3-[(R)-3,3-Dichloro-2-hydroxy­prop­yl]-8-hydr­oxy-6-meth­oxy-1H-isochromen-1-one

Hua-Rong Huang; Yan-Xiong Fang; Zhi-Yun Du; Kun Zhang; Yong-Cheng Lin

doi:10.1107/S1600536808026391

. 2008 Aug 20;64(Pt 9):o1801. doi: 10.1107/S1600536808026391

3-[(R)-3,3-Dichloro-2-hydroxypropyl]-8-hydroxy-6-methoxy-1H-isochromen-1-one

Hua-Rong Huang ^a,^*, Yan-Xiong Fang ^a, Zhi-Yun Du ^a, Kun Zhang ^a, Yong-Cheng Lin ^b

PMCID: PMC2960720 PMID: 21201780

Abstract

The title compound, C₁₃H₁₂Cl₂O₅, is an isocoumarin compound which has been isolated from the ethyl acetate extract of the fermentation broth of actinomycete Streptomyces sp. (V₄) from the South China Sea. There are intra- and intermolecular hydrogen bonds and halogen bonds [Cl⋯Cl = 3.434 (2) Å; C—Cl⋯Cl = 121.6°]. The intermolecular O—H⋯O hydrogen bonds link molecules into chains along the b axis.

Related literature

For related literature, see: Larsen & Breinholt (1999 ▶).

Experimental

Crystal data

C₁₃H₁₂Cl₂O₅
M _r = 319.13
Monoclinic,
a = 9.483 (3) Å
b = 6.757 (2) Å
c = 10.548 (3) Å
β = 99.217 (5)°
V = 667.1 (4) Å³
Z = 2
Mo Kα radiation
μ = 0.50 mm⁻¹
T = 293 (2) K
0.50 × 0.34 × 0.21 mm

Data collection

Bruker SMART 1K area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.787, T _max = 0.902
4190 measured reflections
2524 independent reflections
2320 reflections with I > 2σ(I)
R _int = 0.019

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.095
S = 1.07
2524 reflections
184 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.39 e Å⁻³
Absolute structure: Flack (1983 ▶), 931 Friedel pairs
Flack parameter: 0.06 (8)

Data collection: SMART (Bruker, 1999 ▶); cell refinement: SAINT-Plus (Bruker, 1999 ▶); data reduction: SAINT-Plus; 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/S1600536808026391/ww2128sup1.cif

e-64-o1801-sup1.cif^{(18.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808026391/ww2128Isup2.hkl

e-64-o1801-Isup2.hkl^{(124KB, 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
O5—H5⋯O3ⁱ	0.82	2.18	2.913 (3)	149
O3—H3⋯O2	0.82	1.91	2.624 (2)	145

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work is supported by Guangdong Provincial Science Foundation.

supplementary crystallographic information

Comment

As a kind of natural products from marine microorganisms, 3-((R)-3,3-dichloro-2-hydroxypropyl)-8-hydroxy-6-methoxy-1H- isochromen-1-one, is a isocoumarin-related dihydrodiaportin compound, from the fermentation broth of actinomycetes Streptomyces sp. (V4). In the primary biotest, the title compound showed weak activity inhibiting AchE in vitro (IC₅₀ = 3.9 uM/ml).

Larsen et al. also reported dichlorodiaportin (Larsen & Breinholt, 1999), but it was isolated from quite different microorganism, the typical cheese-associated isolates of Penicillium nalgiovense, and its structure was only elucidated based on spectral analysis, and the absolute configuration was depicted S by comparison with the optical rotation of those reported for several analogues of known absolute configuration. However, according to the optical rotation and our crystal structure, it is clear that Larsen's compound is the same compound as our dichlorodiaportin.

We report here the crystal structure of (I). Compound (I) crystallizes in space group P 2₁, and the 8-hydroxy-isochromen-1-one core rings in (I) is a planar conjugated ring system (Fig.1). In the crystal structure, there is an intra- molecular hydrogen bond [O···O = 2.624 (2) Å, and O—H···O = 144.6°] of O—H···O type between O3 and O5 hyroxyl groups in (I), and adjacent molecules form an infinite one-dimensional chain along b axis via O—H···O intermolecular hydrogen bonds [O···O = 2.913 (3)Å, and O—H···O = 149.0°] between the O3 and O5 hydroxyl groups (Fig.1 and Table 2).

Experimental

A strain of streptomyces sp. (V₄) was isolated from the South China Sea, has been deposited in the School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, P. R. China.

Culture conditions: soluble starch 10 g l^-1, Ca carbonate 2 g l^-1, ammorium sulfate 2 g l^-1, dipotassium hydrogen phosphate 1 g l^-1, magnesium sulfate hydrated 1 g l^-1, sodium chloride 1 g l^-1, yeast extract 10 g l^-1, pH 7.2 and incubation at 298 K for 6 d. For the extraction and separation of the metabolite, the cultures (100 L) of (I) were filtered through cheesecloth. The filtrate was concentrated to 5L below 323 K, then extracted three times by shaking with an equal volume of ethyl acetate. The extract was evaporated under reduced pressure. The combined organic extracts were subjected to silica-gel column chromatography, eluting with petroleum ether/ethyl (1:1 v/v) acetate, to yield (I).

Colorless block crystals of (I) were obtained by evaporation of a methanol solution.

The compound identity was confirmed by NMR spectroscopy, Elemental Analysis, IR, FAB-MS, melting point and optical rotation.

¹H-NMR in CDCl₃ (500 MHz): 6.59 (s, 1H), 6,57 (d, J = 2.0 1H), 3.01 (m, 1H), 2.95 (m, 1H), 4.42 (m, 1H), 6.20 (d, J = 3.0 1H), 3.92 (s, 3H), 11.10 (s, OH) and 5.20 (d, J = 6.0, OH).

¹³C-NMR in CDCl₃ (125 MHz): 166.8 (C), 154 (C), 107.4 (CH), 140.4 (C), 102.1 (CH), 168.0 (C), 101.2 (CH), 164.3 (C), 111.4 (C), 37.3 (CH₂), 73.1 (CH), 77.2 (CH) and 56.3 (CH₃).

Elemental Analysis: C 48.91, H 3.97, calc. (for C₁₃H₁₂O₅C_l2): C 48.93, H 3.79%.

IR (KBr): 3474, 3032, 2986, 1693, 1643, 1568, 1465, 1356, 1237, 1197, 1096, 853, 790, 690.

FAB-MS: 319 [M]⁺, 321 [M+2]⁺, 235 [M-CHCl₂]⁺, 107, 77.

M.p. 419–420 K.

[α]²⁰_D = +7.8 (c = 0.05, MeOH).