Tetra-hydro-alstonine.

In the title compound, C21H24N2O3 [systematic name: methyl (20α)-16,17-dide-hydro-19α-methyl-18-oxayohimban-16-carb-oxy-l-ate], the mol-ecule adopts an L-type conformation. The crystal packing is governed by one N-H⋯π and one C-H⋯π inter-actions. The crystal cohesion is ensured by inter-molecular van der Waals contacts [shortest O⋯O contact = 3.199 (2) Å].

Related literature

For the extraction of tetra­hydro­alstonine (THA) from natural sources, see: Zenk & Juenger (2007 ▶); Mandal et al. (1983 ▶); Langlois et al. (1979 ▶). For stereochemistry studies, see: Wenkert et al. (1961 ▶); Wenkert & Roychaudhuri (1957 ▶); Shamma & Richey (1963 ▶); Lounasmaa & Kan (1980 ▶); Höfle et al. (1980 ▶). For the semisynthesis, see: Poirot (2007 ▶); Beziat & Hatinguais (1977 ▶); Zsadon et al. (1979 ▶); Guéritte et al. (1983 ▶); Hemscheidt & Zenk (1985 ▶) and for synthetic studies, see: Gutzwiller et al. (1971 ▶); Wenkert et al. (1976 ▶); Zou et al. (2010 ▶). For the biological activity of TMA, see Zou et al. (2010 ▶); Sharma et al. (1988 ▶). For a related structure, see: Laus & Wurst (2008 ▶).

Experimental

Crystal data

C21H24N2O3

M = 352.42

Orthorhombic,

a = 6.719 (1) Å

b = 8.169 (2) Å

c = 34.120 (5) Å

V = 1872.8 (6) Å3

Z = 4

Mo Kα radiation

μ = 0.08 mm−1

T = 293 K

0.50 × 0.30 × 0.10 mm

Data collection

Nonius KappaCCD diffractometer

Absorption correction: multi-scan (COLLECT; Nonius, 2004 ▶) T min = 0.982, T max = 0.992

3300 measured reflections

3300 independent reflections

2537 reflections with I > 2σ(I)

Refinement

R[F 2 > 2σ(F 2)] = 0.044

wR(F 2) = 0.114

S = 1.01

3300 reflections

247 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.11 e Å−3

Δρmin = −0.12 e Å−3

Absolute structure parameter: −0.3 (17)

Data collection: COLLECT (Nonius, 2004 ▶); cell refinement: SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO (Otwinowski & Minor, 1997 ▶) and SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶); software used to prepare material for publication: WinGX (Farrugia, 2012 ▶).

Crystal structure: contains datablock(s) I. DOI: 10.1107/S1600536813021168/bq2388sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813021168/bq2388Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C21H24N2O3	F(000) = 752
Mr = 352.42	Dx = 1.250 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71069 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1924 reflections
a = 6.719 (1) Å	θ = 0.4–25.4°
b = 8.169 (2) Å	µ = 0.08 mm−1
c = 34.120 (5) Å	T = 293 K
V = 1872.8 (6) Å3	Parallelepiped, colourless
Z = 4	0.50 × 0.30 × 0.10 mm

Nonius KappaCCD diffractometer	3300 independent reflections
Radiation source: fine-focus sealed tube	2537 reflections with I > 2σ(I)
Horizonally mounted graphite crystal monochromator	Rint = 0.000
Detector resolution: 9 pixels mm-1	θmax = 25.3°, θmin = 3.5°
CCD scans	h = −8→8
Absorption correction: multi-scan (COLLECT; Nonius, 2004)	k = −9→9
Tmin = 0.982, Tmax = 0.992	l = −40→40
3300 measured reflections

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.114	H atoms treated by a mixture of independent and constrained refinement
S = 1.01	w = 1/[σ2(Fo2) + (0.0585P)2 + 0.175P] where P = (Fo2 + 2Fc2)/3
3300 reflections	(Δ/σ)max < 0.001
247 parameters	Δρmax = 0.11 e Å−3
0 restraints	Δρmin = −0.12 e Å−3

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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.

	x	y	z	Uiso*/Ueq
N1	0.0941 (2)	1.03273 (19)	0.22093 (5)	0.0543 (4)
H1	0.0106	1.0929	0.2084	0.065*
C2	0.2643 (3)	0.9635 (2)	0.20539 (6)	0.0498 (4)
C3	0.3268 (3)	0.9745 (3)	0.16349 (6)	0.0554 (5)
H3	0.388 (3)	1.082 (3)	0.1594 (6)	0.072 (6)*
N4	0.4687 (2)	0.8412 (2)	0.15597 (6)	0.0661 (5)
C5	0.6291 (3)	0.8379 (3)	0.18547 (8)	0.0769 (7)
H5A	0.6887	0.9457	0.1874	0.092*
H5B	0.7315	0.7616	0.1772	0.092*
C6	0.5502 (3)	0.7872 (3)	0.22502 (8)	0.0703 (6)
H6A	0.5248	0.6704	0.2252	0.084*
H6B	0.6483	0.8111	0.2451	0.084*
C7	0.3616 (3)	0.8781 (2)	0.23357 (6)	0.0560 (5)
C8	0.2480 (3)	0.8919 (2)	0.26876 (6)	0.0561 (5)
C9	0.2699 (4)	0.8333 (3)	0.30708 (7)	0.0713 (6)
H9	0.3806	0.7713	0.3139	0.086*
C10	0.1262 (5)	0.8682 (3)	0.33441 (8)	0.0834 (8)
H10	0.1396	0.8284	0.3598	0.100*
C11	−0.0392 (5)	0.9624 (3)	0.32467 (7)	0.0834 (7)
H11	−0.1357	0.9828	0.3436	0.100*
C12	−0.0628 (4)	1.0259 (3)	0.28766 (6)	0.0701 (6)
H12	−0.1717	1.0912	0.2815	0.084*
C13	0.0803 (3)	0.9893 (2)	0.25995 (6)	0.0542 (5)
C14	0.1540 (3)	0.9621 (3)	0.13484 (5)	0.0536 (5)
H14A	0.0620	1.0515	0.1395	0.064*
H14B	0.0834	0.8602	0.1392	0.064*
C15	0.2267 (4)	0.9687 (3)	0.09227 (6)	0.0640 (6)
H15	0.281 (4)	1.076 (3)	0.0888 (7)	0.073 (7)*
C16	0.0636 (4)	0.9412 (3)	0.06288 (6)	0.0662 (6)
C17	0.0518 (5)	0.8003 (3)	0.04332 (7)	0.0847 (8)
H17	−0.0469	0.7924	0.0243	0.102*
O18	0.1678 (3)	0.6694 (2)	0.04839 (6)	0.1032 (7)
C19	0.3020 (5)	0.6744 (3)	0.08207 (8)	0.0872 (8)
H19	0.2254	0.6518	0.1059	0.105*
C20	0.3918 (4)	0.8443 (3)	0.08520 (8)	0.0797 (7)
H20	0.465 (4)	0.871 (3)	0.0595 (7)	0.088 (7)*
C21	0.5520 (4)	0.8600 (4)	0.11650 (8)	0.0887 (8)
H21A	0.6530	0.7770	0.1122	0.106*
H21B	0.6151	0.9664	0.1143	0.106*
C22	0.4475 (7)	0.5356 (4)	0.07534 (11)	0.1426 (15)
H22A	0.5421	0.5670	0.0556	0.214*
H22B	0.3765	0.4401	0.0668	0.214*
H22C	0.5162	0.5117	0.0993	0.214*
C23	−0.0746 (4)	1.0739 (3)	0.05479 (6)	0.0695 (6)
O24	−0.2128 (3)	1.0354 (2)	0.02800 (5)	0.0910 (6)
O25	−0.0672 (3)	1.2070 (2)	0.06996 (5)	0.0945 (6)
C26	−0.3520 (5)	1.1602 (4)	0.01729 (10)	0.1060 (10)
H26A	−0.2815	1.2528	0.0069	0.159*
H26B	−0.4264	1.1930	0.0400	0.159*
H26C	−0.4414	1.1184	−0.0023	0.159*

	U11	U22	U33	U12	U13	U23
N1	0.0552 (9)	0.0540 (8)	0.0537 (9)	0.0087 (8)	−0.0107 (8)	−0.0008 (8)
C2	0.0463 (10)	0.0450 (9)	0.0581 (11)	0.0012 (9)	−0.0105 (9)	−0.0051 (8)
C3	0.0481 (11)	0.0531 (11)	0.0651 (13)	−0.0025 (10)	−0.0025 (9)	−0.0021 (10)
N4	0.0456 (9)	0.0757 (12)	0.0770 (13)	0.0066 (9)	0.0038 (9)	−0.0051 (9)
C5	0.0452 (12)	0.0821 (16)	0.103 (2)	0.0048 (12)	−0.0055 (13)	−0.0034 (15)
C6	0.0513 (12)	0.0617 (12)	0.0980 (18)	0.0078 (11)	−0.0201 (13)	−0.0022 (12)
C7	0.0530 (11)	0.0462 (10)	0.0687 (14)	0.0017 (9)	−0.0153 (10)	−0.0056 (9)
C8	0.0641 (12)	0.0417 (9)	0.0625 (13)	−0.0021 (10)	−0.0205 (11)	−0.0017 (9)
C9	0.0917 (17)	0.0530 (12)	0.0691 (15)	−0.0038 (13)	−0.0249 (14)	0.0064 (11)
C10	0.125 (2)	0.0657 (14)	0.0599 (15)	−0.0183 (17)	−0.0172 (16)	0.0068 (11)
C11	0.115 (2)	0.0756 (14)	0.0595 (14)	−0.0120 (18)	0.0064 (14)	−0.0098 (12)
C12	0.0783 (15)	0.0660 (12)	0.0661 (14)	0.0020 (13)	−0.0016 (12)	−0.0122 (11)
C13	0.0597 (11)	0.0488 (10)	0.0540 (11)	0.0013 (9)	−0.0095 (9)	−0.0051 (8)
C14	0.0508 (11)	0.0587 (11)	0.0512 (11)	0.0008 (10)	0.0007 (9)	−0.0045 (9)
C15	0.0718 (15)	0.0622 (12)	0.0579 (12)	−0.0037 (13)	0.0122 (11)	0.0005 (10)
C16	0.0851 (16)	0.0686 (14)	0.0451 (11)	−0.0008 (13)	0.0087 (11)	0.0000 (10)
C17	0.116 (2)	0.0844 (17)	0.0538 (14)	0.0096 (18)	−0.0026 (14)	−0.0102 (12)
O18	0.1444 (18)	0.0837 (12)	0.0815 (13)	0.0226 (13)	−0.0117 (13)	−0.0251 (10)
C19	0.116 (2)	0.0745 (16)	0.0709 (16)	0.0229 (16)	0.0094 (16)	−0.0093 (12)
C20	0.0769 (16)	0.0944 (18)	0.0676 (15)	0.0116 (15)	0.0276 (14)	−0.0005 (13)
C21	0.0621 (15)	0.111 (2)	0.0934 (19)	0.0084 (16)	0.0258 (15)	−0.0032 (16)
C22	0.191 (4)	0.117 (2)	0.120 (3)	0.072 (3)	−0.003 (3)	−0.029 (2)
C23	0.0886 (17)	0.0782 (16)	0.0418 (11)	0.0033 (14)	0.0077 (12)	0.0046 (10)
O24	0.1015 (13)	0.1035 (13)	0.0679 (10)	0.0172 (12)	−0.0157 (9)	−0.0089 (9)
O25	0.1331 (17)	0.0745 (10)	0.0759 (12)	0.0125 (12)	−0.0110 (11)	−0.0040 (9)
C26	0.102 (2)	0.122 (2)	0.094 (2)	0.027 (2)	−0.0055 (17)	0.0224 (17)

N1—C2	1.382 (3)	C14—H14A	0.9700
N1—C13	1.381 (2)	C14—H14B	0.9700
N1—H1	0.8600	C15—C16	1.502 (3)
C2—C7	1.356 (3)	C15—C20	1.524 (3)
C2—C3	1.492 (3)	C15—H15	0.96 (2)
C3—N4	1.470 (3)	C16—C17	1.333 (3)
C3—C14	1.521 (3)	C16—C23	1.454 (3)
C3—H3	0.98 (2)	C17—O18	1.334 (3)
N4—C21	1.466 (3)	C17—H17	0.9300
N4—C5	1.475 (3)	O18—C19	1.461 (3)
C5—C6	1.508 (3)	O18—O24i	3.199 (2)
C5—H5A	0.9700	C19—C22	1.515 (4)
C5—H5B	0.9700	C19—C20	1.517 (4)
C6—C7	1.497 (3)	C19—H19	0.9800
C6—H6A	0.9700	C20—C21	1.522 (4)
C6—H6B	0.9700	C20—H20	1.03 (3)
C7—C8	1.427 (3)	C21—H21A	0.9700
C8—C9	1.400 (3)	C21—H21B	0.9700
C8—C13	1.412 (3)	C22—H22A	0.9600
C9—C10	1.372 (4)	C22—H22B	0.9600
C9—H9	0.9300	C22—H22C	0.9600
C10—C11	1.392 (4)	C23—O25	1.205 (3)
C10—H10	0.9300	C23—O24	1.340 (3)
C11—C12	1.374 (3)	O24—C26	1.430 (3)
C11—H11	0.9300	C26—H26A	0.9600
C12—C13	1.381 (3)	C26—H26B	0.9600
C12—H12	0.9300	C26—H26C	0.9600
C14—C15	1.533 (3)
C2—N1—C13	108.68 (16)	C15—C14—H14B	109.4
C2—N1—H1	125.7	H14A—C14—H14B	108.0
C13—N1—H1	125.7	C16—C15—C20	109.01 (19)
C7—C2—N1	109.74 (19)	C16—C15—C14	113.25 (19)
C7—C2—C3	125.07 (18)	C20—C15—C14	111.00 (19)
N1—C2—C3	125.14 (17)	C16—C15—H15	109.3 (14)
N4—C3—C2	107.76 (17)	C20—C15—H15	108.5 (14)
N4—C3—C14	109.48 (16)	C14—C15—H15	105.7 (14)
C2—C3—C14	113.41 (16)	C17—C16—C23	120.7 (2)
N4—C3—H3	111.4 (13)	C17—C16—C15	120.5 (2)
C2—C3—H3	107.9 (13)	C23—C16—C15	118.75 (19)
C14—C3—H3	106.9 (13)	C16—C17—O18	126.3 (3)
C21—N4—C3	109.28 (18)	C16—C17—H17	116.8
C21—N4—C5	110.49 (19)	O18—C17—H17	116.8
C3—N4—C5	111.60 (17)	C17—O18—C19	116.12 (18)
N4—C5—C6	111.05 (18)	C17—O18—O24i	117.37 (15)
N4—C5—H5A	109.4	C19—O18—O24i	120.05 (15)
C6—C5—H5A	109.4	O18—C19—C22	105.0 (2)
N4—C5—H5B	109.4	O18—C19—C20	109.0 (2)
C6—C5—H5B	109.4	C22—C19—C20	116.0 (3)
H5A—C5—H5B	108.0	O18—C19—H19	108.9
C7—C6—C5	109.63 (18)	C22—C19—H19	108.9
C7—C6—H6A	109.7	C20—C19—H19	108.9
C5—C6—H6A	109.7	C19—C20—C21	114.0 (2)
C7—C6—H6B	109.7	C19—C20—C15	109.4 (2)
C5—C6—H6B	109.7	C21—C20—C15	110.4 (2)
H6A—C6—H6B	108.2	C19—C20—H20	108.9 (14)
C2—C7—C8	107.32 (17)	C21—C20—H20	104.1 (14)
C2—C7—C6	121.7 (2)	C15—C20—H20	109.9 (14)
C8—C7—C6	130.99 (19)	N4—C21—C20	111.5 (2)
C9—C8—C13	118.4 (2)	N4—C21—H21A	109.3
C9—C8—C7	134.6 (2)	C20—C21—H21A	109.3
C13—C8—C7	107.01 (17)	N4—C21—H21B	109.3
C10—C9—C8	119.3 (2)	C20—C21—H21B	109.3
C10—C9—H9	120.3	H21A—C21—H21B	108.0
C8—C9—H9	120.3	C19—C22—H22A	109.5
C9—C10—C11	120.9 (2)	C19—C22—H22B	109.5
C9—C10—H10	119.5	H22A—C22—H22B	109.5
C11—C10—H10	119.5	C19—C22—H22C	109.5
C12—C11—C10	121.3 (2)	H22A—C22—H22C	109.5
C12—C11—H11	119.3	H22B—C22—H22C	109.5
C10—C11—H11	119.3	O25—C23—O24	122.2 (2)
C11—C12—C13	117.8 (2)	O25—C23—C16	124.4 (2)
C11—C12—H12	121.1	O24—C23—C16	113.4 (2)
C13—C12—H12	121.1	C23—O24—C26	117.4 (2)
C12—C13—N1	130.62 (19)	O24—C26—H26A	109.5
C12—C13—C8	122.13 (19)	O24—C26—H26B	109.5
N1—C13—C8	107.25 (18)	H26A—C26—H26B	109.5
C3—C14—C15	111.33 (17)	O24—C26—H26C	109.5
C3—C14—H14A	109.4	H26A—C26—H26C	109.5
C15—C14—H14A	109.4	H26B—C26—H26C	109.5
C3—C14—H14B	109.4
C13—N1—C2—C7	−0.7 (2)	C7—C8—C13—N1	−0.3 (2)
C13—N1—C2—C3	176.71 (18)	N4—C3—C14—C15	−57.9 (2)
C7—C2—C3—N4	17.0 (3)	C2—C3—C14—C15	−178.22 (18)
N1—C2—C3—N4	−159.97 (17)	C3—C14—C15—C16	174.62 (19)
C7—C2—C3—C14	138.4 (2)	C3—C14—C15—C20	51.6 (3)
N1—C2—C3—C14	−38.6 (3)	C20—C15—C16—C17	17.6 (3)
C2—C3—N4—C21	−173.13 (18)	C14—C15—C16—C17	−106.5 (3)
C14—C3—N4—C21	63.1 (2)	C20—C15—C16—C23	−159.33 (19)
C2—C3—N4—C5	−50.6 (2)	C14—C15—C16—C23	76.6 (3)
C14—C3—N4—C5	−174.38 (18)	C23—C16—C17—O18	−179.2 (2)
C21—N4—C5—C6	−169.4 (2)	C15—C16—C17—O18	4.0 (4)
C3—N4—C5—C6	68.8 (2)	C16—C17—O18—C19	8.7 (4)
N4—C5—C6—C7	−45.6 (2)	C16—C17—O18—O24i	−143.1 (2)
N1—C2—C7—C8	0.5 (2)	C17—O18—C19—C22	−166.5 (3)
C3—C2—C7—C8	−176.90 (18)	O24i—O18—C19—C22	−15.5 (3)
N1—C2—C7—C6	178.97 (16)	C17—O18—C19—C20	−41.6 (3)
C3—C2—C7—C6	1.6 (3)	O24i—O18—C19—C20	109.46 (19)
C5—C6—C7—C2	12.5 (3)	O18—C19—C20—C21	−173.59 (19)
C5—C6—C7—C8	−169.4 (2)	C22—C19—C20—C21	−55.4 (3)
C2—C7—C8—C9	−179.6 (2)	O18—C19—C20—C15	62.3 (3)
C6—C7—C8—C9	2.1 (4)	C22—C19—C20—C15	−179.5 (2)
C2—C7—C8—C13	−0.1 (2)	C16—C15—C20—C19	−49.3 (3)
C6—C7—C8—C13	−178.41 (19)	C14—C15—C20—C19	76.1 (3)
C13—C8—C9—C10	1.8 (3)	C16—C15—C20—C21	−175.5 (2)
C7—C8—C9—C10	−178.8 (2)	C14—C15—C20—C21	−50.1 (3)
C8—C9—C10—C11	−0.7 (3)	C3—N4—C21—C20	−63.3 (3)
C9—C10—C11—C12	−1.1 (4)	C5—N4—C21—C20	173.5 (2)
C10—C11—C12—C13	1.8 (3)	C19—C20—C21—N4	−67.0 (3)
C11—C12—C13—N1	178.8 (2)	C15—C20—C21—N4	56.6 (3)
C11—C12—C13—C8	−0.7 (3)	C17—C16—C23—O25	−176.4 (3)
C2—N1—C13—C12	−179.0 (2)	C15—C16—C23—O25	0.5 (3)
C2—N1—C13—C8	0.6 (2)	C17—C16—C23—O24	2.8 (3)
C9—C8—C13—C12	−1.0 (3)	C15—C16—C23—O24	179.7 (2)
C7—C8—C13—C12	179.33 (19)	O25—C23—O24—C26	1.0 (4)
C9—C8—C13—N1	179.34 (18)	C16—C23—O24—C26	−178.2 (2)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···Cg1ii	0.86	2.85	3.550 (2)	139
C6—H6A···Cg2iii	0.97	2.8	3.429 (3)	121

Table 1

Hydrogen-bond geometry (Å, °)

Cg1 and Cg2 are the centroids of the C8–C13 and C2/C7/C8/C13/N1 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯Cg1i	0.86	2.85	3.550 (2)	139
C6—H6A⋯Cg2ii	0.97	2.8	3.429 (3)	121

Symmetry codes: (i) ; (ii) .