basis of its mass and its NMR, IR and UV spectra (Blask et al., 1981; Haisov & Slavk, 1973). We report here the crystal structure of (I).

The benzo[1,3]dioxole ring system is essentially planar (Fig. 1). Both the piperidine rings adopt half-chair conformations. The methoxy group attached at atom C3 is twisted away from the benzene ring with a torsion angle C20—O4—C3—C4 of 25.2 (4)°. In the crystal packing, intermolecular hydrogen bonding between the hydroxy group and the methoxy O atom of an adjacent molecule leads to the formation of dimers (Fig. 2). In addition, a C—H···π interaction is observed (Table 1).

S2. Experimental

Sinomenine is produced from the powder of the roots of S. acutum by the Baoji Yongjia Plant Medicine Extracting Limited Company, Baoji, People's Republic of China. It is obtained from the benzene extract of the powder in a vacuum (Chen et al., 1995). The remaining benzene mother liquor (3 kg), after the extraction of sinomenine, was obtained from the company. It was subjected to repeated chromatography on a silica gel column, and eluted with petroleum ether/acetone (from 20:1 to 3:1) to afford compound (I) (0.2 g). Single crystals of (I) were obtained after repeated recrystallization from acetone.

S3. Refinement

The hydroxy H atom was located in a difference Fourier map and refined freely. The other H atoms were placed in idealized positions and constrained to ride on their parent atoms, with C—H distances in the range 0.93–0.98 Å, and with U_iso(H) = 1.2U_eq(C). In the absence of significant anomalous scattering, Friedel pairs were merged prior to the final refinement.

Computing details

Data collection: XSCANS (Siemens, 1994); cell refinement: XSCANS; data reduction: SHELXTL (Sheldrick, 1997b); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997a); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997a); molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. The structure of (I), showing 40% probability displacement ellipsoids and the atom-numbering scheme.
	Fig. 2. The crystal packing of (I), showing O—H···O hydrogen-bonded (dashed lines) dimers. H atoms not involved in the interactions shown have been omitted.

6,6a,11,14-Tetrahydro-8-hydroxy-9-methoxy-12H-benzo[a]- 1,3-benzodioxolo[4,5-g]quinolizine

Crystal data

C19H19NO4	F(000) = 688
Mr = 325.35	Dx = 1.358 Mg m^−3
Monoclinic, C2	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C 2y	Cell parameters from 39 reflections
a = 13.314 (2) Å	θ = 2.6–11.5°
b = 5.151 (1) Å	µ = 0.10 mm^−1
c = 23.585 (3) Å	T = 296 K
β = 100.39 (1)°	Rhombohedron, yellow
V = 1590.9 (4) Å^3	0.48 × 0.34 × 0.14 mm
Z = 4

Data collection

Siemens P4 diffractometer	Rint = 0.013
Radiation source: normal-focus sealed tube	θmax = 25.5°, θmin = 1.8°
Graphite monochromator	h = 0→16
ω scans	k = 0→6
1816 measured reflections	l = −28→28
1669 independent reflections	3 standard reflections every 97 reflections
1331 reflections with I > 2σ(I)	intensity decay: 3.9%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.036	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.089	w = 1/[σ^2(Fo^2) + (0.051P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.99	(Δ/σ)max = 0.001
1669 reflections	Δρmax = 0.14 e Å^−3
223 parameters	Δρmin = −0.14 e Å^−3
1 restraint	Extinction correction: SHELXTL, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0144 (14)

Special details

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

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.82863 (15)	1.3199 (5)	0.40355 (8)	0.0684 (8)
O2	0.70057 (17)	1.4199 (5)	0.45455 (8)	0.0682 (7)
O3	0.45140 (13)	0.3567 (5)	0.07211 (8)	0.0537 (6)
O4	0.60253 (14)	0.0927 (4)	0.03625 (7)	0.0509 (6)
N7	0.79074 (14)	0.7517 (5)	0.26188 (8)	0.0368 (5)
C1	0.56992 (19)	0.5446 (6)	0.14804 (10)	0.0406 (7)
H1	0.5160	0.6316	0.1598	0.049*
C2	0.54997 (18)	0.3825 (6)	0.10126 (10)	0.0388 (7)
C3	0.63021 (19)	0.2486 (6)	0.08397 (9)	0.0377 (7)
C4	0.72871 (18)	0.2873 (6)	0.11289 (10)	0.0376 (6)
H4	0.7823	0.1991	0.1011	0.045*
C5	0.85767 (18)	0.5095 (6)	0.18788 (11)	0.0388 (7)
H5A	0.8997	0.5252	0.1585	0.047*
H5B	0.8831	0.3646	0.2126	0.047*
C6	0.86563 (18)	0.7558 (6)	0.22322 (11)	0.0414 (7)
H6A	0.9339	0.7713	0.2457	0.050*
H6B	0.8532	0.9049	0.1978	0.050*
C8	0.8125 (2)	0.9656 (7)	0.30289 (11)	0.0477 (8)
H8A	0.8225	1.1232	0.2821	0.057*
H8B	0.8755	0.9292	0.3294	0.057*
C9	0.7416 (2)	1.1829 (7)	0.38215 (10)	0.0457 (8)
C10	0.6660 (2)	1.2426 (7)	0.41200 (10)	0.0503 (8)
C11	0.5717 (2)	1.1338 (8)	0.39869 (11)	0.0596 (10)
H11	0.5200	1.1757	0.4188	0.072*
C12	0.5563 (2)	0.9556 (8)	0.35317 (11)	0.0573 (9)
H12	0.4928	0.8765	0.3431	0.069*
C13	0.61563 (17)	0.7075 (6)	0.27260 (10)	0.0424 (8)
H13A	0.5451	0.7188	0.2532	0.051*
H13B	0.6279	0.5315	0.2868	0.051*
C14	0.74894 (17)	0.4575 (5)	0.15967 (9)	0.0330 (6)
C15	0.66902 (18)	0.5829 (6)	0.17850 (9)	0.0341 (6)
C16	0.68580 (16)	0.7671 (6)	0.22975 (9)	0.0352 (6)
H16	0.6727	0.9449	0.2156	0.042*
C17	0.72891 (19)	1.0100 (6)	0.33682 (10)	0.0401 (7)
C18	0.63294 (18)	0.8930 (6)	0.32253 (9)	0.0410 (7)
C19	0.8035 (3)	1.4720 (9)	0.44975 (13)	0.0719 (11)
H19A	0.8486	1.4280	0.4855	0.086*
H19B	0.8118	1.6551	0.4421	0.086*
C20	0.6676 (2)	−0.1137 (6)	0.02803 (11)	0.0493 (7)
H20A	0.7265	−0.0468	0.0147	0.059*
H20B	0.6319	−0.2319	0.0000	0.059*
H20C	0.6889	−0.2034	0.0639	0.059*
H3O	0.443 (2)	0.248 (8)	0.0411 (14)	0.087 (12)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0617 (13)	0.093 (2)	0.0515 (11)	−0.0232 (15)	0.0136 (10)	−0.0308 (14)
O2	0.0771 (14)	0.0825 (19)	0.0477 (10)	−0.0066 (15)	0.0183 (10)	−0.0245 (13)
O3	0.0370 (10)	0.0749 (16)	0.0450 (11)	0.0030 (12)	−0.0038 (8)	−0.0146 (12)
O4	0.0563 (12)	0.0531 (13)	0.0387 (9)	0.0139 (11)	−0.0038 (9)	−0.0134 (11)
N7	0.0307 (11)	0.0462 (14)	0.0336 (10)	−0.0025 (11)	0.0058 (8)	−0.0058 (11)
C1	0.0348 (13)	0.0514 (19)	0.0360 (12)	0.0088 (14)	0.0076 (10)	−0.0018 (14)
C2	0.0335 (13)	0.0487 (18)	0.0330 (12)	0.0012 (14)	0.0023 (10)	−0.0017 (14)
C3	0.0449 (14)	0.0402 (17)	0.0275 (11)	0.0048 (14)	0.0051 (11)	0.0019 (13)
C4	0.0394 (14)	0.0369 (16)	0.0371 (13)	0.0075 (13)	0.0089 (11)	0.0044 (14)
C5	0.0326 (13)	0.0399 (17)	0.0450 (13)	0.0014 (13)	0.0096 (11)	0.0005 (14)
C6	0.0316 (13)	0.0470 (18)	0.0471 (14)	−0.0042 (14)	0.0108 (11)	0.0000 (15)
C8	0.0402 (14)	0.060 (2)	0.0433 (13)	−0.0069 (16)	0.0092 (12)	−0.0105 (17)
C9	0.0470 (16)	0.057 (2)	0.0333 (13)	−0.0073 (15)	0.0065 (12)	−0.0019 (15)
C10	0.0603 (18)	0.060 (2)	0.0309 (13)	−0.0045 (17)	0.0076 (13)	−0.0085 (16)
C11	0.0539 (18)	0.089 (3)	0.0399 (14)	0.007 (2)	0.0178 (13)	−0.0110 (18)
C12	0.0437 (15)	0.086 (3)	0.0437 (14)	−0.0083 (18)	0.0118 (12)	−0.0098 (18)
C13	0.0327 (13)	0.059 (2)	0.0354 (13)	−0.0049 (14)	0.0062 (11)	−0.0048 (15)
C14	0.0336 (12)	0.0323 (15)	0.0333 (12)	0.0046 (12)	0.0064 (10)	0.0061 (13)
C15	0.0354 (13)	0.0360 (15)	0.0307 (12)	0.0000 (13)	0.0054 (10)	−0.0006 (13)
C16	0.0317 (13)	0.0380 (16)	0.0353 (12)	0.0019 (13)	0.0047 (10)	−0.0002 (13)
C17	0.0400 (14)	0.0489 (17)	0.0313 (12)	−0.0009 (14)	0.0063 (10)	−0.0003 (14)
C18	0.0401 (14)	0.0525 (19)	0.0306 (12)	0.0003 (15)	0.0072 (10)	0.0009 (14)
C19	0.082 (2)	0.082 (3)	0.0537 (17)	−0.017 (2)	0.0199 (16)	−0.023 (2)
C20	0.0648 (18)	0.0365 (17)	0.0467 (15)	0.0039 (16)	0.0104 (13)	−0.0049 (15)

Geometric parameters (Å, º)

O1—C9	1.373 (3)	C8—C17	1.500 (3)
O1—C19	1.430 (4)	C8—H8A	0.97
O2—C10	1.373 (3)	C8—H8B	0.97
O2—C19	1.421 (4)	C9—C10	1.363 (4)
O3—C2	1.374 (3)	C9—C17	1.378 (4)
O3—H3O	0.91 (4)	C10—C11	1.360 (4)
O4—C3	1.378 (3)	C11—C12	1.399 (4)
O4—C20	1.407 (3)	C11—H11	0.93
N7—C8	1.461 (4)	C12—C18	1.391 (3)
N7—C16	1.467 (3)	C12—H12	0.93
N7—C6	1.468 (3)	C13—C18	1.501 (4)
C1—C2	1.371 (3)	C13—C16	1.526 (3)
C1—C15	1.398 (3)	C13—H13A	0.97
C1—H1	0.93	C13—H13B	0.97
C2—C3	1.393 (3)	C14—C15	1.385 (3)
C3—C4	1.379 (3)	C15—C16	1.521 (3)
C4—C14	1.397 (3)	C16—H16	0.98
C4—H4	0.93	C17—C18	1.398 (4)
C5—C14	1.504 (3)	C19—H19A	0.97
C5—C6	1.511 (4)	C19—H19B	0.97
C5—H5A	0.97	C20—H20A	0.96
C5—H5B	0.97	C20—H20B	0.96
C6—H6A	0.97	C20—H20C	0.96
C6—H6B	0.97
C9—O1—C19	105.3 (2)	C10—C11—C12	116.7 (3)
C10—O2—C19	105.6 (2)	C10—C11—H11	121.7
C2—O3—H3O	116 (2)	C12—C11—H11	121.7
C3—O4—C20	118.2 (2)	C18—C12—C11	122.1 (3)
C8—N7—C16	111.0 (2)	C18—C12—H12	119.0
C8—N7—C6	109.0 (2)	C11—C12—H12	119.0
C16—N7—C6	111.64 (18)	C18—C13—C16	111.5 (2)
C2—C1—C15	121.8 (2)	C18—C13—H13A	109.3
C2—C1—H1	119.1	C16—C13—H13A	109.3
C15—C1—H1	119.1	C18—C13—H13B	109.3
C1—C2—O3	119.4 (2)	C16—C13—H13B	109.3
C1—C2—C3	119.3 (2)	H13A—C13—H13B	108.0
O3—C2—C3	121.3 (2)	C15—C14—C4	119.8 (2)
O4—C3—C4	125.4 (2)	C15—C14—C5	120.6 (2)
O4—C3—C2	114.9 (2)	C4—C14—C5	119.6 (2)
C4—C3—C2	119.6 (2)	C14—C15—C1	118.6 (2)
C3—C4—C14	120.8 (2)	C14—C15—C16	122.3 (2)
C3—C4—H4	119.6	C1—C15—C16	119.1 (2)
C14—C4—H4	119.6	N7—C16—C15	111.5 (2)
C14—C5—C6	111.1 (2)	N7—C16—C13	106.67 (18)
C14—C5—H5A	109.4	C15—C16—C13	112.4 (2)
C6—C5—H5A	109.4	N7—C16—H16	108.7
C14—C5—H5B	109.4	C15—C16—H16	108.7
C6—C5—H5B	109.4	C13—C16—H16	108.7
H5A—C5—H5B	108.0	C9—C17—C18	116.4 (2)
N7—C6—C5	110.0 (2)	C9—C17—C8	120.9 (3)
N7—C6—H6A	109.7	C18—C17—C8	122.6 (2)
C5—C6—H6A	109.7	C12—C18—C17	119.9 (3)
N7—C6—H6B	109.7	C12—C18—C13	122.1 (2)
C5—C6—H6B	109.7	C17—C18—C13	117.9 (2)
H6A—C6—H6B	108.2	O2—C19—O1	108.6 (3)
N7—C8—C17	113.0 (2)	O2—C19—H19A	110.0
N7—C8—H8A	109.0	O1—C19—H19A	110.0
C17—C8—H8A	109.0	O2—C19—H19B	110.0
N7—C8—H8B	109.0	O1—C19—H19B	110.0
C17—C8—H8B	109.0	H19A—C19—H19B	108.4
H8A—C8—H8B	107.8	O4—C20—H20A	109.5
C10—C9—O1	110.3 (2)	O4—C20—H20B	109.5
C10—C9—C17	123.2 (3)	H20A—C20—H20B	109.5
O1—C9—C17	126.5 (2)	O4—C20—H20C	109.5
C11—C10—C9	121.7 (3)	H20A—C20—H20C	109.5
C11—C10—O2	128.1 (3)	H20B—C20—H20C	109.5
C9—C10—O2	110.3 (3)
C15—C1—C2—O3	−178.5 (3)	C5—C14—C15—C1	174.8 (3)
C15—C1—C2—C3	1.0 (4)	C4—C14—C15—C16	179.0 (2)
C20—O4—C3—C4	25.2 (4)	C5—C14—C15—C16	−3.0 (4)
C20—O4—C3—C2	−157.7 (2)	C2—C1—C15—C14	1.6 (4)
C1—C2—C3—O4	−179.4 (2)	C2—C1—C15—C16	179.5 (2)
O3—C2—C3—O4	0.1 (4)	C8—N7—C16—C15	167.7 (2)
C1—C2—C3—C4	−2.1 (4)	C6—N7—C16—C15	46.0 (3)
O3—C2—C3—C4	177.4 (2)	C8—N7—C16—C13	−69.2 (3)
O4—C3—C4—C14	177.6 (2)	C6—N7—C16—C13	169.1 (3)
C2—C3—C4—C14	0.6 (4)	C14—C15—C16—N7	−11.3 (3)
C8—N7—C6—C5	169.4 (2)	C1—C15—C16—N7	170.9 (2)
C16—N7—C6—C5	−67.7 (3)	C14—C15—C16—C13	−131.0 (3)
C14—C5—C6—N7	50.4 (3)	C1—C15—C16—C13	51.1 (3)
C16—N7—C8—C17	45.6 (3)	C18—C13—C16—N7	58.0 (3)
C6—N7—C8—C17	168.9 (2)	C18—C13—C16—C15	−179.5 (2)
C19—O1—C9—C10	0.3 (4)	C10—C9—C17—C18	−0.6 (4)
C19—O1—C9—C17	179.7 (3)	O1—C9—C17—C18	−179.9 (3)
O1—C9—C10—C11	179.4 (3)	C10—C9—C17—C8	175.7 (3)
C17—C9—C10—C11	−0.1 (5)	O1—C9—C17—C8	−3.7 (4)
O1—C9—C10—O2	−0.5 (4)	N7—C8—C17—C9	172.2 (3)
C17—C9—C10—O2	−179.9 (3)	N7—C8—C17—C18	−11.7 (4)
C19—O2—C10—C11	−179.4 (4)	C11—C12—C18—C17	−0.2 (5)
C19—O2—C10—C9	0.5 (4)	C11—C12—C18—C13	−178.2 (3)
C9—C10—C11—C12	0.6 (5)	C9—C17—C18—C12	0.7 (4)
O2—C10—C11—C12	−179.6 (3)	C8—C17—C18—C12	−175.5 (3)
C10—C11—C12—C18	−0.4 (5)	C9—C17—C18—C13	178.8 (2)
C3—C4—C14—C15	2.1 (4)	C8—C17—C18—C13	2.6 (4)
C3—C4—C14—C5	−175.9 (2)	C16—C13—C18—C12	152.2 (3)
C6—C5—C14—C15	−16.5 (3)	C16—C13—C18—C17	−25.9 (4)
C6—C5—C14—C4	161.5 (2)	C10—O2—C19—O1	−0.3 (4)
C4—C14—C15—C1	−3.1 (4)	C9—O1—C19—O2	0.0 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3O···O4	0.91 (4)	2.29 (3)	2.688 (3)	106 (2)
O3—H3O···O4^i	0.91 (4)	1.98 (4)	2.870 (3)	163 (3)
C20—H20C···Cg1^ii	0.96	2.62	3.460 (3)	146

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