Tetra­hydro­alstonine

Xavier Cachet; François-Hugues Porée; Sylvie Michel; Pascale Lemoine

doi:10.1107/S1600536813021168

. 2013 Aug 7;69(Pt 9):o1389–o1390. doi: 10.1107/S1600536813021168

Tetrahydroalstonine

Xavier Cachet ^a, François-Hugues Porée ^a,^*, Sylvie Michel ^a, Pascale Lemoine ^b

PMCID: PMC3884471 PMID: 24427031

Abstract

In the title compound, C₂₁H₂₄N₂O₃ [systematic name: methyl (20α)-16,17-didehydro-19α-methyl-18-oxayohimban-16-carboxylate], the molecule adopts an L-type conformation. The crystal packing is governed by one N—H⋯π and one C—H⋯π interactions. The crystal cohesion is ensured by intermolecular 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 _r = 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
Δρ_max = 0.11 e Å⁻³
Δρ_min = −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 ▶).

Supplementary Material

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

e-69-o1389-sup1.cif^{(30.6KB, cif)}

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

e-69-o1389-Isup2.hkl^{(158.6KB, hkl)}

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

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

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors thank Université Paris Descartes and the CNRS for financial support.

supplementary crystallographic information

1. Comment

Tetrahydroalstonine (THA) is an indolomonoterpenoid alkaloid possessing a 5-fused ring corynanthean type skeleton (Höfle et al. 1980; Zenk & Juenger 2007). Depending on the stereochemistry at the positions C3, C15, C19 and C20, several subgroups of corynanthe alkaloids have been distinguished (Lounasmaa & Kan, 1980). THA belongs to the alloheteroyohimbine subgroup together with rauniticine (Shamma & Richey 1963). Its distribution is restricted to plants belonging to the sole plants of the Apocynaceae, Rubiaceae and Loganiaceae families. THA constitutes the main by-product of the marketed drug raubasine (ajmalicine) industrial production (Poirot 2007; Beziat & Hatinguais 1977; Zsadon et al. 1979). Indeed, this molecule is readily available in a large amount by the reduction with NaBH₄ of serpentine present in the underground parts of Catharanthus roseus (Mandal et al. 1983). This reaction directly carried out on a total alkaloid extract also affords THA resulting from alstonine reduction. Furthermore, this method followed by the isolation of THA and raubasine has been employed for a convenient determination of the alstonine and serpentine respective content in the aerial parts of Catharanthus ovalis (Langlois et al. 1979). The structure of THA has been elucidated after extensive NMR studies during the period 1950–1960 (Wenkert & Roychaudhuri 1957; Wenkert et al. 1961). In the corynanthe series, only the crystal structure of akuammigine (as picrate hydrate) has been previously reported (Laus & Wurst 2008). There have been only a few reports of the THA biological activities (Zou et al. 2010; Sharma et al. 1988). The X-ray data of THA confirmed the relative allo configuration of the C3, C15, C19 and C20 stereocenters. With reference of the known (15S)- configuration due to the biosynthesis, the absolute configuration of the other stereocenters is thus given by (3S, 19S, 20S). The aromatic rings A (C8-C13) and B (C2/C7/C8/C13/N1) are planar. Ring C (C2/C3/N4/C5-C7) adopts a half-chair conformation with N4 above the medium A/B plane by 0.437 (4) Å and C5 below the medium A/B plane by 0.334 (4) Å, respectively. The C/D ring is a trans-fused quinolizidine. Ring D (C3/C14/C15/C20/C21/N4) is a regular chair with H—C3 α axial. The D/E rings are cis-fused; H—C15 and H—C20 are α, the first one being in axial position and the second in equatorial. Ring E (C15-C20) is a half-chair with C19 above the median plan (C15—C16—C17—O18) by -0.273 (5) Å and C20 below the same plan by 0.497 (4) Å. The α Me—C19 group adopts a pseudoequatorial position (Figure 1.). The crystal packing of the compound is governed by one N—H···Cg (π ring, Cg centroid of ring A) interaction and one C—H···Cg (π ring, Cg centroid of ring B) interaction. The crystal cohesion is ensured by intermolecular van der Waals contacts, the shortest is equal to 3.199 (2) Å for O18 and O24.

2. Experimental

The typical conditions used for the semi-synthesis were followed. The pulverized dried roots of Catharanthus roseus (20.0 g) were extracted overnight with a (1:1) mixture of CH₂Cl₂/MeOH. After filtration and solvent removal, the alkaloid extract was dissolved in MeOH and NaBH₄ (500 mg) was slowly added at 0°C. After completion of the reduction (TLC control), water was added and the solution was extracted with CH₂Cl₂ (alkaloids were monitored with the Dragendorff reagent). The combined organic layers were dried over MgSO₄, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (Eluent CH₂Cl₂/MeOH 99/1) to give THA and raubasine as white powders. The former was crystallized from MeOH to give THA as colorless plates suitable for X-ray diffraction.