Bispuupehenone from the South Chinese Sea sponge Dysidea sp

Song Qin; Lei Shi; Jia Li; Yue-Wei Guo

doi:10.1107/S1600536808011987

. 2008 Apr 30;64(Pt 5):o946–o947. doi: 10.1107/S1600536808011987

Bispuupehenone from the South Chinese Sea sponge Dysidea sp.

Song Qin ^a,^*, Lei Shi ^b, Jia Li ^b, Yue-Wei Guo ^a

PMCID: PMC2961175 PMID: 21202427

Abstract

Bispuupehenone, C₄₂H₅₄O₆, formally results from dimerization of puupehenone, which is constructed of sesquiterpene and benzene units. Bispuupehenone was isolated from the South China Sea sponge Dysidea sp. and the single-crystal X-ray diffraction analysis confirmed the previously reported structure. The molecule is located on a twofold axis and the dimerization forms two fused dibenzopyran systems related by symmetry. In the asymmetric unit, the two cyclohexane rings adopt chair conformations, while the two pyran rings adopt half-chair conformations. The relative stereochemistry and configurations for the ring junctions are in agreement with the structure reported previously.

Related literature

The title compound was first isolated from the Pacific marine sponge Heteronema sp., see Amade et al. (1983 ▶). For the biological and pharmaceutical activity of puupehenone, see: Barrero et al. (1998 ▶, 1999 ▶); Castro et al. (2004 ▶); Ciavatta et al. (2007 ▶); Longley et al. (1993 ▶); Kohmoto et al. (1987 ▶); Takamatsu et al. (2003 ▶). For the synthesis and semi-synthesis of puupehenone and its derivatives, see: Hamann (2003 ▶); Alvarez-Manzaneda et al. (2005 ▶, 2007 ▶).

Experimental

Crystal data

C₄₂H₅₄O₆
M _r = 654.85
Tetragonal,
a = 13.5981 (10) Å
c = 18.7260 (19) Å
V = 3462.6 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 293 (2) K
0.39 × 0.24 × 0.14 mm

Data collection

Bruker APEX CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2000 ▶) T _min = 0.743, T _max = 0.990
20532 measured reflections
2219 independent reflections
1644 reflections with I > 2σ(I)
R _int = 0.110

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.113
S = 0.94
2219 reflections
225 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: SMART (Bruker, 2000 ▶); cell refinement: SAINT (Bruker, 2000 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808011987/bh2164sup1.cif

e-64-0o946-sup1.cif^{(21.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808011987/bh2164Isup2.hkl

e-64-0o946-Isup2.hkl^{(106.9KB, hkl)}

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

Acknowledgments

The research work was financially supported by the National Marine ‘863’ Project (No. 2006 A A09Z412), the Natural Science Foundation of China (Nos. 3073108, 20772136, and 20721003), CAS Key Project (grant KSCX2-YW-R-18) and STCSM Projects (No. 017XD14036 and 06DZ22028), and partially funded by a grant from the Syngenta-SIMM-PhD Studentship Project.

supplementary crystallographic information

Comment

Bispuupehenone (I) was firstly isolated from Pacific marine sponge Heteronema sp. (Amade et al., 1983), and was considered to be generated from co-occurring puupehenone (II) (Fig. 1) by in vitro oxidative coupling. The benzopyrane structure for the dimer is deduced by the comparison of its UV spectrum data with those of a simple dibenzofuran and a simple benzopyran. Although compound (II) and its derivatives have been reported to display a wide range of important biological activities, including antiviral, antifungal, antimalarial, and antitumor activities (Barrero et al., 1998, 1999; Longley et al., 1993; Castro et al., 2004; Ciavatta et al., 2007; Kohmoto et al., 1987; Takamatsu et al., 2003), the biological properties of (I) have been seldom reported. Synthesis and semi-synthesis of puupehenone and its derivatives have been published (Hamann, 2003); Alvarez-Manzaneda et al., 2005, 2007).

As part of our research project on the study of the South China Sea marine organisms, a sample of the sponge Dysidea sp. was collected off the Lingshui Bay, Hainan Province, China, and was chemically investigated. Bispuupehenone, (I), was isolated and crystallized from the Et₂O-soluble fraction of the acetone extract of the animal, and the structure of (I) was firstly elucidated by spectroscopic methods, NMR, UV and MS, and eventually confirmed through X-ray diffraction analysis. Herein, we report the X-ray structure of (I).

The projection of bispuupehenone is shown in Figure 2. In the structure, two puupehenone moieties are connected through two O atoms and a C—C bond between benzene rings, forming a benzopyran moiety at the midpoint of the axial symmetric molecule. Rings A and B of (I) are in chair conformations, while rings C and D adopt half-chair conformations. Moreover, the trans junction between rings A/B and the cis junction between rings B/C are in agreement with the structure reported previously.

Bispuupehenone was tested for the inhibitory activities against hPTP1B (human protein tyrosine phosphatase 1B), a key target for the treatment of Type-II diabetes and obesity, and showed excellent inhibitory effect with IC₅₀ value of 0.98 mg ml^-1. Other bioassays, such as antibacterial and anti-inflammatory, are currently ongoing.

Experimental

The specimens of sponge were collected from Lingshui Bay, Hainan Province, China, in July 2004, and identified as Dysidea sp. by Professor J.-H. Li of the Institute of Oceanology, Chinese Academy of Sciences. A voucher specimen (LS-210) is available for inspection at the Herbarium of Shanghai Institute of Materia Medica, CAS. The frozen animals (dry weight 96.3 g) were cut into small pieces and exhaustively extracted with acetone (3×3 L). The organic extract was evaporated to give a residue, which was partitioned between Et₂O and H₂O. The Et₂O solution was concentrated under reduced pressure to give a dark brown residue (4.7 g), which was fractionated by gradient silica gel column chromatography [0–100% acetone in light petroleum ether (PE)], yielding seven fractions (A···G). The fraction C eluted by PE/Me₂CO (95:5) was further purified on a second silica gel column chromatography eluting with PE—Et₂O (90:10) to afford (I) (14.3 mg). Crystals suitable for X-ray analysis were obtained by slow evaporation from a chloroform solution.