(1S,5R,7R,30S)-14-De­oxy­isogarcinol

Ranjeet Kaur; Prema G Vasudev; Sunil K Chattopadhyay

doi:10.1107/S1600536812020788

. 2012 May 23;68(Pt 6):o1861–o1862. doi: 10.1107/S1600536812020788

(1S,5R,7R,30S)-14-Deoxyisogarcinol

Ranjeet Kaur ^a, Prema G Vasudev ^b,^*, Sunil K Chattopadhyay ^a

PMCID: PMC3379428 PMID: 22719626

Abstract

The title compound, C₃₈H₅₀O₅ {systematic name: 10-(3-hydroxybenzoyl)-2,2,7,7-tetramethyl-3,6,8-tris(3-methylbut-2-enyl)-3,4,4a,5,6,7-hexahydro-4a,8-methano-2H-cycloocta[b]pyran-9,11(8H)-dione}, is a polyisoprenylated benzophenone, isolated for the first time from the fruits of Garcinia indica during our investigation of bioactive compounds from this plant and their large-scale extraction. The relative configuration of the title compound was chosen based on comparison of its spectroscopic and optical rotation data with that of the isomorphous and isostructural compound isogarcinol, whose absolute configuration is known. The crystal packing features O—H⋯O hydrogen bonds. A Cambridge Structural Database analysis revealed that the crystal structure reported here is isomorphous and isostructural with that of isogarcinol.

Related literature

For background information on the plant Garcinia indica and its biologically active compounds, see: Anonymous (1956 ▶); Padhye et al. (2009 ▶); Jayaprakasha & Sakariah (2002 ▶); Yamaguchi et al. (2000a ▶,b ▶); Sang et al. (2001 ▶). For related compounds, see: Krishnamurthy et al. (1981 ▶, 1982 ▶); Rao et al. (1980a ▶,b ▶); Sahu et al. (1989 ▶); Marti et al. (2009 ▶). For the isolation, purification and spectroscopic study of the title compound, see: Kaur et al. (2012 ▶). For a description of the Cambridge Structural Database, see: Allen (2002 ▶). For the determination of absolute configuration, see: Flack (1983 ▶); Hooft et al. (2008 ▶).

Experimental

Crystal data

C₃₈H₅₀O₅
M _r = 586.78
Orthorhombic,
a = 11.561 (5) Å
b = 14.657 (7) Å
c = 20.457 (10) Å
V = 3466 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 293 K
0.38 × 0.24 × 0.14 mm

Data collection

Bruker SMART APEX CCD diffractometer
22425 measured reflections
4711 independent reflections
2083 reflections with I > 2σ(I)
R _int = 0.119

Refinement

R[F ² > 2σ(F ²)] = 0.068
wR(F ²) = 0.246
S = 0.96
4711 reflections
395 parameters
H-atom parameters constrained
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Data collection: SMART (Bruker, 2003 ▶); cell refinement: SAINT (Bruker, 2003 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶)and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812020788/nr2023sup1.cif

e-68-o1861-sup1.cif^{(39.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812020788/nr2023Isup2.hkl

e-68-o1861-Isup2.hkl^{(230.8KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812020788/nr2023Isup4.cdx

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
O5—H5⋯O1ⁱ	0.82	2.05	2.785 (6)	150

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Symmetry code: (i) Inline graphic .

Acknowledgments

The X-ray diffraction facility at the IIT, Kanpur, is acknowledged.

supplementary crystallographic information

Comment

Garcinia indica (family: Guttiferae, Genus: Garcinia) is a slender evergreen tree with drooping branches, which is well known for its culinary, pharmaceutical and industrial uses. The fruits of Garcinia indica are anthelmintic, cardiotonic and useful in piles, dysentery, tumors, pains and heart complaints (Anonymous, 1956). The dried fruit rind of G. indica is traditionally used as a garnish for curry. Kokum butter (oil from the seeds of Garcinia indica) is extracted from the seeds and used in the cosmetic industry for preparing lotions, creams, lip balms and soaps (Padhye et al., 2009). The fruit rind extract of G. indica contains polyisoprenylated benzophenone derivatives namely garcinol, isogarcinol, xanthochymol, isoxanthochymol and organic acids, chiefly (-)-hydroxycitric acid (Jayaprakasha et al. 2002). Garcinol has shown promising antioxidative, antiglycation, anticancer, anti HIV, anti ulcer and free radical scavenging activities (Yamaguchi et al. 2000a; 2000b; Padhye et al., 2009). Isogarcinol has also shown biological activities similar to that of garcinol and has been claimed to be anti-inflammatory, antitumor, lipase inhibitor, antiobesity agent and antiulcer agent (Sang et al., 2001). In order to study the detailed biological activities of isogarcinol and garcinol (Figure 1), we have developed a process technology for large scale extraction and isolation of the two molecules in good quantities from 7 kg fruits of G. indica. During this process, we have been able to isolate two new minor compounds from the fruit rind, in addition to garcinol and isogarcinol. These were identified as 14-deoxyisogarcinol (1) and a polyprenylated acylphloroglucinol derivative (2) (Figure 1) by detailed spectral analysis (Kaur et al., 2012) and comparison with literature data (Krishnamurthy et al., 1981 and 1982; Rao et al., 1980a and 1980b; Sahu et al., 1989). Compound 1 and 2 were reported for the first time from the fruits of G. indica.

The slow solvent evaporation of a pure fraction of 1 from acetone yielded rectangular shaped transparent single crystals, providing us an opportunity to confirm its molecular conformation. The relative configuration of 1 determined in crystals is shown in Figure 2a. The molecule crystallized in orthorhombic space group P2₁2₁2₁, with one molecule in the asymmetric unit. Earlier, a detailed spectroscopic study of 1 has been carried out (Kaur et al., 2012) which indicated that the structure of 1 is closely comparable to that of isogarcinol, whose absolute configuration has been experimentally determined (Krishnamurthy et al., 1982, Marti et al., 2009) as 1S,5R,7R,30S. In the present study, since there are no heavier atoms than O, no attempt was made to determine the absolute configuration of 1. However, between the two enantiomeric possibilities in the crystal structure, the relative (absolute) configuration at chiral centres C1, C5, C7 and C30 were chosen same as that of isogarcinol (S, R, R, S, respectively) taking into consideration the closely related NMR data and optical rotation of 1 and isogarcinol.In the bicyclic system, the C1—C9 bond is in beta and the isoprenyl group at C7 is in alpha orientation. Furthermore, the ketonic group at C9 and the phenol moiety lies on the same side of a plane defined by atoms C1—C2—C3—C4—C5. A comparison of the crystal state conformation of 1 determined in this study with that of isogracinol (Krishnamurthy et al., 1982; Marti et al., 2009) revealed that they are identical. A superposition of the two molecules resulted in an RMSD of 0.02 Å, illustrating this fact (Figure 2 b). In addition, the unit-cell dimensions of 1 (a=11.56 Å, b=14.66 Å, c=20.46 Å) are very similar to that of isogarcinol (a=11.88 Å, b=14.71 Å, c=20.58 Å). This prompted us to compare the crystal packing in both the cases. As isogarcinol has an additional hydrogen bond donor at C14, a different packing arrangement could be anticipated. The intermolecular hydrogen bonds observed in the crystals structure of 1 and isogarcinol (CSD refcode BEVHIT01; Marti et al., 2009) are illustrated in Figure 3 and a comparison of hydrogen bond parameters in both the crystals are given in Table 2. A view of the packing of molecules in the unit cell of 1 and isogarcinol is shown in Figure 4. Interestingly, both the compounds display exactly similar packing arrangement in crystals. The hydroxyl group at C13 is hydrogen bonded to the carbonyl oxygen at C9 of a molecule related by the 2-fold screw along the crystallographic a axis, in both the crystals. In the case of isogarcinol, this arrangement makes the additional hydroxyl group at C14 close to the oxygen atom attached to C13 of the same symmetry related molecule, resulting in an O—H···O hydrogen bond.

A survey of the available crystal structures of isogarcinol and its derivatives in the Cambridge Structural Database (CSD, Version 5.32, Allen, 2002) resulted in three structures; isogarcinol (CSD refcode BEVHIT01; Marti et al., 2009), 14-methoxyisogarcinol (CSD refcode JISXEP; Marti et al., 2009), and 13,14-bis(bromobenzenesulfonyl) isogarcinol (CSD refcode YOMMIX; Marti et al., 2009). Isogarcinol and its 14-methoxy derivative crystallized in the space group P2₁2₁2₁ and the 13,14-bis(bromobenzenesulfonyl) derivative crystallized in the monoclinic space group P2₁. The latter does not have a potential hydrogen bond donor, and has a different packing arrangement as compared to the other two. The 14-methoxy derivative and 1 have only one hydrogen bond donor, which is at C13. The major structural differences between these two structures are in the orientations of the aromatic ring and the isoprenyl group at C7 (Figure 5). The aromatic ring in JISXEP has flipped approximately 180° about the C10—C11 bond (dihedral angle C9—C10—C11—C12 = 3° in 1, and -171° in JISXEP). This has resulted in a longer O5···O1 (x + 1/2, -y + 1/2, -z) distance in JISXEP (3.46 Å). The corresponding H5···O1 distance is 3.02 Å and the angle O5—H5···O1 is 116°, suggesting that this interaction is very weak in JISXEP as compared to the hydrogen bond interactions in the crystals of 1 and isogarcinol. The aromatic rings of 2₁-screw related molecules along the crystallographic a axis align almost parallel to each other in the case of 1 and isogarcinol (angle between the aromatic planes are 8° and 5.4°, respectively) while in the JISXEP they are inclined at an angle of 35°. These conformational differences between the two derivatives lead to differences in the intermolecular contacts. On the other hand, 1 and isogarcinol are isostructural.

Experimental

Isolation of 1 and crystallization: Isolation of 1 from the crude fruit rind extract of G. indica is as reported elsewhere (Kaur et al., 2012). After isolation, the pure compound 1 (m.p. 235 °C) was re-dissolved in acetone and slow evaporation of the solvent yielded rectangular crystals.