(3R*)-Methyl 3-[(2S*)-4,6-dimethoxy-2-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1-benzofuran-2-yl]-2-methoxycarbonyl-3-phenylpropionate

Xian-You Wang; Nan Li; Yong-Qiang Ma; Zhao-Hai Qin

doi:10.1107/S1600536809042196

. 2009 Oct 28;65(Pt 11):o2893. doi: 10.1107/S1600536809042196

(3R)-Methyl 3-[(2S)-4,6-dimethoxy-2-(4-methoxyphenyl)-3-oxo-2,3-dihydro-1-benzofuran-2-yl]-2-methoxycarbonyl-3-phenylpropionate

Xian-You Wang ^a, Nan Li ^a, Yong-Qiang Ma ^a, Zhao-Hai Qin ^a,^*

PMCID: PMC2971057 PMID: 21578476

Abstract

The title compound, C₂₉H₂₈O₉, was isolated from the reaction of 4,6-dimethoxy-2-(4-methoxyphenyl)-3-benzofuran and α-methoxycarbonylcinnaminate. The two aromatic rings form a dihedral angle of 22.7 (1)°. One methoxycarbonyl group is disordered between two orientations in a 0.612 (4):0.388 (4) ratio. The crystal structure exhibits no significantly short intermolecular contacts.

Related literature

The title compound is a key intermediate in the synthesis of rocaglamide, see: Kraus & Sy (1989 ▶); Li et al. (2008 ▶). For the biological activity of rocaglamide derivatives, see: Zhu et al. (2007 ▶).

Experimental

Crystal data

C₂₉H₂₈O₉
M _r = 520.51
Triclinic,
a = 6.901 (5) Å
b = 10.478 (5) Å
c = 18.467 (5) Å
α = 79.838 (5)°
β = 86.976 (5)°
γ = 77.097 (5)°
V = 1281.1 (12) Å³
Z = 2
Cu Kα radiation
μ = 0.84 mm⁻¹
T = 295 K
0.40 × 0.36 × 0.34 mm

Data collection

Oxford Diffraction Gemini S Ultra diffractometer
Absorption correction: multi-scan (CrysAlis Pro; Oxford Diffraction, 2009 ▶). T _min = 0.731, T _max = 0.764
24595 measured reflections
4811 independent reflections
4581 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.093
S = 1.01
4811 reflections
378 parameters
9 restraints
H-atom parameters constrained
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.45 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2009 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809042196/cv2618sup1.cif

e-65-o2893-sup1.cif^{(26.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809042196/cv2618Isup2.hkl

e-65-o2893-Isup2.hkl^{(230.9KB, hkl)}

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

Acknowledgments

We acknowledge financial support of this investigation by the National Natural Science Foundation of China (grant No. 20772151).

supplementary crystallographic information

Comment

Rocaglamide (Fig. 1), featuring a cyclopenta[b]benzofuran ring system, was first isolated from the roots and stems of Aglia elliptifolia by King and co-workers in 1982. Since then, rocaglamide and related compounds have shown cytostatic and cytotoxic activity against a variety of human cancer cell lines (King et al., 1982; Zhu et al., 2007). The structural complexity of rocaglamide and its significant activity make it an attractive synthetic target. To date, several synthetic routes were developed for rocaglamide and its derivatives (Kraus et al., 1989; Li et al., 2008).

The title compound (I) is one of the key intermediates to rocaglamide in Li's strategy (Li et al., 2008). Preparation of the compound involved the reaction of 4,6-dimethoxy-2-(4-methoxyphenyl)-3-benzofuran, α-methoxycarbonylcinnaminate and Triton B (N,N,N-trimethylbenzylammonium hydroxide) for 4 h with concomitant stirring in 40 °C and purification by silica-gel column chromatography (petroleumether/EtOAc, 3:1) to give colourless crystals.

In (I) (Fig. 2), two aromatic rings form a dihedral angle of 22.7 (1) °, and one methoxycarbonyl group is disordered between two orientations in an approximate ratio 3:2. The X-ray crystal structure confirms that the substance produced is a racemic mixture of Methyl 2-methoxycarbonyl-(3R, 4S) - and - (3S, 4R) - 4-(4, 6-dimethoxy-3-oxo -2, 3-dihydrobenzofuran-2-yl]-4-(4-methoxy-phenyl)-3-phenylpropionate as predicted by NOESY NMR experiments.

Experimental

Under N₂ atmosphere, to asolution of 4, 6-dimethoxy- 2-(4-methoxyphenyl)-3- benzofuran (3.0 g, 10 mmol) in anhydrous THF (100 ml) was added a solution of Triton B (40% in CH₃OH, 0.3 ml) and a solution of α-methoxycarbonylcinnaminate(3.2 g, 14.5 mmol) in anhydrous THF (40 ml) by syringe. After stirring at 40 °C for 4 h, the solvent was removed in vacuo. To the residue was added a solution of HCl (1 mol/L, 35 ml), and this solution was extracted with CH₂Cl₂ (3 × 40 ml). The combined organic phase was washed with saturated NaCl solution (2 × 30 ml), dried with Na₂SO₄, and concentrated. The crude product was separated by silica-gel columnchromatography (petroleum ether/EtOAc, 3:1) to afford colourless crystal of compound (I).