(1S*,4′S*,5R*)-1-Isopropyl-5-meth­oxy-2′,3-dimethyl-4,6-dioxa-2-aza­spiro­[bicyclo­[3.2.0]hept-2-ene-7,4′-isoquinoline]-1′,3′(2′H,4′H)-dione

Hoong-Kun Fun; Ching Kheng Quah; Chengmei Huang; Haitao Yu

doi:10.1107/S1600536811015315

. 2011 Apr 29;67(Pt 5):o1271–o1272. doi: 10.1107/S1600536811015315

(1S,4′S,5R*)-1-Isopropyl-5-methoxy-2′,3-dimethyl-4,6-dioxa-2-azaspiro[bicyclo[3.2.0]hept-2-ene-7,4′-isoquinoline]-1′,3′(2′H,4′H)-dione

Hoong-Kun Fun ^a,^*,^‡, Ching Kheng Quah ^a,^§, Chengmei Huang ^b, Haitao Yu ^b

PMCID: PMC3089152 PMID: 21754556

Abstract

In the isoquinoline ring system of the title molecule, C₁₈H₂₀N₂O₅, the N-heterocyclic ring is in a half-boat conformation. The dioxa-2-azaspiro ring is essentially planar, with a maximum deviation of 0.029 (1) Å, and makes a dihedral angle of 30.63 (5)° with the benzene ring. The molecular structure is stabilized by a weak intramolecular C—H⋯O hydrogen bond, which generates a S(6) ring motif. In the crystal, molecules are linked via weak intermolecular C—H⋯O hydrogen bonds into a three-dimensional supramolecular network. Additional stabilization is provided by π–π stacking interactions between symmetry-related benzene rings with a centroid–centroid distance of 3.6507 (5) Å.

Related literature

For general background to and the potential biological activity of the title compound, see: Pollers-Wieers et al. (1981 ▶); Malamas et al. (1994 ▶); Yu et al. (2010 ▶); Du et al. (2008 ▶); Chen et al. (2006 ▶); Zhang et al. (2006 ▶); Mitchell et al. (1995 ▶, 2000 ▶); Harris et al. (2005 ▶); Wang et al. (2010 ▶); Huang et al. (2011 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶). For standard bond-length data, see: Allen et al. (1987 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For ring conformations, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₈H₂₀N₂O₅
M _r = 344.36
Monoclinic,
a = 10.5721 (2) Å
b = 10.4260 (2) Å
c = 15.7633 (3) Å
β = 101.641 (1)°
V = 1701.77 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.51 × 0.37 × 0.35 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.951, T _max = 0.966
23124 measured reflections
6242 independent reflections
5286 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.108
S = 1.02
6242 reflections
231 parameters
H-atom parameters constrained
Δρ_max = 0.49 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811015315/lh5237sup1.cif

e-67-o1271-sup1.cif^{(22.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811015315/lh5237Isup2.hkl

e-67-o1271-Isup2.hkl^{(305.6KB, 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
C6—H6A⋯O2ⁱ	0.93	2.59	3.3754 (12)	143
C15—H15A⋯O5	0.96	2.56	3.2151 (12)	126
C18—H18A⋯O1ⁱⁱ	0.96	2.58	3.4298 (13)	148
C18—H18C⋯O2ⁱⁱⁱ	0.96	2.58	3.3641 (12)	139

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

Acknowledgments

HKF and CKQ thank Universiti Sains Malaysia for the Research University Grant (No. 1001/PFIZIK/811160). Financial support from the National Science Foundation of China (20972067) is also acknowledged.

supplementary crystallographic information

Comment

Isoquinolines are often found in bioactive natural products. They have been used to build blocks of benzo[c]phenanthridine alkaloids (Pollers-Wieers et al., 1981; Malamas et al., 1994; Yu et al., 2010). Isoquinoline-1,3,4-trione derivatives were reported to be a type of small molecular inhibitor against caspase-3 which can promote apoptosis of the cells (Du et al., 2008; Chen et al., 2006). They can also attenuate apoptosis of neuronal cells induced by β-amyloid.(Zhang et al., 2006). Isoquinoline-1,3,4-trione and its derivatives have been reported to be redox mediators of photosystems and have been used as herbicides (Mitchell et al., 2000; 1995). Oxazole rings are also found in some bioactive natural products such as Annuloline and Ostreogrycin A. Oxazoles can be used to inhibit the activity of malignant tumors (Harris et al., 2005). Since a lot of natural products especially the alkaloids containing the isoquinoline or oxazole ring are bioactive, there has been intense development of methodology to construct such moieties (Wang et al., 2010). The title compound which was derived from isoquinoline-1,3,4-trione and oxazoles (Huang et al., 2011) may have potential use in biochemical and pharmaceutical fields. Due to the importance of the isoquinoline-1,3,4-trione derivatives, we report herein the crystal structure of the title compound with a relative configuration of (1S^*, 4'S^*, 5R^*).

In the title racemic compound, Fig. 1, atoms C9, C10 and C12 are the chiral centers. The isoquinoline ring system (N1/C1-C9) is not completely planar, the N-heterocyclic ring (N1/C1-C3/C8/C9) being distorted towards a half-boat conformation with atom C1 deviating by 0.243 (1) Å from the mean plane through the remaining atoms, puckering parameters (Cremer & Pople, 1975) Q = 0.2843 (9) Å, Θ = 64.10 (18)° and φ =100.97 (19)°. The dioxa-2-azaspiro ring (N2/O4/C10-C12) is essentially planar [maximum deviation of 0.029 (1) Å at atoms O4 and C10] and it inclines at a dihedral angle of 30.63 (5)° with the benzene ring (C3-C8). Bond lengths (Allen et al., 1987) and angles are within normal ranges. The molecular structure is stabilized by a weak intramolecular C15–H15A···O5 hydrogen bond (Table 1) which generates a S(6) ring motif (Fig. 1, Bernstein et al., 1995).

In the crystal structure, Fig. 2, molecules are linked via intermolecular C6–H6A···O2ⁱ, C18–H18A···O1ⁱⁱ and C18–H18C···O2ⁱⁱⁱ hydrogen bonds (Table 1) into a three-dimensional supramolecular network. The crystal packing is further consolidated by π–π stacking interactions between the centroids of the C3-C8 (Cg1) rings, with a Cg1···Cg1^iv distance of 3.6507 (5) Å [symmetry code: (iv) 1-x, 1-y, -z].

Experimental

The title compound was the main product from the photoreaction between isoquinoline-1,3,4-trione and 4-isopropyl-5-methoxy-2-methyloxazole. The compound was purified by flash column chromatography with ethyl acetate/petroleum ether (1:4) as eluents. X-ray quality crystals of the title compound was obtained from slow evaporation of an acetone and petroleum ether solution (1:5) (m.p. 451-453 K).