Macrocalyxin I

The title compound, 2-[1,2,3,4,4a,4b,5,6,7,8,8a,9-dodeca­hydro-7-hydroxy-4b,8,8-tri­methyl­phenanthren-2-yl]­propenoic acid, C₂₀H₃₀O₃, is a naturally occurring diterpenoid which was isolated from Rabdosia macrocalyx. The hydroxy and carboxy groups, which are located at the two ends of the mol­ecule, both serve as simultaneous hydrogen-bond donors and acceptors. Two intermolecular O-H...O hydrogen bonds are present and link each mol­ecule to four neighbours, thus forming an extensive hydrogen-bond network within the crystal.

S1. Comment

Rabdosia macrocalyx is widely distributed in Anhui, Jiangsu,Zhejiang, Jiangxi, Fujian, Hunan, Guangdong, Guangxi and Taiwan provinces, China. It has been used as a folk medicine in China. Its decoctions are used as antibiotics and for antitumor treatment. Macrocalyxins A, B (Cheng et al., 1984), C (Wang et al., 1984), D (Wang et al., 1985), E (Wang et al., 1986), F, G and H (Wang et al., 1995) have been isolated previously from this plant. In order to isolate more bioactive constituents from this plant, we investigated the whole herb of Rabdosia macrocalyx, which led to the isolation of the title compound, the natural diterpenoid Macrocalyxin I, (1), which was isolated from Rabdosia macrocalyx Hara for the first time. Its structure was established from spectral evidence and was confirmed by this X-ray diffraction study.

The molecule of (1) (Fig. 1) is composed of three six-membered rings. Rings A (C1–C5/C10) and C (C8/C9/C12–C14) adopt a chair conformation, with mean torsion angles of 51.4 and 52.4°, respectively. Ring B (C5–C9/C10) adopts a half-chair conformation owing to the double bond between C7 and C8. The stereochemistry of the A/B ring junction is trans, and the dihedral angle between rings A and B is 17.6°; the dihedral angle between rings B and C is 14.9°. The configurations at the other chiral centers are as follows: C3—OH, C10—Me, C9—H and C13—H are axial and the 1-carboxylethenyl group is equatorial at C13.

The C17—C15—C16—O2 torsion angle has a vlaue of 172.4 (3)° because of the conjugated double bound. The best least-squares plane formed by atoms C17/C15/C16/O2/O3 has a maximum deviation of 0.0592 Å, and the dihedral angle between this plane and ring C is 114.2°. The hydroxyl group located at C3 and the carboxyl group located at C15 participate in hydrogen bonding. Both groups serve as simultaneous hydrogen-bond donors and acceptors. Two intermolecular O—H···O hydrogen bonds (Table 2) are present and link each molecule to four adjacent neighbours (Fig. 2). The overall result is an extended hydrogen-bonding network throughout the structure (Fig. 3).

S2. Experimental

Dried powder (7.5 kg) of the whole herb of Rabdosia macrocalyx were soaked three times with 95% EtOH at room temperature. The solvent was removed by evaporation at reduced pressure, the residue was successively fractioned with petroleum ether, EtOAc and n-BuOH. The residue of the EtOAc fraction was subjected to column chromatography over silica gel. The column was eluted with a petroleum ether–EtOAc mixture. The crude compound was purified by column chromatography on silica gel with an acetone–chloroform mixture, producing 210 mg of macrocalyxin A and 60 mg of the pure title compound, (1) [m.p.: 490.5–492.5 K (CHCl₃/CH₃COCH₃)]. ¹³C NMR (125 MHz, pyridine): δ (p.p.m.) 169.8 (C16), 147.5 (C15), 137.2 (C8), 121.7 (C17), 121.2 (C7), 75.1 (C3), 52.4 (C9), 44.3 (C5), 41.7 (C6), 39.7 (C13), 37.5 (C4), 35.3 (C10), 32.3 (C14), 32.2 (C12), 29.3 (C19), 26.4 (C11), 25.7 (C1), 23.3 (C2), 23.1 (C18), 15.3 (C20). Crystals suitable for X-ray structure analysis were obtained by slow evaporation from an aqueous solution solution in chloroform and methanol (1:1) at room temperature.

S3. Refinement

H atoms were placed in the geometrically calculated positions and included in the final refinement as riding, with U_iso values equal to 1.2U_eq of the carrier atom. An attempt to establish the absolute configuration failed. The Flack (1983) parameter obtained was -0.9 (16). The Friedel pairs were merged before the final refinement and only the relative stereochemistry is shown in the Scheme and Figures.

Computing details

Data collection: XSCANS (Siemens, 1994); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL/PC (Siemens, 1991); software used to prepare material for publication: SHELXTL/PC.

Figures

	Fig. 1. View of the title molecule showing the atomic numbering scheme and 50% probability displacement ellipsoids.
	Fig. 2. The intermoleculer hydrogen bonding in (1) viewed normal to the (001) plane. H atoms have been omitted for clarity, except for those involved in hydrogen bonds, which are drawn as small spheres of arbitrary radii. Hydrogen bonds are shown as dashed lines.
	Fig. 3. The crystal-packing diagram for the title compound viewed down the c axis. H atoms have been omitted for clarity, except for these involved in hydrogen bonds.

2-[1,2,3,4,4a,4 b,5,6,7,8,8a,9-dodecahydro-7-hydroxy-4 b,8,8-trimethylphenanthren- 2-yl]propenoic acid

Crystal data

C20H30O3	Dx = 1.176 Mg m^−3
Mr = 318.44	Melting point: 490.5-492.5K K
Monoclinic, C2	Mo Kα radiation, λ = 0.71073 Å
a = 24.066 (2) Å	Cell parameters from 25 reflections
b = 10.017 (1) Å	θ = 3.3–12.3°
c = 7.608 (1) Å	µ = 0.08 mm^−1
β = 101.35 (1)°	T = 295 K
V = 1798.2 (3) Å^3	Prism, colorless
Z = 4	0.50 × 0.50 × 0.40 mm
F(000) = 696

Data collection

Siemens P4 diffractometer	Rint = 0.016
Radiation source: normal-focus sealed tube	θmax = 27.5°, θmin = 1.7°
Graphite monochromator	h = 0→31
ω scans	k = 0→13
2311 measured reflections	l = −9→9
2178 independent reflections	3 standard reflections every 97 reflections
1605 reflections with I > 2σ(I)	intensity decay: 1.3%

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.040	w = 1/[σ^2(Fo^2) + (0.0509P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.097	(Δ/σ)max < 0.001
S = 0.98	Δρmax = 0.15 e Å^−3
2178 reflections	Δρmin = −0.12 e Å^−3
214 parameters	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
1 restraint	Extinction coefficient: 0.035 (2)
Primary atom site location: structure-invariant direct methods	Absolute structure: see text
Secondary atom site location: difference Fourier map

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	0.90473 (7)	0.3283 (2)	0.8642 (2)	0.0532 (5)
H1O	0.9180	0.3124	0.9699	0.064*
O2	0.53159 (7)	0.75895 (18)	0.8040 (3)	0.0541 (5)
O3	0.45819 (7)	0.62074 (19)	0.7549 (3)	0.0648 (6)
H3O	0.4414	0.6885	0.7756	0.078*
C1	0.83633 (10)	0.5363 (3)	0.9824 (3)	0.0532 (7)
H1A	0.8278	0.5933	1.0767	0.064*
H1B	0.8295	0.4447	1.0134	0.064*
C2	0.89867 (11)	0.5522 (3)	0.9736 (4)	0.0579 (8)
H2A	0.9063	0.6450	0.9508	0.070*
H2B	0.9219	0.5275	1.0882	0.070*
C3	0.91440 (10)	0.4655 (3)	0.8268 (3)	0.0488 (7)
H3	0.9547	0.4779	0.8259	0.059*
C4	0.87985 (10)	0.4993 (3)	0.6406 (3)	0.0470 (6)
C5	0.81543 (9)	0.4995 (2)	0.6465 (3)	0.0396 (5)
H5	0.8062	0.4054	0.6611	0.048*
C6	0.77756 (10)	0.5410 (3)	0.4699 (3)	0.0531 (7)
H6A	0.7857	0.6329	0.4434	0.064*
H6B	0.7858	0.4854	0.3738	0.064*
C7	0.71645 (11)	0.5280 (3)	0.4782 (3)	0.0534 (7)
H7	0.6900	0.5310	0.3712	0.064*
C8	0.69758 (10)	0.5125 (3)	0.6285 (3)	0.0426 (6)
C9	0.73609 (9)	0.5174 (3)	0.8114 (3)	0.0400 (5)
H9	0.7413	0.4247	0.8524	0.048*
C10	0.79625 (10)	0.5718 (3)	0.8048 (3)	0.0407 (6)
C11	0.70718 (9)	0.5897 (4)	0.9470 (3)	0.0616 (8)
H11A	0.7297	0.5768	1.0664	0.074*
H11B	0.7063	0.6847	0.9215	0.074*
C12	0.64725 (10)	0.5421 (3)	0.9445 (3)	0.0592 (8)
H12A	0.6311	0.5924	1.0313	0.071*
H12B	0.6479	0.4486	0.9781	0.071*
C13	0.61058 (9)	0.5600 (3)	0.7583 (3)	0.0432 (6)
H13	0.6131	0.6541	0.7256	0.052*
C14	0.63637 (10)	0.4785 (3)	0.6268 (3)	0.0544 (7)
H14A	0.6337	0.3846	0.6549	0.065*
H14B	0.6145	0.4929	0.5069	0.065*
C15	0.54878 (10)	0.5299 (3)	0.7544 (3)	0.0486 (6)
C16	0.51282 (10)	0.6467 (3)	0.7736 (3)	0.0429 (6)
C17	0.52643 (13)	0.4102 (3)	0.7418 (5)	0.0889 (13)
H17A	0.4883	0.3992	0.7450	0.107*
H17B	0.5487	0.3362	0.7297	0.107*
C18	0.90256 (13)	0.6308 (3)	0.5786 (5)	0.0764 (10)
H18A	0.9416	0.6198	0.5705	0.092*
H18B	0.8994	0.7000	0.6633	0.092*
H18C	0.8809	0.6547	0.4631	0.092*
C19	0.89093 (12)	0.3919 (3)	0.5080 (4)	0.0627 (8)
H19A	0.8738	0.3094	0.5336	0.075*
H19B	0.9310	0.3795	0.5194	0.075*
H19C	0.8749	0.4196	0.3880	0.075*
C20	0.79329 (13)	0.7233 (3)	0.7790 (4)	0.0625 (8)
H20A	0.8286	0.7551	0.7545	0.075*
H20B	0.7862	0.7650	0.8860	0.075*
H20C	0.7632	0.7450	0.6802	0.075*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0468 (10)	0.0565 (11)	0.0572 (11)	0.0140 (8)	0.0123 (9)	0.0107 (9)
O2	0.0397 (10)	0.0500 (11)	0.0724 (12)	0.0019 (8)	0.0103 (8)	−0.0115 (10)
O3	0.0347 (9)	0.0578 (13)	0.1020 (16)	0.0043 (9)	0.0137 (10)	−0.0135 (11)
C1	0.0421 (14)	0.073 (2)	0.0420 (14)	0.0109 (13)	0.0028 (11)	−0.0117 (14)
C2	0.0450 (14)	0.070 (2)	0.0551 (16)	0.0043 (13)	0.0001 (12)	−0.0117 (15)
C3	0.0335 (12)	0.0515 (16)	0.0622 (17)	0.0016 (11)	0.0111 (11)	−0.0009 (13)
C4	0.0421 (13)	0.0496 (15)	0.0531 (15)	0.0028 (11)	0.0184 (11)	0.0066 (12)
C5	0.0396 (12)	0.0390 (14)	0.0410 (12)	0.0057 (10)	0.0098 (10)	0.0000 (11)
C6	0.0556 (15)	0.0665 (19)	0.0389 (13)	0.0123 (14)	0.0132 (11)	0.0056 (13)
C7	0.0461 (14)	0.0743 (19)	0.0363 (13)	0.0144 (14)	−0.0001 (11)	−0.0022 (14)
C8	0.0388 (12)	0.0466 (14)	0.0409 (12)	0.0114 (11)	0.0043 (10)	−0.0059 (11)
C9	0.0373 (12)	0.0460 (13)	0.0366 (12)	0.0133 (11)	0.0073 (9)	0.0012 (11)
C10	0.0381 (12)	0.0413 (13)	0.0417 (13)	0.0060 (10)	0.0051 (10)	−0.0022 (11)
C11	0.0397 (13)	0.103 (2)	0.0408 (14)	0.0161 (15)	0.0036 (11)	−0.0162 (16)
C12	0.0452 (14)	0.088 (2)	0.0461 (15)	0.0207 (15)	0.0122 (11)	0.0002 (15)
C13	0.0362 (12)	0.0439 (14)	0.0491 (14)	0.0104 (11)	0.0077 (10)	0.0032 (12)
C14	0.0437 (14)	0.0656 (19)	0.0527 (15)	0.0064 (13)	0.0063 (11)	−0.0126 (13)
C15	0.0413 (13)	0.0454 (15)	0.0595 (15)	0.0048 (12)	0.0111 (11)	0.0001 (13)
C16	0.0337 (12)	0.0513 (16)	0.0423 (14)	0.0052 (11)	0.0043 (10)	−0.0005 (12)
C17	0.060 (2)	0.0477 (19)	0.166 (4)	0.0026 (16)	0.038 (2)	−0.001 (2)
C18	0.0600 (18)	0.073 (2)	0.103 (3)	0.0001 (17)	0.0308 (17)	0.024 (2)
C19	0.0587 (17)	0.076 (2)	0.0580 (17)	0.0187 (16)	0.0238 (13)	0.0033 (16)
C20	0.0612 (18)	0.0430 (16)	0.084 (2)	0.0073 (13)	0.0164 (15)	−0.0148 (15)

Geometric parameters (Å, º)

O1—C3	1.432 (3)	C9—C10	1.557 (3)
O1—H1O	0.8200	C9—H9	0.9800
O2—C16	1.217 (3)	C10—C20	1.530 (4)
O3—C16	1.320 (3)	C11—C12	1.516 (4)
O3—H3O	0.8200	C11—H11A	0.9700
C1—C2	1.523 (3)	C11—H11B	0.9700
C1—C10	1.539 (3)	C12—C13	1.525 (3)
C1—H1A	0.9700	C12—H12A	0.9700
C1—H1B	0.9700	C12—H12B	0.9700
C2—C3	1.520 (4)	C13—C15	1.512 (3)
C2—H2A	0.9700	C13—C14	1.516 (3)
C2—H2B	0.9700	C13—H13	0.9800
C3—C4	1.533 (4)	C14—H14A	0.9700
C3—H3	0.9800	C14—H14B	0.9700
C4—C19	1.534 (4)	C15—C17	1.310 (4)
C4—C18	1.535 (4)	C15—C16	1.479 (3)
C4—C5	1.560 (3)	C17—H17A	0.9300
C5—C6	1.526 (3)	C17—H17B	0.9300
C5—C10	1.552 (3)	C18—H18A	0.9600
C5—H5	0.9800	C18—H18B	0.9600
C6—C7	1.490 (3)	C18—H18C	0.9600
C6—H6A	0.9700	C19—H19A	0.9600
C6—H6B	0.9700	C19—H19B	0.9600
C7—C8	1.320 (3)	C19—H19C	0.9600
C7—H7	0.9300	C20—H20A	0.9600
C8—C14	1.510 (3)	C20—H20B	0.9600
C8—C9	1.513 (3)	C20—H20C	0.9600
C9—C11	1.535 (3)
C3—O1—H1O	109.5	C1—C10—C9	108.47 (19)
C16—O3—H3O	109.5	C5—C10—C9	106.37 (18)
C2—C1—C10	113.0 (2)	C12—C11—C9	113.5 (2)
C2—C1—H1A	109.0	C12—C11—H11A	108.9
C10—C1—H1A	109.0	C9—C11—H11A	108.9
C2—C1—H1B	109.0	C12—C11—H11B	108.9
C10—C1—H1B	109.0	C9—C11—H11B	108.9
H1A—C1—H1B	107.8	H11A—C11—H11B	107.7
C3—C2—C1	111.2 (2)	C11—C12—C13	110.5 (2)
C3—C2—H2A	109.4	C11—C12—H12A	109.6
C1—C2—H2A	109.4	C13—C12—H12A	109.6
C3—C2—H2B	109.4	C11—C12—H12B	109.6
C1—C2—H2B	109.4	C13—C12—H12B	109.6
H2A—C2—H2B	108.0	H12A—C12—H12B	108.1
O1—C3—C2	109.2 (2)	C15—C13—C14	114.1 (2)
O1—C3—C4	108.4 (2)	C15—C13—C12	112.5 (2)
C2—C3—C4	112.6 (2)	C14—C13—C12	108.22 (19)
O1—C3—H3	108.9	C15—C13—H13	107.2
C2—C3—H3	108.9	C14—C13—H13	107.2
C4—C3—H3	108.9	C12—C13—H13	107.2
C3—C4—C19	108.7 (2)	C8—C14—C13	113.5 (2)
C3—C4—C18	108.2 (2)	C8—C14—H14A	108.9
C19—C4—C18	106.3 (2)	C13—C14—H14A	108.9
C3—C4—C5	109.60 (18)	C8—C14—H14B	108.9
C19—C4—C5	108.8 (2)	C13—C14—H14B	108.9
C18—C4—C5	115.1 (2)	H14A—C14—H14B	107.7
C6—C5—C10	109.80 (19)	C17—C15—C16	119.4 (2)
C6—C5—C4	113.58 (19)	C17—C15—C13	124.9 (2)
C10—C5—C4	118.2 (2)	C16—C15—C13	115.6 (2)
C6—C5—H5	104.6	O2—C16—O3	121.8 (2)
C10—C5—H5	104.6	O2—C16—C15	123.2 (2)
C4—C5—H5	104.6	O3—C16—C15	115.0 (2)
C7—C6—C5	111.2 (2)	C15—C17—H17A	120.0
C7—C6—H6A	109.4	C15—C17—H17B	120.0
C5—C6—H6A	109.4	H17A—C17—H17B	120.0
C7—C6—H6B	109.4	C4—C18—H18A	109.5
C5—C6—H6B	109.4	C4—C18—H18B	109.5
H6A—C6—H6B	108.0	H18A—C18—H18B	109.5
C8—C7—C6	123.9 (2)	C4—C18—H18C	109.5
C8—C7—H7	118.0	H18A—C18—H18C	109.5
C6—C7—H7	118.0	H18B—C18—H18C	109.5
C7—C8—C14	121.4 (2)	C4—C19—H19A	109.5
C7—C8—C9	122.7 (2)	C4—C19—H19B	109.5
C14—C8—C9	115.8 (2)	H19A—C19—H19B	109.5
C8—C9—C11	110.90 (18)	C4—C19—H19C	109.5
C8—C9—C10	112.76 (19)	H19A—C19—H19C	109.5
C11—C9—C10	113.8 (2)	H19B—C19—H19C	109.5
C8—C9—H9	106.3	C10—C20—H20A	109.5
C11—C9—H9	106.3	C10—C20—H20B	109.5
C10—C9—H9	106.3	H20A—C20—H20B	109.5
C20—C10—C1	110.3 (2)	C10—C20—H20C	109.5
C20—C10—C5	112.2 (2)	H20A—C20—H20C	109.5
C1—C10—C5	110.02 (19)	H20B—C20—H20C	109.5
C20—C10—C9	109.4 (2)
C10—C1—C2—C3	−58.3 (3)	C4—C5—C10—C20	78.8 (3)
C1—C2—C3—O1	−60.9 (3)	C6—C5—C10—C1	−176.9 (2)
C1—C2—C3—C4	59.6 (3)	C4—C5—C10—C1	−44.4 (3)
O1—C3—C4—C19	−49.2 (3)	C6—C5—C10—C9	65.8 (2)
C2—C3—C4—C19	−170.1 (2)	C4—C5—C10—C9	−161.74 (19)
O1—C3—C4—C18	−164.2 (2)	C8—C9—C10—C20	75.4 (3)
C2—C3—C4—C18	74.9 (3)	C11—C9—C10—C20	−52.0 (3)
O1—C3—C4—C5	69.6 (2)	C8—C9—C10—C1	−164.2 (2)
C2—C3—C4—C5	−51.4 (3)	C11—C9—C10—C1	68.4 (3)
C3—C4—C5—C6	176.3 (2)	C8—C9—C10—C5	−45.9 (3)
C19—C4—C5—C6	−65.1 (3)	C11—C9—C10—C5	−173.3 (2)
C18—C4—C5—C6	54.0 (3)	C8—C9—C11—C12	48.0 (3)
C3—C4—C5—C10	45.5 (3)	C10—C9—C11—C12	176.4 (2)
C19—C4—C5—C10	164.2 (2)	C9—C11—C12—C13	−58.2 (3)
C18—C4—C5—C10	−76.7 (3)	C11—C12—C13—C15	−172.9 (2)
C10—C5—C6—C7	−50.2 (3)	C11—C12—C13—C14	60.1 (3)
C4—C5—C6—C7	175.1 (2)	C7—C8—C14—C13	−135.3 (3)
C5—C6—C7—C8	14.4 (4)	C9—C8—C14—C13	49.0 (3)
C6—C7—C8—C14	−170.3 (3)	C15—C13—C14—C8	178.3 (2)
C6—C7—C8—C9	5.1 (4)	C12—C13—C14—C8	−55.7 (3)
C7—C8—C9—C11	141.2 (3)	C14—C13—C15—C17	41.7 (4)
C14—C8—C9—C11	−43.2 (3)	C12—C13—C15—C17	−82.1 (4)
C7—C8—C9—C10	12.3 (3)	C14—C13—C15—C16	−140.8 (2)
C14—C8—C9—C10	−172.1 (2)	C12—C13—C15—C16	95.4 (3)
C2—C1—C10—C20	−75.0 (3)	C17—C15—C16—O2	172.4 (3)
C2—C1—C10—C5	49.2 (3)	C13—C15—C16—O2	−5.3 (4)
C2—C1—C10—C9	165.2 (2)	C17—C15—C16—O3	−7.8 (4)
C6—C5—C10—C20	−53.7 (3)	C13—C15—C16—O3	174.6 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3O···O1^i	0.82	1.85	2.662 (3)	169
O1—H1O···O2^ii	0.82	1.97	2.771 (3)	164

Symmetry codes: (i) x−1/2, y+1/2, z; (ii) −x+3/2, y−1/2, −z+2.