Tylophorine B benzene solvate

The crystal structure of tylophorine B (or 2,3,6-tri­methoxy­phen­an­thro­[9,10-f]­indol­izidine) as the benzene solvate, C₂₃H₂₅NO₃·­C₆H₆, has been determined. The compound was isolated from albizzia julibrissin and this is the first definitive report of the steochemistry of tylo­phorine.

S1. Comment

Phenanthroindolizidine (tylophorine) and autofine have been reported to have antitumor and antibiotic effects. We have, for the first time, isolated tylophorine B from albizzia julibrissin in a search for interesting bioactive drugs. The title compound, (I), was extracted from the dried bark of silk trees which grow widely in the northwest of China. In traditional Chinese medicine, tylophorine B is used for pain relief, invigorating the circulation of the blood, treating insomnia and asthma, and the removal of strains. The flowers of silk trees are used to make tea by country folk to treat sore throat.

The MS—IR and NMR data suggest that the structure is consistent with that reported by Li et al. (1989). Although the molecular formulae of some similar and closely related compounds have also been reported (Cave et al., 1989; Mitra et al., 1996; Wadhawan & Sikka, 1976), the three-dimensional structure of tylophorine has not been determined until now.

The structure of tylophorine B (Fig. 1) shows a conjunction of phenanthro and indolizidine moieties. The aromatic rings lie almost in the same plane, with dihedral angles of only 1.7 (2) (A/B), 2.8 (2) (B/C) and 2.2 (2)° (A/C). The observed bond lengths and angles are normal in their alternate single- and double-bond display. The D ring, consisting of atoms C19, C20, C13 and C14, forms a plane with N1 above [0.338 (10) Å] and C15 below [0.325 (12) Å]. The B ring is almost coplanar with ring D. The E ring takes an envelope conformation and makes a dihedral angle of 6.7 (3)° with ring D. The dihedral angle between the B and D rings is 7.3 (2)°.

The benzene molecules are held very loosely in the crystal structure with apparently no strong hydrogen-bond interactions.

S2. Experimental

The dry bark of albizzia julibrissin (2.3 kg) was powdered and extracted with EtOH (333–343 K) at room temperature. The extract was concentrated and then developed repeatedly by silica-gel chromatography using EtOAc as the developing solvent to yield tylophorine and a number of other known compounds. The dried tylophorine powder is yellow and crystallization in commonly used solvents is difficult. The sample used in this study was recrystallized from a benzene/acetone solution (2:8).

S3. Refinement

The intensities of higher θ angle reflections were very weak due to both the large thermal motion of benzene and the poor crystal quality. This is also reflected in the R value obtained using all the data. The benzene solvent was treated as a fixed planar hexagon with individual isotropic displacement parameters for the C atoms. Attempts to use anisotropic displacement parameters did not result in a chemically realistic model. The absolute configuration was based on related chemistry.

Computing details

Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: MolEN/PC (Fair, 1990); program(s) used to solve structure: SHELXS86 (Sheldrick, 1985); program(s) used to refine structure: SHELXL93 (Sheldrick, 1993); molecular graphics: SHELXTL/PC (Siemens, 1995).

Figures

Fig. 1. A view of tylophorine B showing the labelling of the non-H atoms. Displacement ellipsoids are shown at 50% probability levels and H atoms are drawn as small circles of arbitrary radii.

2,3,6 trimethoxy phenanthro [9,10:6',7'] indolizedine

Crystal data

C23H25NO3·C6H6	Z = 1
Mr = 441.55	F(000) = 236
Triclinic, P1	Dx = 1.273 Mg m^−3
a = 5.393 (1) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.130 (2) Å	Cell parameters from 25 reflections
c = 11.963 (2) Å	θ = 10–20°
α = 92.67 (3)°	µ = 0.08 mm^−1
β = 95.02 (3)°	T = 293 K
γ = 100.45 (3)°	Block, pale yellow
V = 575.8 (2) Å^3	0.5 × 0.4 × 0.3 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	θmax = 27.8°, θmin = 1.7°
Radiation source: fine-focus sealed tube	h = 0→6
Graphite monochromator	k = −11→11
θ/2θ scans	l = −14→14
2510 measured reflections	3 standard reflections every 60 min
2510 independent reflections	intensity decay: <0.1%
1992 reflections with I > 2σ(I)

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.062	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.193	H-atom parameters constrained
S = 1.13	Calculated w = 1/[σ^2(Fo^2) + (0.1522P)^2 + 0.0106P] where P = (Fo^2 + 2Fc^2)/3
2510 reflections	(Δ/σ)max = 0.028
281 parameters	Δρmax = 0.48 e Å^−3
3 restraints	Δρmin = −0.36 e Å^−3

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	0.0884 (6)	0.9618 (4)	0.2243 (2)	0.0576 (8)
O2	−0.3198 (6)	0.8107 (3)	0.1176 (2)	0.0537 (8)
O3	−0.4947 (6)	0.8094 (4)	−0.4897 (3)	0.0570 (8)
N1	0.6663 (6)	1.4005 (3)	−0.2286 (3)	0.0389 (7)
C1	0.1242 (6)	1.0782 (4)	−0.3012 (3)	0.0361 (8)
C2	0.0864 (7)	1.0732 (5)	−0.4199 (3)	0.0440 (9)
H2	0.2087	1.1382	−0.4733	0.042 (11)*
C3	−0.1181 (8)	0.9848 (5)	−0.4798 (3)	0.0484 (10)
H3	−0.1238	0.9707	−0.5563	0.037 (10)*
C4	−0.2998 (7)	0.8934 (4)	−0.4224 (3)	0.0425 (9)
C5	−0.2660 (7)	0.8914 (4)	−0.3081 (3)	0.0413 (9)
H5	−0.3754	0.8328	−0.2787	0.028 (9)*
C6	−0.0535 (7)	0.9817 (4)	−0.2456 (3)	0.0343 (8)
C7	−0.0160 (6)	0.9817 (4)	−0.1238 (3)	0.0361 (8)
C8	−0.1953 (7)	0.8936 (4)	−0.0623 (3)	0.0386 (9)
H8	−0.3342	0.8323	−0.1118	0.056 (13)*
C9	−0.1579 (7)	0.8929 (4)	0.0520 (3)	0.0413 (9)
C10	0.0664 (7)	0.9794 (4)	0.1118 (3)	0.0391 (9)
C11	0.2314 (7)	1.0672 (4)	0.0527 (3)	0.0402 (9)
H11	0.3717	1.1390	0.1093	0.078 (17)*
C12	0.1976 (6)	1.0718 (4)	−0.0656 (3)	0.0341 (8)
C13	0.3750 (7)	1.1698 (4)	−0.1244 (3)	0.0356 (8)
C14	0.6031 (7)	1.2683 (4)	−0.0584 (3)	0.0376 (8)
H14B	0.5432	1.3594	−0.0003	0.041 (10)*
H14A	0.6682	1.2207	−0.0003	0.044 (11)*
C15	0.7922 (6)	1.3379 (4)	−0.1342 (3)	0.0380 (8)
H15	0.8994	1.2683	−0.1574	0.090 (19)*
C16	0.9925 (7)	1.4726 (4)	−0.0826 (4)	0.0468 (10)
H16B	0.9165	1.5272	−0.0291	0.031 (9)*
H16A	1.1255	1.4159	−0.0291	0.068 (14)*
C17	1.0685 (8)	1.5581 (5)	−0.1848 (5)	0.0561 (11)
H17B	1.2515	1.5267	−0.1943	0.042 (10)*
H17A	1.0425	1.6654	−0.1670	0.083 (17)*
C18	0.8754 (8)	1.4872 (5)	−0.2824 (4)	0.0506 (10)
H18B	0.9556	1.4151	−0.3349	0.085 (18)*
H18A	0.8306	1.5538	−0.3349	0.048 (11)*
C19	0.5085 (7)	1.2830 (5)	−0.3023 (4)	0.0431 (9)
H19B	0.4175	1.3316	−0.3614	0.043 (10)*
H19A	0.5836	1.2203	−0.3614	0.069 (15)*
C20	0.3342 (6)	1.1751 (4)	−0.2383 (3)	0.0341 (8)
C21	0.3250 (10)	1.0213 (8)	0.2835 (4)	0.0719 (15)
H21C	0.4992	0.9707	0.2498	0.073 (15)*
H21B	0.3312	1.0273	0.3592	0.11 (2)*
H21A	0.3494	1.1252	0.2697	0.17 (5)*
C22	−0.5297 (9)	0.7136 (5)	0.0623 (4)	0.0580 (12)
H22C	−0.6232	0.7503	0.0002	0.09 (2)*
H22B	−0.4982	0.6390	0.0002	0.079 (17)*
H22A	−0.6293	0.6596	0.1133	0.13 (3)*
C23	−0.6888 (9)	0.7183 (6)	−0.4352 (5)	0.0604 (12)
H23C	−0.5871	0.6380	−0.3910	0.058 (13)*
H23B	−0.7961	0.7767	−0.3910	0.076 (17)*
H23A	−0.8371	0.6927	−0.4731	0.071 (16)*
C24	0.9273 (12)	0.3092 (5)	0.3246 (5)	0.120 (3)*
H24	0.9819	0.2183	0.3249	0.144*
C25	0.7650 (12)	0.3429 (6)	0.4021 (5)	0.102 (2)*
H25	0.7111	0.2745	0.4542	0.123*
C26	0.6834 (10)	0.4788 (6)	0.4017 (4)	0.108 (2)*
H26	0.5749	0.5014	0.4536	0.130*
C27	0.7640 (11)	0.5811 (5)	0.3239 (5)	0.108 (2)*
H27	0.7094	0.6720	0.3236	0.130*
C28	0.9263 (13)	0.5474 (6)	0.2464 (5)	0.128 (3)*
H28	0.9802	0.6158	0.1943	0.153*
C29	1.0079 (12)	0.4115 (7)	0.2468 (5)	0.134 (3)*
H29	1.1165	0.3890	0.1949	0.160*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0506 (17)	0.0754 (19)	0.0402 (14)	−0.0072 (15)	0.0018 (13)	0.0164 (13)
O2	0.0478 (17)	0.0615 (18)	0.0478 (15)	−0.0077 (14)	0.0129 (13)	0.0175 (13)
O3	0.0468 (16)	0.067 (2)	0.0481 (15)	−0.0104 (14)	−0.0036 (13)	0.0069 (13)
N1	0.0283 (14)	0.0322 (14)	0.0572 (17)	0.0037 (11)	0.0082 (13)	0.0124 (12)
C1	0.0318 (19)	0.0352 (17)	0.0423 (19)	0.0054 (15)	0.0092 (15)	0.0069 (14)
C2	0.041 (2)	0.050 (2)	0.0407 (19)	0.0034 (17)	0.0096 (16)	0.0051 (15)
C3	0.054 (2)	0.052 (2)	0.0355 (17)	−0.0023 (19)	0.0069 (17)	0.0083 (16)
C4	0.037 (2)	0.045 (2)	0.0429 (19)	0.0034 (17)	0.0010 (16)	0.0004 (16)
C5	0.039 (2)	0.0389 (19)	0.0445 (19)	−0.0011 (17)	0.0075 (16)	0.0108 (15)
C6	0.0315 (18)	0.0331 (17)	0.0382 (16)	0.0055 (14)	0.0040 (14)	0.0026 (13)
C7	0.0323 (19)	0.0339 (18)	0.0443 (19)	0.0069 (15)	0.0095 (16)	0.0130 (14)
C8	0.0343 (19)	0.0356 (18)	0.044 (2)	0.0003 (16)	0.0074 (16)	0.0066 (15)
C9	0.038 (2)	0.0362 (18)	0.049 (2)	−0.0008 (16)	0.0136 (17)	0.0107 (15)
C10	0.0331 (18)	0.045 (2)	0.0379 (18)	0.0035 (16)	0.0001 (15)	0.0062 (15)
C11	0.0335 (19)	0.0397 (19)	0.0430 (19)	−0.0029 (16)	0.0002 (16)	0.0029 (15)
C12	0.0265 (17)	0.0343 (17)	0.0412 (18)	0.0056 (15)	0.0012 (15)	0.0034 (14)
C13	0.0320 (19)	0.0300 (16)	0.0451 (19)	0.0043 (15)	0.0072 (15)	0.0056 (14)
C14	0.0267 (17)	0.0415 (18)	0.0427 (19)	0.0016 (15)	0.0005 (15)	0.0064 (14)
C15	0.0274 (17)	0.0333 (16)	0.0515 (19)	0.0010 (14)	0.0028 (15)	0.0050 (14)
C16	0.0281 (17)	0.0402 (19)	0.067 (2)	−0.0067 (15)	0.0026 (17)	0.0060 (18)
C17	0.041 (2)	0.041 (2)	0.085 (3)	−0.0027 (17)	0.015 (2)	0.014 (2)
C18	0.041 (2)	0.045 (2)	0.063 (2)	−0.0044 (18)	0.0109 (18)	0.0150 (18)
C19	0.0353 (19)	0.046 (2)	0.0479 (19)	0.0009 (16)	0.0121 (16)	0.0124 (15)
C20	0.0259 (16)	0.0310 (16)	0.0445 (18)	0.0015 (14)	0.0062 (14)	0.0039 (14)
C21	0.062 (3)	0.104 (4)	0.043 (2)	0.001 (3)	−0.003 (2)	0.002 (2)
C22	0.049 (2)	0.054 (2)	0.066 (3)	−0.013 (2)	0.015 (2)	0.016 (2)
C23	0.042 (2)	0.058 (2)	0.071 (3)	−0.013 (2)	−0.004 (2)	0.004 (2)

Geometric parameters (Å, º)

O1—C10	1.361 (5)	C8—C9	1.365 (6)
O1—C21	1.407 (5)	C9—C10	1.431 (5)
O2—C9	1.370 (4)	C10—C11	1.356 (6)
O2—C22	1.399 (5)	C11—C12	1.415 (5)
O3—C4	1.357 (5)	C12—C13	1.441 (5)
O3—C23	1.437 (5)	C13—C20	1.366 (5)
N1—C19	1.450 (5)	C13—C14	1.520 (5)
N1—C15	1.459 (5)	C14—C15	1.499 (5)
N1—C18	1.470 (5)	C15—C16	1.547 (5)
C1—C6	1.414 (5)	C16—C17	1.528 (6)
C1—C2	1.414 (5)	C17—C18	1.529 (7)
C1—C20	1.434 (5)	C19—C20	1.516 (5)
C2—C3	1.366 (6)	C24—C25	1.3900
C3—C4	1.415 (5)	C24—C29	1.3900
C4—C5	1.364 (6)	C25—C26	1.3900
C5—C6	1.415 (5)	C26—C27	1.3900
C6—C7	1.453 (5)	C27—C28	1.3900
C7—C12	1.397 (5)	C28—C29	1.3900
C7—C8	1.422 (5)
C10—O1—C21	116.6 (3)	C11—C10—C9	118.3 (3)
C9—O2—C22	117.2 (3)	O1—C10—C9	114.4 (3)
C4—O3—C23	117.1 (3)	C10—C11—C12	123.0 (3)
C19—N1—C15	110.7 (3)	C7—C12—C11	118.3 (3)
C19—N1—C18	113.8 (3)	C7—C12—C13	120.7 (3)
C15—N1—C18	104.2 (3)	C11—C12—C13	121.0 (3)
C6—C1—C2	117.2 (3)	C20—C13—C12	119.8 (3)
C6—C1—C20	120.5 (3)	C20—C13—C14	120.7 (3)
C2—C1—C20	122.3 (3)	C12—C13—C14	119.4 (3)
C3—C2—C1	122.4 (4)	C15—C14—C13	111.7 (3)
C2—C3—C4	119.6 (3)	N1—C15—C14	110.7 (3)
O3—C4—C5	125.3 (4)	N1—C15—C16	102.7 (3)
O3—C4—C3	114.9 (3)	C14—C15—C16	116.5 (3)
C5—C4—C3	119.8 (3)	C17—C16—C15	103.3 (3)
C4—C5—C6	120.9 (3)	C16—C17—C18	105.5 (3)
C5—C6—C1	120.0 (3)	N1—C18—C17	104.8 (3)
C5—C6—C7	121.6 (3)	N1—C19—C20	112.2 (3)
C1—C6—C7	118.4 (3)	C13—C20—C1	120.8 (3)
C12—C7—C8	119.2 (3)	C13—C20—C19	121.3 (3)
C12—C7—C6	119.6 (3)	C1—C20—C19	117.9 (3)
C8—C7—C6	121.2 (3)	C25—C24—C29	120.0
C9—C8—C7	121.0 (3)	C26—C25—C24	120.0
O2—C9—C8	124.8 (4)	C27—C26—C25	120.0
O2—C9—C10	115.0 (3)	C26—C27—C28	120.0
C8—C9—C10	120.2 (3)	C29—C28—C27	120.0
C11—C10—O1	127.4 (3)	C28—C29—C24	120.0