(4R*,4aR*,7aS*)-5-Oxo-6-phenyl-4a,5,6,7,7a,8-hexa­hydro-4H-furo[2,3-f]isoindole-4-carb­oxy­lic acid

Yuriy I Horak; Roman Z Lytvyn; Fedor I Zubkov; Eugeniya V Nikitina; Yuriy V Homza; Tadeusz Lis; Vasyl Kinzhybalo; Mykola D Obushak

doi:10.1107/S160053681300144X

. 2013 Jan 23;69(Pt 2):o273–o274. doi: 10.1107/S160053681300144X

(4R,4aR,7aS*)-5-Oxo-6-phenyl-4a,5,6,7,7a,8-hexahydro-4H-furo[2,3-f]isoindole-4-carboxylic acid

Yuriy I Horak ^a,^*, Roman Z Lytvyn ^a, Fedor I Zubkov ^b, Eugeniya V Nikitina ^b, Yuriy V Homza ^a, Tadeusz Lis ^c, Vasyl Kinzhybalo ^d, Mykola D Obushak ^a

PMCID: PMC3569801 PMID: 23424547

Abstract

The asymmetric unit of the title compound, C₁₇H₁₅NO₄, contains two independent molecules with similar geometric parameters. In both molecules, the conformation of the cyclohexene ring is half-chair, while the pyrrolidinone ring adopts an envelope conformation with the γ-carbon atom of the α-pyrrolidinone ring as the flap. In the crystal, O—H⋯O hydrogen bonds between the carboxylic and carbonyl groups link alternate independent molecules into chains propagating in the b-axis direction. The crystal packing also features weak C—H⋯π interactions.

Related literature

For the intramolecular Diels–Alder reaction of vinylfuranes, see: Patre et al. (2007 ▶). For related solid-phase Diels–Alder reaction with vinyl benzenes, see: Sun et al. (2000 ▶). For palladium-catalysed tandem cyclization of allenes with heteroarylhalides, see: Ohno et al. (2005 ▶). For heterolignan derivatives, see: Ramos et al. (1999 ▶); Leteurtre et al. (1992 ▶) and for their pharmaceutical properties, see: Iwasaki et al. (1996 ▶); Ducharme et al. (1994 ▶). For a related structure, see: Obushak et al. (2011 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₇H₁₅NO₄
M _r = 297.30
Orthorhombic,
a = 12.107 (4) Å
b = 16.945 (5) Å
c = 27.370 (9) Å
V = 5615 (3) Å³
Z = 16
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 120 K
0.64 × 0.42 × 0.28 mm

Data collection

Kuma KM-4-CCD diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006 ▶) T _min = 0.972, T _max = 1.000
84648 measured reflections
13130 independent reflections
9304 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.127
S = 1.03
13130 reflections
399 parameters
H-atom parameters constrained
Δρ_max = 0.54 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2006 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2006 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Click here for additional data file.^{(30KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S160053681300144X/cv5382sup1.cif

e-69-0o273-sup1.cif^{(30KB, cif)}

Click here for additional data file.^{(642KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681300144X/cv5382Isup2.hkl

e-69-0o273-Isup2.hkl^{(642KB, hkl)}

Click here for additional data file.^{(2.8KB, cdx)}

Supplementary material file. DOI: 10.1107/S160053681300144X/cv5382Isup3.cdx

Click here for additional data file.^{(6KB, cml)}

Supplementary material file. DOI: 10.1107/S160053681300144X/cv5382Isup4.cml

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

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

Cg1 and Cg2 are the centroids of the C13A–C18A and O1A–C5A rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3B—H3B1⋯O4A	0.84	1.83	2.6517 (11)	165
O3A—H3A1⋯O4B ⁱ	0.84	1.79	2.6329 (10)	178
C8A—H8A⋯Cg1ⁱⁱ	1.00	2.50	3.4710 (14)	165
C15A—H15A⋯Cg2ⁱⁱⁱ	0.95	2.63	3.5470 (15)	162
C18A—H18B⋯Cg2^iv	0.99	2.72	3.5492 (14)	141

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

Acknowledgments

The authors are grateful to the Ukrainian State Fund for Fundamental Research (grant No. F40.3/045) and the Russian Foundation for Basic Research (grant No. 11–03-90416) for the financial support of this work.

supplementary crystallographic information

Comment

Recently, the researchers attention was drawn to such class of compounds as heterolignans (Figure 1) (Ramos et al., 1999). The best known heterolignan is azatoxin, which has antineoplastic activity (Leteurtre et al., 1992). In addition, it should be noted that a number heterolignans show anticancer, antirheumatic and antiasthmatic activity (Iwasaki et al., 1996; Ducharme et al., 1994). There are two important aspects of the synthesis of these compounds. First, as biological activity investigations have shown, the replacement of carbon atoms by heteroatoms in the cycle, or the replacement of benzene fragments by heterocycles, has little effect on biological activity. Second, from the synthetic point of view C–heteroatom bonds are easier accesible than C–C bonds. In addition to this, structural variability and synthetic availability of heterocycles are significantly higher than benzene fragments.

Considering mentioned above, synthesis of lignan analogues or their synthetic precursors, including those with furan cycles, are contemporary tasks. It was found that in the reaction of maleic anhydride and [3-(2-furyl)-2-propenyl]-phenylamine the furane cycle persists and exocyclic double bond reacts. Furoisoindole system with carboxyl group in the six-membered ring is formed. It should be noted that earlier furoisoindole system used to be obtained by the Domino Wittig-Diels-Alder reaction (Patre et al., 2007) and palladium-catalyzed tandem cyclization of allenes with heteroarylhalides (Ohno et al., 2005).

Crystal structure of title compound consists of two independent molecules with very similar geometrical parameters (Figure 2). The five-membered C7—C8—C11—N1—C18 rings of both independent A and B molecules adopt envelope conformation puckered on C7 [puckering parameters (Cremer & Pople, 1975): q₂ = 0.3449 (8) and 0.3525 (9) Å, φ₂ = 283.66 (13) and 287.71 (14)° for A and B molecules, respectively]. The six-membered C4—C5—C6—C7—C8—C9 rings of both independent A and B molecules adopt half-chair conformation (Q = 0.5113 (8) and 0.5190 (9) Å, θ = 130.33 (9) and 129.98 (10)°, φ = 31.02 (12) and 25.34 (13)° for A and B molecules, respectively). There are three chiral carbon atoms (C7, C8 and C9) in the molecule. Two independent molecules are of the same chirality. Since, the compound crystalizes in centrosymmetric space group, it consists of 1:1 ratio mixture of S,R,R- and R,S,S-isomers.

The structure displays O—H···O hydrogen bonding between acid carboxyl and carbonyl groups, which connects molecules into chains propagating in b-axis direction (Figure 3). The crystal packing exhibits weak intermolecular C—H···π interactions.

Experimental

To a solution of 0.003 mol [3-(2-furyl)-2-propenyl]-phenylamine in benzene 0.003 mol of grinded into a powder maleic anhydride was added. The mixture was boiled until the precipitation of sediment (6–7 h) and 3–4 h thereafter. The precipitate was filtered, washed with benzene and alcohol and recrystalized from EtOH/DMF/H₂O.