PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2008 September 1; 64(Pt 9): o1801.
Published online 2008 August 20. doi:  10.1107/S1600536808026391
PMCID: PMC2960720

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

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 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-o1801-scheme1.jpg

Experimental

Crystal data

  • C13H12Cl2O5
  • M r = 319.13
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1801-efi1.jpg
  • 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 [triangle]) 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
  • Δρmax = 0.26 e Å−3
  • Δρmin = −0.39 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 931 Friedel pairs
  • Flack parameter: 0.06 (8)

Data collection: SMART (Bruker, 1999 [triangle]); cell refinement: SAINT-Plus (Bruker, 1999 [triangle]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808026391/ww2128sup1.cif

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

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

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 C13H12O5Cl2): 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]20D = +7.8 (c = 0.05, MeOH).

Refinement

The H atoms were positioned geometrically and were treated as riding on their parent C atoms, with C—H distances in the range of 0.93–0.98 Å, with Uiso (H) = 1.2–1.5 times Ueq of the parent atom. H atoms attached to O3 and O5 (hydroxyl oxygen atoms) were located in difference Fourier maps and refined initially with distance restraints of 0.82 Å with Uiso (H) = 1.5 times Ueq (O).

Figures

Fig. 1.
View of the molecules in the asymmetric unit of (I), with anisotropic displacement parameters drawn at the 50% probability level.
Fig. 2.
A view of the hydrogen-bonded molecular chains (Dashed lines). The chains are aligned parallel to the crystallographic b axis. H atoms not involved in H-bonding have been omitted for clarity. Symmetry codes: (I) 1 - x,y - 1/2,-z; (II) 1 - x,1/2 + y,-z. ...
Fig. 3.
Supplementary figure.

Crystal data

C13H12Cl2O5F000 = 328
Mr = 319.13Dx = 1.589 Mg m3
Monoclinic, P21Melting point: 420 K
Hall symbol: P 2ybMo Kα radiation λ = 0.71073 Å
a = 9.483 (3) ÅCell parameters from 1002 reflections
b = 6.757 (2) Åθ = 2.7–27.0º
c = 10.548 (3) ŵ = 0.50 mm1
β = 99.217 (5)ºT = 293 (2) K
V = 667.1 (4) Å3Block, colorless
Z = 20.50 × 0.34 × 0.21 mm

Data collection

Bruker SMART 1K area-detector diffractometer2524 independent reflections
Radiation source: fine-focus sealed tube2320 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.019
T = 293(2) Kθmax = 27.1º
[var phi] and ω scansθmin = 2.0º
Absorption correction: multi-scan(SADABS; Sheldrick, 1996)h = −12→11
Tmin = 0.787, Tmax = 0.902k = −8→7
4190 measured reflectionsl = −13→11

Refinement

Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.035  w = 1/[σ2(Fo2) + (0.0525P)2 + 0.1606P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.095(Δ/σ)max < 0.001
S = 1.07Δρmax = 0.26 e Å3
2524 reflectionsΔρmin = −0.39 e Å3
184 parametersExtinction correction: none
1 restraintAbsolute structure: Flack (1983), 931 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.06 (8)
Secondary atom site location: difference Fourier map

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
C10.54937 (19)0.4698 (4)−0.06308 (18)0.0334 (4)
C20.55042 (19)0.4661 (4)0.07326 (17)0.0317 (4)
C30.6821 (2)0.4688 (4)0.15853 (18)0.0356 (4)
C40.6830 (2)0.4614 (4)0.28857 (19)0.0387 (4)
H40.76940.46070.34460.046*
C50.5540 (2)0.4548 (4)0.33695 (18)0.0361 (4)
C60.4234 (2)0.4543 (4)0.25529 (18)0.0369 (4)
H60.33830.45010.28840.044*
C70.42213 (19)0.4602 (4)0.12326 (17)0.0332 (4)
C80.29092 (19)0.4610 (4)0.03216 (18)0.0358 (4)
H80.20380.45830.06190.043*
C90.29283 (18)0.4657 (4)−0.09298 (17)0.0332 (4)
C100.17165 (19)0.4676 (5)−0.20293 (17)0.0356 (4)
H10A0.17830.3505−0.25480.043*
H10B0.18210.5820−0.25620.043*
C110.02418 (19)0.4735 (5)−0.16418 (17)0.0393 (5)
H110.01610.3586−0.10910.047*
C12−0.0964 (2)0.4600 (5)−0.2789 (2)0.0471 (5)
H12−0.18760.4740−0.24730.057*
C130.4413 (3)0.4492 (5)0.5247 (2)0.0502 (5)
H13A0.38750.56770.50150.075*
H13B0.46730.44290.61630.075*
H13C0.38430.33590.49500.075*
Cl1−0.08373 (8)0.65243 (17)−0.39091 (7)0.0803 (3)
Cl2−0.09425 (9)0.22660 (16)−0.35406 (9)0.0829 (3)
O10.42041 (13)0.4685 (3)−0.14183 (12)0.0349 (3)
O20.65509 (15)0.4724 (3)−0.11589 (14)0.0452 (4)
O30.80850 (14)0.4768 (3)0.11445 (14)0.0459 (4)
H30.79390.49400.03650.069*
O40.56832 (17)0.4506 (3)0.46640 (14)0.0463 (4)
O50.00051 (18)0.6449 (3)−0.09336 (15)0.0524 (5)
H50.03230.7420−0.12590.079*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0317 (8)0.0335 (10)0.0355 (9)0.0005 (10)0.0067 (7)−0.0017 (10)
C20.0315 (8)0.0309 (9)0.0325 (9)0.0027 (10)0.0044 (7)0.0009 (9)
C30.0321 (9)0.0324 (10)0.0414 (10)0.0010 (11)0.0034 (7)−0.0001 (10)
C40.0363 (9)0.0401 (10)0.0367 (10)0.0003 (11)−0.0033 (7)−0.0017 (11)
C50.0442 (10)0.0323 (10)0.0305 (9)−0.0006 (11)0.0016 (7)−0.0008 (10)
C60.0364 (9)0.0434 (11)0.0316 (9)0.0011 (11)0.0072 (7)0.0010 (10)
C70.0323 (9)0.0363 (10)0.0309 (9)−0.0008 (11)0.0046 (7)−0.0008 (10)
C80.0287 (8)0.0461 (11)0.0330 (9)0.0007 (11)0.0067 (7)0.0016 (11)
C90.0297 (8)0.0352 (10)0.0354 (9)−0.0024 (10)0.0070 (7)−0.0031 (10)
C100.0330 (8)0.0470 (11)0.0271 (8)0.0013 (11)0.0058 (6)−0.0018 (10)
C110.0333 (9)0.0568 (13)0.0281 (9)−0.0076 (11)0.0060 (7)−0.0016 (11)
C120.0311 (9)0.0760 (16)0.0349 (10)−0.0087 (14)0.0074 (7)−0.0079 (13)
C130.0613 (13)0.0601 (15)0.0300 (10)0.0009 (15)0.0095 (9)0.0023 (11)
Cl10.0525 (4)0.1251 (9)0.0574 (4)−0.0046 (4)−0.0090 (3)0.0333 (5)
Cl20.0561 (4)0.1063 (7)0.0842 (5)−0.0205 (4)0.0046 (4)−0.0486 (5)
O10.0296 (6)0.0467 (8)0.0291 (6)0.0006 (8)0.0062 (5)−0.0002 (7)
O20.0332 (7)0.0632 (10)0.0413 (7)0.0014 (9)0.0126 (6)0.0000 (9)
O30.0313 (6)0.0623 (10)0.0434 (8)0.0011 (9)0.0038 (5)0.0036 (9)
O40.0511 (8)0.0562 (9)0.0298 (7)0.0021 (10)0.0011 (6)0.0012 (8)
O50.0412 (8)0.0737 (13)0.0441 (8)0.0008 (9)0.0120 (6)−0.0175 (9)

Geometric parameters (Å, °)

C1—O21.223 (2)C9—C101.496 (2)
C1—O11.364 (2)C10—C111.519 (2)
C1—C21.437 (3)C10—H10A0.9700
C2—C71.402 (2)C10—H10B0.9700
C2—C31.417 (2)C11—O51.415 (3)
C3—O31.354 (2)C11—C121.529 (3)
C3—C41.371 (3)C11—H110.9800
C4—C51.400 (3)C12—Cl21.766 (3)
C4—H40.9300C12—Cl11.774 (3)
C5—O41.351 (2)C12—H120.9800
C5—C61.390 (3)C13—O41.437 (3)
C6—C71.391 (3)C13—H13A0.9600
C6—H60.9300C13—H13B0.9600
C7—C81.445 (2)C13—H13C0.9600
C8—C91.323 (3)O3—H30.8200
C8—H80.9300O5—H50.8200
C9—O11.389 (2)
O2—C1—O1116.32 (17)C9—C10—H10A108.6
O2—C1—C2125.56 (17)C11—C10—H10A108.6
O1—C1—C2118.12 (16)C9—C10—H10B108.6
C7—C2—C3119.41 (16)C11—C10—H10B108.6
C7—C2—C1120.64 (16)H10A—C10—H10B107.6
C3—C2—C1119.94 (16)O5—C11—C10113.2 (2)
O3—C3—C4118.72 (17)O5—C11—C12107.8 (2)
O3—C3—C2121.39 (17)C10—C11—C12112.93 (15)
C4—C3—C2119.89 (17)O5—C11—H11107.6
C3—C4—C5119.98 (17)C10—C11—H11107.6
C3—C4—H4120.0C12—C11—H11107.6
C5—C4—H4120.0C11—C12—Cl2110.3 (2)
O4—C5—C6124.15 (19)C11—C12—Cl1111.17 (19)
O4—C5—C4114.65 (17)Cl2—C12—Cl1110.42 (12)
C6—C5—C4121.19 (17)C11—C12—H12108.3
C5—C6—C7118.97 (18)Cl2—C12—H12108.3
C5—C6—H6120.5Cl1—C12—H12108.3
C7—C6—H6120.5O4—C13—H13A109.5
C6—C7—C2120.54 (17)O4—C13—H13B109.5
C6—C7—C8122.30 (17)H13A—C13—H13B109.5
C2—C7—C8117.15 (16)O4—C13—H13C109.5
C9—C8—C7121.02 (17)H13A—C13—H13C109.5
C9—C8—H8119.5H13B—C13—H13C109.5
C7—C8—H8119.5C1—O1—C9121.57 (14)
C8—C9—O1121.48 (16)C3—O3—H3109.5
C8—C9—C10129.93 (17)C5—O4—C13118.50 (15)
O1—C9—C10108.59 (15)C11—O5—H5109.5
C9—C10—C11114.68 (15)
O2—C1—C2—C7−179.0 (3)C1—C2—C7—C8−0.9 (4)
O1—C1—C2—C70.4 (4)C6—C7—C8—C9−179.7 (3)
O2—C1—C2—C31.1 (4)C2—C7—C8—C90.5 (4)
O1—C1—C2—C3−179.5 (2)C7—C8—C9—O10.4 (4)
C7—C2—C3—O3−179.2 (2)C7—C8—C9—C10−179.9 (3)
C1—C2—C3—O30.7 (4)C8—C9—C10—C112.8 (5)
C7—C2—C3—C41.4 (4)O1—C9—C10—C11−177.6 (2)
C1—C2—C3—C4−178.7 (2)C9—C10—C11—O561.4 (3)
O3—C3—C4—C5179.4 (2)C9—C10—C11—C12−175.8 (3)
C2—C3—C4—C5−1.2 (4)O5—C11—C12—Cl2−168.62 (15)
C3—C4—C5—O4−179.1 (3)C10—C11—C12—Cl265.6 (3)
C3—C4—C5—C60.4 (4)O5—C11—C12—Cl168.5 (2)
O4—C5—C6—C7179.6 (2)C10—C11—C12—Cl1−57.3 (3)
C4—C5—C6—C70.1 (4)O2—C1—O1—C9−180.0 (2)
C5—C6—C7—C20.1 (4)C2—C1—O1—C90.6 (4)
C5—C6—C7—C8−179.7 (3)C8—C9—O1—C1−1.0 (4)
C3—C2—C7—C6−0.8 (4)C10—C9—O1—C1179.3 (2)
C1—C2—C7—C6179.3 (3)C6—C5—O4—C13−1.2 (4)
C3—C2—C7—C8179.0 (2)C4—C5—O4—C13178.3 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O5—H5···O3i0.822.182.913 (3)149
O3—H3···O20.821.912.624 (2)145

Symmetry codes: (i) −x+1, y+1/2, −z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: WW2128).

References

  • Bruker (1999). SMART and SAINT-Plus Bruker AXS Inc, Madison, Wisconsin, USA.
  • Flack, H. D. (1983). Acta Cryst. A39, 876–881.
  • Larsen, T. O. & Breinholt, J. (1999). J. Nat. Prod.62, 1182–1184. [PubMed]
  • Sheldrick, G. M. (1996). SADABS University of Göttingen, Germany.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography