1-(1-Hy­droxy­eth­yl)-7,8-dihydro­indolo[2,3-a]pyridine­[3,4-g]quinolizin-5(13H)-one (angustoline) monohydrate from Nauclea subdita (Rubiaceae)

Sook Yee Liew; Mat Ropi Mukhtar; Khalijah Awang; Mohd Rais Mustafa; Seik Weng Ng

doi:10.1107/S1600536811022768

. 2011 Jun 18;67(Pt 7):o1727–o1728. doi: 10.1107/S1600536811022768

1-(1-Hydroxyethyl)-7,8-dihydroindolo[2,3-a]pyridine[3,4-g]quinolizin-5(13H)-one (angustoline) monohydrate from Nauclea subdita (Rubiaceae)

Sook Yee Liew ^a, Mat Ropi Mukhtar ^a, Khalijah Awang ^a, Mohd Rais Mustafa ^b, Seik Weng Ng ^a,^*

PMCID: PMC3151776 PMID: 21837117

Abstract

The title compound (trivial name: angustoline monohydrate), C₂₀H₁₇N₃O₂·H₂O, features a fused-ring system formed by one five- and four six-membered rings. The nearly planar benzimidazole portion (r.m.s. deviation = 0.008 Å) and the nearly planar 2,7-naphthyridin-1-one portion (r.m.s. deviation = 0.022 Å) of the fused-ring system are slightly twisted, with a dihedral angle of 9.47 (8)°, owing to the tetrahedral nature of the two methylene linkages in the central six-membered ring. The secondary N atom acts as a hydrogen-bond donor to the water molecule of crystallization. In the crystal, the amino and hydroxy groups, and the water molecule are engaged in hydrogen bonding, generating a three-dimensional network.

Related literature

For the isolation of the title compound from other plants, see: Abreu & Pereira (1998 ▶, 2001 ▶); Au et al. (1973 ▶); Carte et al. (1990 ▶); Erdelmeier et al. (1992 ▶); Fan et al. (2010 ▶); Hotellier et al. (1975 ▶); Kakuguchi et al. (2009 ▶); Lin et al. (1988 ▶); Sun et al. (2008 ▶); Xuan et al. (2007 ▶); Zeches et al. (1985 ▶).

Experimental

Crystal data

C₂₀H₁₇N₃O₂·H₂O
M _r = 349.38
Monoclinic,
a = 8.8350 (3) Å
b = 6.7002 (2) Å
c = 14.7347 (4) Å
β = 103.117 (3)°
V = 849.48 (4) Å³
Z = 2
Cu Kα radiation
μ = 0.76 mm⁻¹
T = 100 K
0.30 × 0.03 × 0.03 mm

Data collection

Agilent SuperNova Dual with an Atlas detector diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010 ▶) T _min = 0.803, T _max = 0.978
6453 measured reflections
3252 independent reflections
3015 reflections with I > 2σ(I)
R _int = 0.027

Refinement

R[F ² > 2σ(F ²)] = 0.036
wR(F ²) = 0.098
S = 1.02
3252 reflections
251 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.23 e Å⁻³
Absolute structure: Flack (1983 ▶), 1395 Friedel pairs
Flack parameter: 0.1 (2)

Data collection: CrysAlis PRO (Agilent, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: X-SEED (Barbour, 2001 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811022768/xu5242sup1.cif

e-67-o1727-sup1.cif^{(20.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811022768/xu5242Isup2.hkl

e-67-o1727-Isup2.hkl^{(159.5KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯N3ⁱ	0.97 (4)	1.77 (4)	2.732 (2)	171 (3)
O1w—H11⋯O1ⁱⁱ	0.85 (4)	2.08 (4)	2.928 (2)	169 (3)
O1w—H12⋯O2ⁱⁱⁱ	0.83 (4)	1.95 (4)	2.762 (2)	167 (3)
N1—H1⋯O1w	0.85 (3)	2.02 (3)	2.861 (2)	177 (2)

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

Acknowledgments

This work was carried under the aegis of a University of Malaya–CNRS (France) collaborative framework. We thank the Ministry of Higher Education (grant No. FRGS-FP016/2010 A) for financial support.

supplementary crystallographic information

Comment

The alkaloid angustoline has been isolated from a number of plants: Camptotheca acuminata (Carte et al., 1990; Lin et al., 1988), Nauclea latifolia (Kakuguchi et al., 2009; Hotellier et al., 1975), Nauclea officinalis (Fan et al., 2010; Sun et al., 2008; Xuan et al., 2007), Nauclea orientalis (Erdelmeier et al., 1992), Nauclea pobeguinii (Zeches et al., 1985), Sarcocephalus latifolius (Abreu & Pereira, 1998; 2001) and Strychnos angustiflora (Au et al., 1973).

The alkaloid is isolated in the crystalline form as a monohydrate (Scheme I). The planar benzimidazole portion and the planar 2,7-naphthyridin-1-one portion of the fused-ring system are slightly twisted [dihedral angle 9.47 (8)°] owing to the tetrahedral nature of the two methylene linkages (Fig. 1). The secondary N atom is hydrogen-bond donor to the water molecule. The amino and hydroxy groups, and the lattice water molecule are engaged in hydrogen bonding to furnish a three-dimensional network (Table 1).

Experimental

Nauclea subdita (Rubiaceae) was collected from Bukit Kinta forest reserve, Chemor, Perak, Malaysia, and specimens were deposited at the Herbarium, Department of Chemistry, University of Malaya.

Dried and ground bark of Nauclea subdita (1.7 kg) was extracted with hexane (17 L) for 3 days. The hexane extract was concentrated under reduced pressure. The dried plant material was soaked in ammonium hydroxide for 2 h. It was further extracted with dichloromethane (17 L) for 3 days. The dichloromethane extract was concentrated under reduced pressure to give a crude alkaloid (7.1 g). A portion (6.0 g) was subjected to column chromatography on silica gel 60 GF₂₅₄ by using a step gradient of dichloromethane and methanol. One of the fractions when further purified by using dichloromethane/methanol (95:5) afforded the pure compound, whose formulation was established by NMR spectroscopic analysis.