Issue contents cross.png
Download PDF of article cross.png
Download CIF cross.png
3D view cross.png
Navigation cross.png
Highlighting cross.png
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation cross.png
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
Text
cross.png
share
Previous article cross.png
Previous article cross.png
Issue contents cross.png
Download PDF of article cross.png
Download CIF cross.png
3D view cross.png
Navigation cross.png
Highlighting cross.png
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation cross.png
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
Text
cross.png
share

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296
Volume 67| Part 3| March 2011| Pages o125-o128
doi:10.1107/S0108270111005816

(+)-Geodin from Aspergillus terreus

CROSSMARK_Color_square_no_text.svg
Mads H. Rønnest,a,b Morten T. Nielsen,b Blanka Leber,c Uffe H. Mortensen,b Alwin Krämer,c Mads H. Clausen,a Thomas O. Larsenb and Pernille Harrisa*

aDepartment of Chemistry, Technical University of Denmark, Kemitorvet, Building 201 and 206, DK-2800 Kgs. Lyngby, Denmark, bCenter for Microbial Biotechnology, Department of Systems Biology, Søltofts Plads, Building 221 and 223, DK-2800 Kgs. Lyngby, Denmark, and cClinical Cooperation Unit for Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 280 (TP4), 69120 Heidelberg, Germany
*Correspondence e-mail: ph@kemi.dtu.dk

(Received 25 January 2011; accepted 16 February 2011; online 23 February 2011)

The fungal metabolite (+)-geodin [systematic name: (2R)-methyl 5,7-dichloro-4-hy­droxy-6′-meth­oxy-6-methyl-3,4′-di­oxo­spiro­[benzofuran-2,1′-cyclo­hexa-2′,5′-diene]-2′-carboxyl­ate], C17H12Cl2O7, was isolated from Aspergillus terreus. The crystal structure contains two independent mol­ecules in the asymmetric unit. Mol­ecules denoted 1 inter­act through O—H⋯O hydrogen bonds creating chains of mol­ecules parallel to the crystallographic 21 screw axis. Mol­ecules denoted 2 inter­act through an O⋯Cl halogen bond, also creating chains of mol­ecules parallel to the crystallographic 21 screw axis. Mol­ecules 1 and 2 inter­act through another O⋯Cl halogen bond. The two mol­ecules are similar but mol­ecules 2 have a slightly more planar cyclohexadiene ring than mol­ecules 1. The absolute structure of (+)-geodin has been unequivocally assigned with the spiro centre having the R configuration in both mol­ecules. The structurally related (+)-griseofulvin has an S configuration at the spiro centre, a difference of potential biological and biosynthetic relevance.

Comment

(+)-Geodin, (I)[link], was originally isolated from Aspergillus terreus (Raistrick & Smith, 1936[Raistrick, H. & Smith, G. (1936). Biochem. J. 30, 1315-1322.]) and elucidation of its structure was initiated (Clutterbuck et al., 1937[Clutterbuck, P. W., Koerber, W. & Raistrick, H. (1937). Biochem. J. 31, 1089-1092.]; Calam et al., 1939[Calam, C. T., Clutterbuck, P. W., Oxford, A. E. & Raistrick, H. (1939). Biochem. J. 33, 579-588.], 1947[Calam, C. T., Clutterbuck, P. W., Oxford, A. E. & Raistrick, H. (1947). Biochem. J. 41, 458-462.]), eventually resulting in the correct relative structure (Barton & Scott, 1958[Barton, D. H. R. & Scott, A. I. (1958). J. Chem. Soc. pp. 1767-1772.]). A number of biological activities have been reported for (I)[link], including anti­viral (Takatsuki, Suzuki et al., 1969[Takatsuki, A., Suzuki, S., Ando, K., Tamura, G. & Arima, K. (1969). Agric. Biol. Chem. Tokyo, 33, 1119-1123.]; Takatsuki, Yamaguchi et al., 1969[Takatsuki, A., Yamaguchi, I., Tamura, G., Misato, T. & Arima, K. (1969). J. Antibiot. 22, 442-445.]), anti­microbial (Rinderknecht et al., 1947[Rinderknecht, H., Ward, J. L., Bergel, F. & Morrison, A. L. (1947). Biochem. J. 41, 463-469.]), enhancement of fibrinolytic activity (Shinohara et al., 2000[Shinohara, C., Chikanishi, T., Nakashima, S., Hashimoto, A., Hamanaka, A., Endo, A. & Hasumi, K. (2000). J. Antibiot. 53, 262-268.]) and stimulation of glucose uptake for rat adipocytes (Sato et al., 2005[Sato, S., Okusa, N., Ogawa, A., Ikenoue, T., Seki, T. & Tsuji, T. (2005). J. Antibiot. 58, 583-589.]). Furthermore, (I)[link] is a subunit of the compound Sch 202596, an antagonist of the galanin receptor subtype GALR1 (Chu et al., 1997[Chu, M., Mierzwa, R., Truumees, I., King, A., Sapidou, E., Barrabee, E., Terracciano, J., Patel, M. G., Gullo, V. P., Burrier, R., Das, P. R., Mittelman, S. & Puar, M. S. (1997). Tetrahedron Lett. 38, 6111-6114.]). In an effort to synthesize Sch 202596, the total synthesis of racemic geodin was completed (Katoh et al., 2002[Katoh, T., Ohmori, O., Iwasaki, K. & Inoue, M. (2002). Tetrahedron, 58, 1289-1299.]; Katoh & Ohmori, 2000[Katoh, T. & Ohmori, O. (2000). Tetrahedron Lett. 41, 465-469.]). Geodin, (I)[link], shares the same grisan backbone as (+)-griseofulvin, (II), consisting of ring systems A, B and C, as shown for (II) in the Scheme below (Grove et al., 1952[Grove, J. F., MacMillan, J., Mulholland, T. P. C. & Rogers, M. A. T. (1952). J. Chem. Soc. pp. 3977-3987.]). Additionally, both compounds (I)[link] and (II) are dextrorotatory and this general similarity prompted our inter­est in (I)[link] since (II) has anti­cancer properties (Ho et al., 2001[Ho, Y. S., Duh, J. S., Jeng, J. H., Wang, Y. J., Liang, Y. C., Lin, C. H., Tseng, C. J., Yu, C. F., Chen, R. J. & Lin, J. K. (2001). Int. J. Cancer, 91, 393-401.]; Panda et al., 2005[Panda, D., Rathinasamy, K., Santra, M. K. & Wilson, L. (2005). Proc. Natl Acad. Sci. USA, 102, 9878-9883.]). (I)[link] was isolated from A. terreus and tested in our cellular anti­cancer assay (Rebacz et al., 2007[Rebacz, B., Larsen, T. O., Clausen, M. H., Rønnest, M. H., Löffler, H., Ho, A. D. & Krämer, A. (2007). Cancer Res. 67, 6342-6350.]) but did not exhibit any activity (data not shown).

[Scheme 1]

(I)[link] crystallizes with two independent mol­ecules in the asymmetric unit (Fig. 1)[link]. Although the two mol­ecules are quite similar, there are small differences in their geometries. Cyclo­hexa­dienone ring C in (I)[link] is almost planar, with an r.m.s. deviation of the least-square planes of 0.045 and 0.016 Å for mol­ecules 1 and 2, respectively. The largest deviation from this plane is 0.070 (2)/0.024 (2) Å found for atoms C12/C22. The distances O15⋯O13/O25⋯O23 are 4.999 (3)/5.245 (4) Å, reflecting the fact that the C ring in (I)[link] for mol­ecule 2 is slightly more planar than that of mol­ecule 1. In comparison, cyclo­hexenone ring C in griseofulvin, (II) (Putta­raja et al., 1982[Puttaraja, Nirmala, K. A., Sakegowda, D. S. & Duax, W. L. (1982). J. Crystallogr. Spectrosc. Res. 12, 415-423.]), has a half-chair conformation, with atoms C2 and C6′ on the opposite sides of the plane. This means that the distance O5⋯O3 is only 4.06 Å, i.e. much shorter than the equivalents O15⋯O13 and O25⋯O23 in (I)[link]. The ester groups in the two mol­ecules in the asymmetric unit of (I)[link] are rotated 21.4 (5)/16.9 (4)° with respect to the planes of the respective cyclo­hexa­dienone rings so that atoms O17/O27 are located more or less above the centre of the respective five-membered ring with short inter­atomic O17⋯O11/O27⋯O21 distances of 2.916 (4)/2.954 (3) Å. The five-membered B rings in the two mol­ecules in (I)[link] are rotated 89.89 (9)/88.13 (10)° with respect to the C rings. They are almost planar, with an r.m.s. deviation of the five atoms of 0.028/0.034 Å for both mol­ecules. However, atoms O11(O21) and C13(C23) are below the plane and C12(C22) above the plane. In both mol­ecules, there is an intra­molecular hydrogen bond from atom O12/O22 to O13/O23 (see Table 2[link]).

The crystal packing down the a axis is shown in Figs. 2[link] and 3[link], with the view showing the different packing of mol­ecules 1 (Fig. 3[link]a) and 2 (Fig. 3[link]b) down the c axis. Mol­ecules 1 are hydrogen bonded with a hydrogen bond from atom O12 to atom O15 in a neighbouring mol­ecule (see Table 2,[link] and Figs. 2[link] and 3[link]a). This creates a chain of mol­ecules along the crystallographic 21 screw axis. A similar hydrogen bond is not found in molecules 2. They are tilted slightly and the distance between atoms O22 and O25(−x + 2, y + [{1\over 2}], −z + 2) is 4.521 (4) Å. There are, however, halogen bonds between atoms O23 and Cl21 from neighbouring mol­ecules (see Table 1,[link] and Figs. 2[link] and 3[link]b) creating chains of mol­ecules along the crystallographic 21 screw axis. Furthermore, mol­ecules of type 2 are oriented so that the AB ring system stacks with the C ring from the next mol­ecule in the helix. Mol­ecules 1 and 2 inter­act via halogen bonds between atoms O27 and Cl12 (see Table 1[link]).

To increase knowledge of the structure–activity relationship of these related compounds (Rønnest et al., 2009[Rønnest, M. H., Rebacz, B., Markworth, L., Terp, A. H., Larsen, T. O., Krämer, A. & Clausen, M. H. (2009). J. Med. Chem. 52, 3342-3347.]) the absolute structure of (I)[link] presented here was determined using anomalous signal from all reflections (Flack, 1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]). This showed an R configuration at the spiro centre of both crystallographically independent mol­ecules. In contrast, for (II) the absolute configuration was determined based on alcoholytic reactions (MacMillan, 1959[MacMillan, J. (1959). J. Chem. Soc. pp. 1823-1830.]) and later verified by Brown & Sim (1963[Brown, W. A. C. & Sim, G. A. (1963). J. Chem. Soc. pp. 1050-1059.]) by crystal structure determination of a brominated derivative using film data to be S at the spiro centre and R at atom C6′. This structural difference between (I)[link] and (II) could potentially contribute to the observed absence of anti­cancer activity (Rebacz et al., 2007[Rebacz, B., Larsen, T. O., Clausen, M. H., Rønnest, M. H., Löffler, H., Ho, A. D. & Krämer, A. (2007). Cancer Res. 67, 6342-6350.]) for (I)[link].

Based on enzymatic studies of the biosynthesis of geodin, (I)[link] (Fujii et al., 1983[Fujii, I., Iijima, H., Ebizuka, Y. & Sankawa, U. (1983). Chem. Pharm. Bull. 31, 337-340.]), the spiro­cyclization reaction joining the B and C rings is believed to be catalysed by an enzyme of the multicopper protein class. The same reaction in the griseofulvin, (II), biosynthesis, on the other hand, is presumed to be mediated by a cytochrome P450 enzyme. The latter assumption is founded on the identification of the griseofulvin, (II), biosynthesis gene cluster (Chooi et al., 2010[Chooi, Y. H., Cacho, R. & Tang, Y. (2010). Chem. Biol. 17, 483-494.]). These observations could explain the different configuration of the spiro centres of (I)[link] and (II) since it is reasonable that enzymes of different classes lead to a disparate outcome in a similar reaction with comparable substrates.

[Figure 1]
Figure 1
A perspective view of the two independent molecules of geodin, (I)[link], showing the atom-numbering scheme and with displacement ellipsoids drawn at the 50% probability level.
[Figure 2]
Figure 2
The mol­ecular packing of (I)[link], showing the hydrogen- and halogen-bond architecture; the view direction is down [100]. Hydrogen and halogen bonds are drawn as dashed lines. [Symmetry codes: (i) −x + 1, y + [{1\over 2}], −z + 2; (ii) −x, y − [{1\over 2}], −z + 1.]
[Figure 3]
Figure 3
Helical chains in (I)[link], viewed in the [001] direction, showing (a) mol­ecules of type 1 and (b) mol­ecules of type 2. [Symmetry codes: (i) −x + 1, y + [{1\over 2}], −z + 2; (ii) −x, y − [{1\over 2}], −z + 1.]

Experimental

A. terreus [IBT 28226, culture collection at Department of Systems Biology, Technical University of Denmark (Lyngby, Denmark)] was cultured on 50 plates of yeast extract sucrose agar at 298 K for 7 d, extracted with ethyl acetate (2 l) and then concentrated to afford 1.2 g of raw extract. The raw extract was dissolved in 10% H2O in MeOH (50 ml) and the aqueous phase was extracted with heptane (50 ml). The water content was increased to 50% by adding H2O (40 ml) and the resulting mixture was shaken with CH2Cl2 (90 ml). The CH2Cl2 phase was concentrated (0.86 g) and further purification was performed on a Phenomenex Luna(2) HPLC column (250 × 10 mm, 5 µm, C-18) using 5 ml min−1 H2O/CH3CN (isocratic run at 50/50 for 15 min) as the mobile phase to yield (I)[link] (11.6 mg as a yellow oil). Geodin, (I)[link], was crystallized using sitting-drop vapour diffusion, the drop consisting of EtOAc–heptane (4:1 v/v) and the reservoir containing heptane, to afford yellow crystals.

Crystal data

  • C17H12Cl2O7

  • Mr = 399.17

  • Monoclinic, P 21

  • a = 8.9276 (3) Å

  • b = 11.3625 (4) Å

  • c = 16.5006 (6) Å

  • β = 94.456 (1)°

  • V = 1668.76 (10) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.43 mm−1

  • T = 120 K

  • 0.25 × 0.15 × 0.08 mm
Data collection

  • Bruker SMART platform CCD diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2000[Bruker (2000). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.82, Tmax = 0.97

  • 22828 measured reflections

  • 8165 independent reflections

  • 7496 reflections with I > 2σ(I)

  • Rint = 0.029
Refinement

  • R[F2 > 2σ(F2)] = 0.053

  • wR(F2) = 0.145

  • S = 1.06

  • 8165 reflections

  • 480 parameters

  • 1 restraint

  • H-atom parameters constrained

  • Δρmax = 0.81 e Å−3

  • Δρmin = −0.36 e Å−3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 3819 Friedel pairs

  • Flack parameter: 0.04 (6)

Table 1
Selected interatomic distances (Å)

O27⋯Cl12 3.070 (3)
O23⋯Cl21i 3.006 (3)
Symmetry code: (i) [-x+1, y+{\script{1\over 2}}, -z+2].

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O12—H12⋯O15ii 0.84 2.33 2.916 (3) 128
O12—H12⋯O13 0.84 2.50 3.149 (3) 135
O22—H22⋯O23 0.84 2.36 3.021 (4) 136
Symmetry code: (ii) [-x, y-{\script{1\over 2}}, -z+1].

H atoms were observed in a difference synthesis and subsequently placed in idealized positions. They were refined using a riding model, with aryl C—H = 0.95 Å and Uiso(H) = 1.2Ueq(C), methyl C—H = 0.98 Å and Uiso(H) = 1.5Ueq(C), and hy­droxy O—H = 0.84 Å and Uiso(H) = 1.2Ueq(O).

Data collection: SMART and SAINT (Bruker, 1998[Bruker (1998). SMART and SAINT. Versions 5.054. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SMART and SAINT; data reduction: SMART and SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]) and Mercury (Macrae et al., 2006[Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453-457.]); software used to prepare material for publication: enCIFer (Allen et al., 2004[Allen, F. H., Johnson, O., Shields, G. P., Smith, B. R. & Towler, M. (2004). J. Appl. Cryst. 37, 335-338.]).

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S0108270111005816/lg3050sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S0108270111005816/lg3050Isup2.hkl


Comment top

(+)-Geodin, (I) , was originally isolated from Aspergillus terreus (Raistrick & Smith, 1936) and elucidation of its structure was initiated (Clutterbuck et al., 1937; Calam et al., 1939, 1947), eventually resulting in the correct relative structure (Barton & Scott, 1958). A number of biological activities have been reported for (I) including antiviral (Takatsuki, Suzuki et al., 1969; Takatsuki, Yamaguchi et al., 1969), antimicrobial (Rinderknecht et al., 1947), enhancement of fibrinolytic activity (Shinohara et al., 2000) and stimulation of glucose uptake for rat adipocytes (Sato et al., 2005). Furthermore, (I) is a subunit of the compound Sch 202596, an antagonist of the galanin receptor subtype GALR1 (Chu et al., 1997). In an effort to synthesize Sch 202596, the total synthesis of racemic geodin was completed (Katoh et al., 2002; Katoh & Ohmori, 2000). Geodin, (I), shares the same grisan backbone as (+)-griseofulvin, (II), consisting of ring systems A, B and C as shown for (II) in the scheme (Grove et al., 1952). Additionally, both compounds (I) and (II) are dextrorotatory and this general similarity prompted our interest in (I) since (II) has anticancer properties (Ho et al., 2001; Panda et al., 2005). (I) was isolated from A. terreus and tested in our cellular anticancer assay (Rebacz et al., 2007) but did not exhibit any activity (data not shown).

(+)-Geodin, (I), crystallizes with two independent molecules in the asymmetric unit shown in Fig. 1. Although the two molecules are quite similar, there are small differences in their geometries. The cyclohexadienone C ring in (I) is almost planar, with an r.m.s. deviation of the least-square planes of 0.045 and 0.016 Å for molecules 1 and 2, respectively. The largest deviation from this plane is 0.070 (2)/0.024 (2) Å found for C12/C22. The distances O15—O13/O25—O23 are 4.999 (3)/5.245 (4) Å, reflecting the fact that the C ring in (I) for molecule 2 is slightly more planar than the C ring in (I) for molecule 1. In comparison, the cyclohexenone C ring in griseofulvin, (II) (Puttaraja et al., 1982), has a half-chair conformation, with C2 and C6' on the opposite sides of the plane. This means that the distance O5—O3 is only 4.06 Å, i. e. much shorter than the equivalents O15—O13 and O25—O23 in (I). The ester groups in the two molecules in the asymmetric unit of (I) are rotated 21.4 (5)/16.9 (4)° with respect to the respective cyclohexadienone rings so that O17/O27 are located more or less above the centre of the respective five-membered ring with short interatomic distances between O17—O11/O27—O21 of 2.916 (4)/2.954 (3) Å. The five-membered B rings in the two molecules in (I) are rotated 89.89 (9)/88.13 (10)° with respect to the C rings. They are almost planar, with an r.m.s. deviation of the five atoms of 0.028/0.034 Å for both molecules. However, O11(O21) and C13(C23) are below the plane and C12(C22) above the plane. In both molecules there is an intramolecular hydrogen bond from O12/O22 to O13/O23 (see Table 2).

The crystal packing down the a axis is shown in Figs. 2 and 3, with the view showing different packing of molecules 1 (Fig. 3a) and 2 (Fig. 3b) down the c axis. Molecules 1 are hydrogen bonded with a hydrogen bond from O12 to O15 in a neighbouring molecule (see Table 2 and Figs. 2, 3a). This creates a helical chain of molecules along the b axis. Molecules 2 are not interacting through a similar hydrogen bond. They are tilted slightly and the distance between O22 and O25 (symmetry code: 2 - x,1/2 + y, 2 - z) is 4.521 (4) Å. There are, however, halogen bonds between O23 and Cl21 from neighbouring molecules (see Table 1 and Figs. 2 and 3b) creating helical chains of molecules along the b axis. Furthermore, molecules of type 2 are oriented so that the AB ring system stacks with the C ring from the next molecule in the helix. Molecules 1 and 2 interact via halogen bonds between O27 and Cl12 (see Table 1).

To increase knowledge of the structure–activity relationship of these related compounds (Rønnest et al., 2009), the absolute structure of (I) presented here was determined using anomalous signal from all reflections (Flack, 1983) showing an R configuration at the spiro centre of both crystallographically independent molecules. In contrast, for (II) the absolute configuration was determined, based on alcoholytic reactions (MacMillan, 1959) and later verified by Brown & Sim (1963) by crystal structure determination of a brominated derivative using film data, to be S on the spiro centre and R on the C6' atom. This structural difference between (I) and (II) could potentially contribute to the observed absence of anticancer activity (Rebacz et al., 2007) for (I).

Based on enzymatic studies of the biosynthesis of geodin, (I) (Fujii et al., 1983), the spirocyclization reaction joining the B and C rings is believed to be catalysed by an enzyme of the multi-copper protein class. The same reaction in the griseofulvin, (II), biosynthesis, on the other hand, is presumed to be mediated by a cytochrome P450 enzyme. The latter assumption is founded on the identification of the griseofulvin, (II), biosynthesis gene cluster (Chooi et al., 2010). These observations could explain the different orientation of the spiro centres of (I) and (II), since it is reasonable that enzymes of different classes lead to a disparate outcome in a similar reaction with comparable substrates.

Related literature top

For related literature, see: Puttaraja Nirmala Sakegowda Duax (1982); Barton & Scott (1958); Brown & Sim (1963); Calam et al. (1939, 1947); Chooi et al. (2010); Chu et al. (1997); Clutterbuck et al. (1937); Flack (1983); Fujii et al. (1983); Grove et al. (1952); Ho et al. (2001); Katoh & Ohmori (2000); Katoh et al. (2002); Panda et al. (2005); Rønnest et al. (2009); Raistrick & Smith (1936); Rebacz et al. (2007); Rinderknecht et al. (1947); Sato et al. (2005); Shinohara et al. (2000).

Experimental top

A. terreus [IBT 28226, culture collection at Department of Systems Biology, Technical University of Denmark (Lyngby, Denmark)] was cultured on 50 plates of yeast extract sucrose agar at 298 K for 7 d and extracted with ethyl acetate (2 l) then concentrated to afford 1.2 g raw extract. The raw extract was dissolved in 10% H2O in MeOH (50 ml) and the aqueous phase was extracted with heptane (50 ml). The water content was increased to 50% by adding 40 ml H2O and shaken with CH2Cl2 (90 ml). The CH2Cl2 phase was concentrated (0.86 g) and further purification was performed on a Phenomenex, Luna(2) HPLC column (250 × 10 mm, 5 µm, C-18) using 5 ml min-1 H2O/CH3CN (isocratic run at 50/50 for 15 min) as the mobile phase to yield (I) (11.6 mg as a yellow oil). Geodin, (I), was crystallized using sitting drop vapour diffusion, the drop consisting of EtOAc:heptane 4:1 and the reservoir containing heptane, to afford yellow crystals.

Refinement top

H atoms were observed in a difference synthesis and located in idealized positions. They were refined using a riding model with aryl C—H = 0.95 Å and Uiso(H) = 1.2Ueq(C), methyl C—H = 0.98 Å and Uiso(H) = 1.5Ueq(C), and hydroxy O—H = 0.84 Å and Uiso(H) = 1.2Ueq(O).

Computing details top

Data collection: SMART and SAINT (Bruker, 1998); cell refinement: SMART and SAINT (Bruker, 1998); data reduction: SMART and SAINT (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2006); software used to prepare material for publication: enCIFer (Allen et al., 2004).

Figures top
[Figure 1] Fig. 1. A perspective view of geodin, (I), showing the atom-numbering scheme and with displacement ellipsoids drawn at the 50% probability level.
[Figure 2] Fig. 2. The molecular packing of (I), showing the hydrogen- and halogen-bond architecture; the view direction is down [100]. Hydrogen and halogen bonds are drawn as dashed lines. [Symmetry codes: (i) -x + 1, y + 1/2, -z + 2; (ii) -x, y - 1/2, -z + 1.]
[Figure 3] Fig. 3. Helical chains in (I), viewed in the [001] direction, showing (a) molecules of type 1 and (b) molecules of type 2. [Symmetry codes: (i) -x + 1, y + 1/2, -z + 2; (ii) -x, y - 1/2, -z + 1.]
(2R)-methyl 5,7-dichloro-4-hydroxy-6'-methoxy-6-methyl-3,4'-dioxospiro[benzofuran-2,1'- cyclohexa-2',5'-diene]-2'-carboxylate top
Crystal data top
C17H12Cl2O7F(000) = 816
Mr = 399.17Dx = 1.589 Mg m−3
Monoclinic, P21Melting point = 503–505 K
Hall symbol: P 2ybMo Kα radiation, λ = 0.71073 Å
a = 8.9276 (3) ÅCell parameters from 7659 reflections
b = 11.3625 (4) Åθ = 2.2–28.1°
c = 16.5006 (6) ŵ = 0.43 mm−1
β = 94.456 (1)°T = 120 K
V = 1668.76 (10) Å3Block, colourless
Z = 40.25 × 0.15 × 0.08 mm
Data collection top
Bruker SMART platform CCD
diffractometer		8165 independent reflections
Radiation source: fine-focus sealed tube7496 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.029
ω scansθmax = 28.3°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Bruker, 2000)		h = −11→11
Tmin = 0.82, Tmax = 0.97k = −15→15
22828 measured reflectionsl = −22→21
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.053H-atom parameters constrained
wR(F2) = 0.145 w = 1/[σ2(Fo2) + (0.0894P)2 + 0.6625P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
8165 reflectionsΔρmax = 0.81 e Å−3
480 parametersΔρmin = −0.36 e Å−3
1 restraintAbsolute structure: Flack (1983), ???? Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.04 (6)
Crystal data top
C17H12Cl2O7V = 1668.76 (10) Å3
Mr = 399.17Z = 4
Monoclinic, P21Mo Kα radiation
a = 8.9276 (3) ŵ = 0.43 mm−1
b = 11.3625 (4) ÅT = 120 K
c = 16.5006 (6) Å0.25 × 0.15 × 0.08 mm
β = 94.456 (1)°
Data collection top
Bruker SMART platform CCD
diffractometer		8165 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2000)		7496 reflections with I > 2σ(I)
Tmin = 0.82, Tmax = 0.97Rint = 0.029
22828 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.053H-atom parameters constrained
wR(F2) = 0.145Δρmax = 0.81 e Å−3
S = 1.06Δρmin = −0.36 e Å−3
8165 reflectionsAbsolute structure: Flack (1983), ???? Friedel pairs
480 parametersAbsolute structure parameter: 0.04 (6)
1 restraint
Special details top

Experimental. 1H NMR spectra were recorded using either a Varian Unity Inova 500 MHz or a Bruker Avance 800 MHz spectrometer. 13C NMR data were recorded using a Bruker Avance 800 MHz spectrometer. Chemical shifts were measured in ppm and coupling constants in Hz. When benzene-d6 was used as solvent the residual peak was used as internal reference at 7.15 for 1H NMR and δ 128.0 for 13C NMR spectra. For DMSO-d6 the value was δ 2.50 for 1H NMR. The IR spectrum was recorded using a Bruker Alpha ATR and measured in cm-1. The melting point is uncorrected.

High-resolution LC-DAD-MS was performed on an Agilent 1100 system equipped with a photodiode array detector (DAD) and coupled to a LCT orthogonal time-of-flight mass spectrometer (Waters-Micromass, Manchester, UK) with a Z-spray electrospray ionisation (ESI) source and a LockSpray probe (M+H 556.2771) and controlled by MassLynx 4.0 software. LC-MS calibration from m/z 100-900 was done with a PEG mixture. Standard separation involved a LUNA 2 column with an acetonitrile (50 ppm formic acid) in water gradient starting from 15% to 100% over 25 minutes with a flow rate of 0.3 mL/min. Purity was assessed by UPLC-DAD on a Dionex ultimate 3000 system. The column used was a Kinetex (150 × 2.10 mm, 2.6 µm, C-18) at 357K with a flow of 0.8 mL.

(R)-Methyl 5,7-dichloro-4-hydroxy-6'-methoxy-6-methyl-3,4'-dioxo-spiro[benzofuran-2,1' -cyclohexa-2',5'-diene]-2'-carboxylate (I) (geodin). m.p.: 503-505 K. (in agreement with litt. (Raistrick & Smith, 1936)). IR(neat): 3396, 1724, 1659, 1610, 1461, 1440; 1H NMR (800 MHz, benzene-d6): δ 7.04 (1H, d, J = 1.0 Hz), 5.43 (1H, d, J = 1.0 Hz), 2.91 (3H, s), 2.53 (3H, s), 2.00 (3H, s); 13C NMR (200 MHz, benzene-d6): δ 194.3, 184.8, 167.8, 166.4, 163.9, 150.4, 147.1, 137.9, 137.7, 115.5, 110.0, 110.0, 105.1, 85.4, 56.3, 52.5, 18.5; 1H NMR (800 MHz, CDCl3): δ 7.14 (1H, d, J = 1.5 Hz), 5.82 (1H, d, J = 1.5 Hz), 3.74 (3H, s), 3.70 (3H, s), 2.58 (3H, s) (in agreement with litt. (Sato et al., 2005)); 1H NMR (500 MHz, DMSO-d6): δ 7.05 (1H, d, J = 1.0 Hz), 6.05 (1H, d, J = 1.0 Hz), 3.72 (3H, s), 3.68 (3H, s), 2.52 (3H, s); HRMS (ESI+) calcd for [M + H]+ [C17H13Cl2O7]+ 399.0038, found 399.0041. [α]D21+129° (c = 1.16, CHCl3) (in agreement with litt. (Raistrick & Smith, 1936)).

1H NMR (800 MHz, benzene-d6), 13C NMR (200 MHz, benzene-d6) and UPLC-DAD chromatogram and UV spectrum may be provided.

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) top
xyzUiso*/Ueq
Cl110.77294 (8)1.10305 (7)0.51669 (5)0.02928 (18)
Cl120.68174 (9)0.76827 (7)0.74489 (5)0.02806 (17)
C120.2904 (3)1.0248 (3)0.46073 (17)0.0179 (5)
C130.2710 (3)0.9240 (3)0.52477 (17)0.0176 (5)
C140.4678 (3)0.8393 (3)0.63238 (17)0.0191 (6)
C150.6180 (3)0.8536 (3)0.66243 (18)0.0217 (6)
C160.7146 (3)0.9350 (3)0.62866 (19)0.0208 (6)
C170.6610 (3)1.0031 (3)0.56252 (18)0.0205 (6)
C180.5125 (3)0.9899 (3)0.53254 (17)0.0185 (5)
C190.4176 (3)0.9111 (3)0.56750 (18)0.0195 (6)
C1100.1999 (4)1.2757 (3)0.5897 (2)0.0352 (8)
H10A0.20501.34020.55050.053*
H10B0.25671.29710.64070.053*
H10C0.09481.26100.59980.053*
C1110.3348 (4)0.8830 (3)0.3471 (2)0.0264 (6)
C1120.3791 (4)0.7635 (4)0.2364 (2)0.0356 (8)
H12A0.48800.76430.24980.053*
H12B0.35830.75850.17730.053*
H12C0.33510.69540.26210.053*
C1130.8741 (3)0.9498 (3)0.6638 (2)0.0284 (7)
H13A0.94160.95000.61970.043*
H13B0.90080.88450.70090.043*
H13C0.88381.02440.69350.043*
C12'0.2441 (3)0.9830 (3)0.37629 (18)0.0204 (5)
C13'0.1215 (3)1.0253 (3)0.33437 (18)0.0248 (6)
H13'0.09210.99290.28250.030*
C14'0.0305 (3)1.1208 (3)0.36604 (19)0.0246 (6)
C15'0.0845 (3)1.1747 (3)0.44209 (18)0.0220 (6)
H15'0.03401.24140.46150.026*
C16'0.2052 (3)1.1315 (3)0.48547 (17)0.0179 (5)
O110.4490 (2)1.05172 (19)0.46832 (12)0.0181 (4)
O120.3804 (2)0.7615 (2)0.66797 (13)0.0234 (4)
H120.29950.75260.63910.028*
O130.1531 (2)0.8759 (2)0.53523 (14)0.0227 (4)
O15−0.0860 (3)1.1517 (3)0.32749 (15)0.0359 (6)
O160.3138 (3)0.8709 (2)0.26598 (14)0.0304 (5)
O170.4118 (3)0.8220 (3)0.39071 (16)0.0381 (6)
O180.2635 (3)1.1708 (2)0.55715 (14)0.0264 (5)
Cl210.21268 (10)0.68838 (9)0.98643 (6)0.0381 (2)
Cl220.29043 (14)1.02171 (10)0.75500 (5)0.0497 (3)
C220.6856 (4)0.8043 (3)1.0535 (2)0.0261 (7)
C230.7022 (4)0.8869 (3)0.97828 (19)0.0264 (7)
C240.5033 (4)0.9567 (3)0.8691 (2)0.0314 (7)
C250.3560 (5)0.9402 (3)0.8397 (2)0.0336 (8)
C260.2601 (4)0.8595 (4)0.8745 (2)0.0325 (8)
C270.3179 (4)0.7952 (3)0.9430 (2)0.0271 (7)
C280.4637 (4)0.8154 (3)0.97430 (19)0.0244 (6)
C290.5549 (4)0.8932 (3)0.93790 (19)0.0261 (7)
C2100.5980 (4)1.0485 (3)1.1921 (2)0.0349 (8)
H10D0.59291.00651.24370.052*
H10E0.51241.10231.18410.052*
H10F0.69181.09351.19330.052*
C2110.7857 (4)0.6341 (3)0.9804 (2)0.0276 (7)
C2120.8641 (5)0.4635 (4)0.9149 (2)0.0443 (10)
H12D0.76130.44300.89460.066*
H12E0.92210.39140.92630.066*
H12F0.91130.50990.87380.066*
C2130.0996 (5)0.8412 (4)0.8394 (2)0.0436 (10)
H13D0.05400.91760.82500.065*
H13E0.04180.80230.87980.065*
H13F0.09940.79190.79070.065*
C22'0.7923 (4)0.7050 (3)1.0540 (2)0.0264 (6)
C23'0.8995 (4)0.6864 (3)1.11702 (19)0.0254 (6)
H23'0.96680.62201.11480.030*
C24'0.9111 (4)0.7650 (3)1.1877 (2)0.0296 (7)
C25'0.8064 (4)0.8621 (3)1.1905 (2)0.0282 (7)
H25'0.81450.91401.23580.034*
C26'0.6970 (4)0.8808 (3)1.1301 (2)0.0267 (6)
O210.5323 (2)0.7591 (2)1.04053 (13)0.0259 (5)
O220.5966 (3)1.0313 (2)0.83171 (16)0.0391 (6)
H220.68641.01470.84620.047*
O230.8176 (3)0.9357 (2)0.96332 (16)0.0339 (6)
O251.0111 (3)0.7473 (3)1.24223 (15)0.0380 (6)
O260.8604 (3)0.5322 (2)0.98897 (15)0.0344 (6)
O270.7207 (3)0.6632 (3)0.91666 (15)0.0363 (6)
O280.5933 (3)0.9637 (2)1.12531 (15)0.0317 (5)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl110.0183 (3)0.0322 (4)0.0374 (4)−0.0052 (3)0.0023 (3)0.0098 (3)
Cl120.0270 (4)0.0315 (4)0.0249 (4)0.0039 (3)−0.0028 (3)0.0089 (3)
C120.0139 (12)0.0215 (14)0.0182 (12)−0.0012 (10)0.0008 (9)0.0013 (11)
C130.0160 (13)0.0180 (13)0.0188 (13)0.0010 (10)0.0024 (10)−0.0011 (10)
C140.0193 (13)0.0203 (14)0.0181 (13)0.0008 (11)0.0036 (10)−0.0003 (11)
C150.0206 (14)0.0260 (15)0.0183 (13)0.0057 (11)0.0004 (11)0.0014 (11)
C160.0150 (12)0.0243 (14)0.0227 (14)−0.0001 (11)−0.0003 (10)0.0003 (11)
C170.0159 (13)0.0213 (14)0.0246 (14)−0.0004 (10)0.0021 (10)−0.0026 (11)
C180.0148 (12)0.0222 (14)0.0186 (13)0.0006 (11)0.0020 (10)−0.0010 (11)
C190.0164 (13)0.0223 (14)0.0202 (13)0.0010 (11)0.0032 (10)0.0000 (11)
C1100.045 (2)0.0272 (17)0.0341 (17)0.0091 (16)0.0053 (15)−0.0095 (15)
C1110.0285 (15)0.0232 (15)0.0284 (16)−0.0056 (12)0.0088 (12)−0.0056 (12)
C1120.045 (2)0.0326 (18)0.0300 (16)0.0024 (16)0.0106 (14)−0.0131 (14)
C1130.0168 (14)0.0338 (18)0.0336 (17)−0.0021 (12)−0.0032 (12)0.0037 (14)
C12'0.0225 (13)0.0191 (13)0.0200 (13)−0.0049 (11)0.0043 (10)−0.0020 (10)
C13'0.0232 (14)0.0320 (16)0.0188 (13)−0.0026 (12)−0.0001 (11)0.0003 (12)
C14'0.0194 (13)0.0282 (16)0.0261 (15)0.0009 (12)0.0016 (11)0.0064 (12)
C15'0.0184 (13)0.0206 (14)0.0276 (14)0.0038 (11)0.0054 (11)0.0021 (11)
C16'0.0146 (12)0.0191 (13)0.0203 (13)−0.0001 (10)0.0033 (10)0.0004 (10)
O110.0127 (9)0.0230 (10)0.0189 (9)−0.0006 (8)0.0026 (7)0.0057 (8)
O120.0215 (10)0.0260 (11)0.0224 (10)−0.0040 (9)−0.0001 (8)0.0055 (9)
O130.0168 (9)0.0213 (10)0.0306 (11)−0.0033 (8)0.0043 (8)0.0001 (9)
O150.0256 (12)0.0488 (15)0.0322 (13)0.0091 (11)−0.0048 (10)0.0041 (11)
O160.0383 (13)0.0306 (12)0.0227 (11)0.0045 (10)0.0049 (9)−0.0066 (9)
O170.0437 (15)0.0376 (14)0.0326 (13)0.0189 (12)0.0005 (11)−0.0057 (11)
O180.0285 (11)0.0243 (11)0.0261 (11)0.0035 (9)0.0016 (9)−0.0064 (9)
Cl210.0256 (4)0.0407 (5)0.0470 (5)−0.0043 (3)−0.0025 (3)−0.0020 (4)
Cl220.0749 (7)0.0501 (6)0.0225 (4)0.0376 (5)−0.0056 (4)0.0027 (4)
C220.0216 (14)0.0313 (17)0.0251 (15)−0.0013 (12)−0.0007 (11)0.0076 (12)
C230.0308 (16)0.0264 (16)0.0225 (14)0.0028 (13)0.0052 (12)0.0063 (12)
C240.047 (2)0.0252 (16)0.0229 (15)0.0152 (15)0.0066 (14)0.0068 (13)
C250.048 (2)0.0331 (18)0.0191 (15)0.0230 (16)−0.0021 (14)0.0012 (13)
C260.0330 (17)0.0387 (19)0.0245 (15)0.0197 (15)−0.0060 (13)−0.0102 (14)
C270.0274 (16)0.0280 (17)0.0256 (15)0.0088 (12)−0.0002 (12)−0.0019 (12)
C280.0260 (15)0.0271 (16)0.0202 (14)0.0072 (12)0.0022 (11)0.0038 (12)
C290.0302 (16)0.0266 (16)0.0216 (14)0.0075 (12)0.0036 (12)0.0046 (12)
C2100.0380 (19)0.0325 (18)0.0342 (18)0.0047 (15)0.0034 (14)−0.0090 (14)
C2110.0247 (15)0.0249 (16)0.0337 (17)0.0014 (12)0.0048 (13)0.0105 (13)
C2120.060 (3)0.038 (2)0.0341 (19)0.0152 (19)0.0048 (18)−0.0075 (16)
C2130.044 (2)0.049 (2)0.036 (2)0.0201 (19)−0.0140 (17)−0.0143 (17)
C22'0.0235 (14)0.0283 (16)0.0274 (16)−0.0010 (12)0.0020 (12)0.0065 (12)
C23'0.0274 (15)0.0248 (15)0.0241 (14)−0.0044 (12)0.0033 (12)0.0077 (12)
C24'0.0286 (16)0.0313 (16)0.0292 (16)−0.0047 (14)0.0044 (13)0.0078 (14)
C25'0.0291 (16)0.0289 (16)0.0267 (15)−0.0051 (13)0.0023 (12)−0.0021 (13)
C26'0.0301 (16)0.0248 (16)0.0251 (15)−0.0055 (13)0.0013 (12)0.0030 (12)
O210.0194 (10)0.0333 (12)0.0243 (10)0.0013 (9)−0.0019 (8)0.0087 (10)
O220.0564 (17)0.0286 (13)0.0331 (13)0.0075 (12)0.0082 (12)0.0172 (11)
O230.0353 (13)0.0286 (13)0.0387 (14)−0.0032 (10)0.0095 (11)0.0057 (11)
O250.0311 (13)0.0461 (16)0.0348 (13)−0.0030 (11)−0.0101 (10)0.0010 (11)
O260.0418 (14)0.0313 (13)0.0305 (12)0.0133 (11)0.0056 (10)0.0008 (10)
O270.0462 (15)0.0391 (14)0.0224 (11)0.0092 (12)−0.0057 (10)−0.0075 (10)
O280.0355 (13)0.0309 (13)0.0291 (12)0.0039 (10)0.0054 (10)−0.0052 (10)
Geometric parameters (Å, º) top
Cl11—C171.726 (3)Cl21—C271.724 (4)
Cl12—C151.731 (3)Cl22—C251.740 (3)
C12—O111.444 (3)C22—O211.462 (4)
C12—C12'1.500 (4)C22—C22'1.477 (5)
C12—C16'1.504 (4)C22—C26'1.530 (5)
C12—C131.577 (4)C22—C231.572 (4)
C13—O131.210 (4)C23—O231.212 (4)
C13—C191.445 (4)C23—C291.429 (5)
C14—O121.344 (4)C24—O221.368 (5)
C14—C191.392 (4)C24—C251.378 (6)
C14—C151.403 (4)C24—C291.393 (4)
C15—C161.408 (4)C25—C261.407 (6)
C16—C171.392 (4)C26—C271.409 (5)
C16—C1131.505 (4)C26—C2131.517 (5)
C17—C181.387 (4)C27—C281.382 (5)
C18—O111.358 (3)C28—O211.369 (4)
C18—C191.389 (4)C28—C291.372 (5)
C110—O181.441 (4)C210—O281.461 (4)
C110—H10A0.9800C210—H10D0.9800
C110—H10B0.9800C210—H10E0.9800
C110—H10C0.9800C210—H10F0.9800
C111—O171.180 (4)C211—O271.207 (4)
C111—O161.345 (4)C211—O261.338 (4)
C111—C12'1.497 (4)C211—C22'1.456 (5)
C112—O161.453 (4)C212—O261.452 (4)
C112—H12A0.9800C212—H12D0.9800
C112—H12B0.9800C212—H12E0.9800
C112—H12C0.9800C212—H12F0.9800
C113—H13A0.9800C213—H13D0.9800
C113—H13B0.9800C213—H13E0.9800
C113—H13C0.9800C213—H13F0.9800
C12'—C13'1.338 (4)C22'—C23'1.373 (4)
C13'—C14'1.475 (5)C23'—C24'1.466 (5)
C13'—H13'0.9500C23'—H23'0.9500
C14'—O151.227 (4)C24'—O251.233 (4)
C14'—C15'1.445 (4)C24'—C25'1.450 (5)
C15'—C16'1.340 (4)C25'—C26'1.357 (5)
C15'—H15'0.9500C25'—H25'0.9500
C16'—O181.332 (4)C26'—O281.319 (4)
O12—H120.8400O22—H220.8400
O27···Cl123.070 (3)O23···Cl21i3.006 (3)
O11—C12—C12'110.2 (2)O21—C22—C22'109.2 (3)
O11—C12—C16'108.6 (2)O21—C22—C26'108.7 (3)
C12'—C12—C16'113.5 (2)C22'—C22—C26'115.3 (3)
O11—C12—C13104.7 (2)O21—C22—C23103.8 (2)
C12'—C12—C13110.8 (2)C22'—C22—C23111.1 (3)
C16'—C12—C13108.6 (2)C26'—C22—C23108.0 (3)
O13—C13—C19130.5 (3)O23—C23—C29130.4 (3)
O13—C13—C12124.5 (3)O23—C23—C22124.5 (3)
C19—C13—C12104.9 (2)C29—C23—C22105.0 (3)
O12—C14—C19124.0 (3)O22—C24—C25121.6 (3)
O12—C14—C15119.5 (3)O22—C24—C29120.9 (3)
C19—C14—C15116.5 (3)C25—C24—C29117.5 (3)
C14—C15—C16122.3 (3)C24—C25—C26122.6 (3)
C14—C15—Cl12117.4 (2)C24—C25—Cl22117.5 (3)
C16—C15—Cl12120.3 (2)C26—C25—Cl22119.8 (3)
C17—C16—C15119.5 (3)C25—C26—C27117.9 (3)
C17—C16—C113119.8 (3)C25—C26—C213121.3 (3)
C15—C16—C113120.7 (3)C27—C26—C213120.7 (4)
C18—C17—C16118.7 (3)C28—C27—C26119.3 (3)
C18—C17—Cl11119.0 (2)C28—C27—Cl21119.3 (3)
C16—C17—Cl11122.3 (2)C26—C27—Cl21121.4 (3)
O11—C18—C17123.5 (3)O21—C28—C29114.0 (3)
O11—C18—C19115.2 (2)O21—C28—C27124.8 (3)
C17—C18—C19121.2 (3)C29—C28—C27121.1 (3)
C18—C19—C14121.8 (3)C28—C29—C24121.4 (3)
C18—C19—C13106.9 (3)C28—C29—C23108.6 (3)
C14—C19—C13131.3 (3)C24—C29—C23129.8 (3)
O18—C110—H10A109.5O28—C210—H10D109.5
O18—C110—H10B109.5O28—C210—H10E109.5
H10A—C110—H10B109.5H10D—C210—H10E109.5
O18—C110—H10C109.5O28—C210—H10F109.5
H10A—C110—H10C109.5H10D—C210—H10F109.5
H10B—C110—H10C109.5H10E—C210—H10F109.5
O17—C111—O16125.2 (3)O27—C211—O26122.1 (3)
O17—C111—C12'123.6 (3)O27—C211—C22'124.1 (3)
O16—C111—C12'111.1 (3)O26—C211—C22'113.8 (3)
O16—C112—H12A109.5O26—C212—H12D109.5
O16—C112—H12B109.5O26—C212—H12E109.5
H12A—C112—H12B109.5H12D—C212—H12E109.5
O16—C112—H12C109.5O26—C212—H12F109.5
H12A—C112—H12C109.5H12D—C212—H12F109.5
H12B—C112—H12C109.5H12E—C212—H12F109.5
C16—C113—H13A109.5C26—C213—H13D109.5
C16—C113—H13B109.5C26—C213—H13E109.5
H13A—C113—H13B109.5H13D—C213—H13E109.5
C16—C113—H13C109.5C26—C213—H13F109.5
H13A—C113—H13C109.5H13D—C213—H13F109.5
H13B—C113—H13C109.5H13E—C213—H13F109.5
C13'—C12'—C111123.3 (3)C23'—C22'—C211121.9 (3)
C13'—C12'—C12121.5 (3)C23'—C22'—C22122.2 (3)
C111—C12'—C12115.0 (3)C211—C22'—C22115.7 (3)
C12'—C13'—C14'122.2 (3)C22'—C23'—C24'120.7 (3)
C12'—C13'—H13'118.9C22'—C23'—H23'119.6
C14'—C13'—H13'118.9C24'—C23'—H23'119.6
O15—C14'—C15'122.7 (3)O25—C24'—C25'122.2 (3)
O15—C14'—C13'119.6 (3)O25—C24'—C23'118.9 (3)
C15'—C14'—C13'117.6 (3)C25'—C24'—C23'118.9 (3)
C16'—C15'—C14'120.6 (3)C26'—C25'—C24'121.6 (3)
C16'—C15'—H15'119.7C26'—C25'—H25'119.2
C14'—C15'—H15'119.7C24'—C25'—H25'119.2
O18—C16'—C15'126.4 (3)O28—C26'—C25'128.1 (3)
O18—C16'—C12109.9 (2)O28—C26'—C22110.8 (3)
C15'—C16'—C12123.6 (3)C25'—C26'—C22121.1 (3)
C18—O11—C12107.8 (2)C28—O21—C22108.0 (2)
C14—O12—H12109.5C24—O22—H22109.5
C111—O16—C112113.0 (3)C211—O26—C212114.8 (3)
C16'—O18—C110118.0 (3)C26'—O28—C210116.5 (3)
O11—C12—C13—O13−178.3 (3)O21—C22—C23—O23−174.8 (3)
C12'—C12—C13—O13−59.4 (4)C22'—C22—C23—O23−57.5 (5)
C16'—C12—C13—O1365.9 (4)C26'—C22—C23—O2369.9 (4)
O11—C12—C13—C195.1 (3)O21—C22—C23—C297.8 (3)
C12'—C12—C13—C19123.9 (3)C22'—C22—C23—C29125.1 (3)
C16'—C12—C13—C19−110.8 (3)C26'—C22—C23—C29−107.5 (3)
O12—C14—C15—C16−179.0 (3)O22—C24—C25—C26176.6 (3)
C19—C14—C15—C16−0.7 (4)C29—C24—C25—C26−2.5 (5)
O12—C14—C15—Cl120.0 (4)O22—C24—C25—Cl22−2.2 (5)
C19—C14—C15—Cl12178.3 (2)C29—C24—C25—Cl22178.7 (3)
C14—C15—C16—C17−0.8 (5)C24—C25—C26—C271.1 (5)
Cl12—C15—C16—C17−179.8 (2)Cl22—C25—C26—C27179.9 (3)
C14—C15—C16—C113178.6 (3)C24—C25—C26—C213−178.4 (3)
Cl12—C15—C16—C113−0.3 (4)Cl22—C25—C26—C2130.4 (5)
C15—C16—C17—C181.0 (4)C25—C26—C27—C281.6 (5)
C113—C16—C17—C18−178.4 (3)C213—C26—C27—C28−178.9 (3)
C15—C16—C17—Cl11−179.0 (2)C25—C26—C27—Cl21−176.3 (3)
C113—C16—C17—Cl111.6 (4)C213—C26—C27—Cl213.2 (5)
C16—C17—C18—O11−179.9 (3)C26—C27—C28—O21179.7 (3)
Cl11—C17—C18—O110.1 (4)Cl21—C27—C28—O21−2.4 (5)
C16—C17—C18—C190.3 (5)C26—C27—C28—C29−2.8 (5)
Cl11—C17—C18—C19−179.7 (2)Cl21—C27—C28—C29175.1 (3)
O11—C18—C19—C14178.2 (3)O21—C28—C29—C24179.2 (3)
C17—C18—C19—C14−2.0 (5)C27—C28—C29—C241.4 (5)
O11—C18—C19—C13−2.7 (3)O21—C28—C29—C233.7 (4)
C17—C18—C19—C13177.0 (3)C27—C28—C29—C23−174.1 (3)
O12—C14—C19—C18−179.7 (3)O22—C24—C29—C28−177.9 (3)
C15—C14—C19—C182.1 (4)C25—C24—C29—C281.2 (5)
O12—C14—C19—C131.5 (5)O22—C24—C29—C23−3.4 (6)
C15—C14—C19—C13−176.6 (3)C25—C24—C29—C23175.7 (3)
O13—C13—C19—C18−178.0 (3)O23—C23—C29—C28175.8 (4)
C12—C13—C19—C18−1.7 (3)C22—C23—C29—C28−7.0 (4)
O13—C13—C19—C140.9 (6)O23—C23—C29—C240.8 (7)
C12—C13—C19—C14177.2 (3)C22—C23—C29—C24178.0 (3)
O17—C111—C12'—C13'−156.1 (4)O27—C211—C22'—C23'−161.0 (3)
O16—C111—C12'—C13'22.4 (4)O26—C211—C22'—C23'18.3 (4)
O17—C111—C12'—C1217.6 (5)O27—C211—C22'—C2213.7 (5)
O16—C111—C12'—C12−163.9 (3)O26—C211—C22'—C22−166.9 (3)
O11—C12—C12'—C13'−132.9 (3)O21—C22—C22'—C23'−126.1 (3)
C16'—C12—C12'—C13'−10.9 (4)C26'—C22—C22'—C23'−3.3 (4)
C13—C12—C12'—C13'111.6 (3)C23—C22—C22'—C23'120.0 (3)
O11—C12—C12'—C11153.3 (3)O21—C22—C22'—C21159.2 (3)
C16'—C12—C12'—C111175.3 (2)C26'—C22—C22'—C211−178.1 (3)
C13—C12—C12'—C111−62.2 (3)C23—C22—C22'—C211−54.7 (4)
C111—C12'—C13'—C14'177.4 (3)C211—C22'—C23'—C24'175.1 (3)
C12—C12'—C13'—C14'4.2 (5)C22—C22'—C23'—C24'0.7 (5)
C12'—C13'—C14'—O15−175.6 (3)C22'—C23'—C24'—O25−178.3 (3)
C12'—C13'—C14'—C15'4.8 (5)C22'—C23'—C24'—C25'0.7 (5)
O15—C14'—C15'—C16'174.3 (3)O25—C24'—C25'—C26'180.0 (3)
C13'—C14'—C15'—C16'−6.1 (4)C23'—C24'—C25'—C26'1.0 (5)
C14'—C15'—C16'—O18−178.0 (3)C24'—C25'—C26'—O28178.8 (3)
C14'—C15'—C16'—C12−1.4 (4)C24'—C25'—C26'—C22−3.9 (5)
O11—C12—C16'—O18−50.3 (3)O21—C22—C26'—O28−54.3 (3)
C12'—C12—C16'—O18−173.2 (2)C22'—C22—C26'—O28−177.3 (3)
C13—C12—C16'—O1863.0 (3)C23—C22—C26'—O2857.7 (3)
O11—C12—C16'—C15'132.6 (3)O21—C22—C26'—C25'128.0 (3)
C12'—C12—C16'—C15'9.7 (4)C22'—C22—C26'—C25'5.0 (4)
C13—C12—C16'—C15'−114.0 (3)C23—C22—C26'—C25'−120.0 (3)
C17—C18—O11—C12−173.5 (3)C29—C28—O21—C221.8 (4)
C19—C18—O11—C126.3 (3)C27—C28—O21—C22179.5 (3)
C12'—C12—O11—C18−125.9 (3)C22'—C22—O21—C28−124.5 (3)
C16'—C12—O11—C18109.2 (2)C26'—C22—O21—C28108.9 (3)
C13—C12—O11—C18−6.7 (3)C23—C22—O21—C28−5.9 (3)
O17—C111—O16—C1128.3 (5)O27—C211—O26—C2123.4 (5)
C12'—C111—O16—C112−170.2 (3)C22'—C211—O26—C212−176.0 (3)
C15'—C16'—O18—C110−5.3 (5)C25'—C26'—O28—C2101.7 (5)
C12—C16'—O18—C110177.8 (3)C22—C26'—O28—C210−175.8 (3)
Symmetry code: (i) −x+1, y+1/2, −z+2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O12—H12···O15ii0.842.332.916 (3)128
O12—H12···O130.842.503.149 (3)135
O22—H22···O230.842.363.021 (4)136
Symmetry code: (ii) −x, y−1/2, −z+1.

Experimental details

Crystal data
Chemical formulaC17H12Cl2O7
Mr399.17
Crystal system, space groupMonoclinic, P21
Temperature (K)120
a, b, c (Å)8.9276 (3), 11.3625 (4), 16.5006 (6)
β (°) 94.456 (1)
V (Å3)1668.76 (10)
Z4
Radiation typeMo Kα
µ (mm−1)0.43
Crystal size (mm)0.25 × 0.15 × 0.08
Data collection
DiffractometerBruker SMART platform CCD
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2000)
Tmin, Tmax0.82, 0.97
No. of measured, independent and
observed [I > 2σ(I)] reflections		22828, 8165, 7496
Rint0.029
(sin θ/λ)max (Å−1)0.667
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.053, 0.145, 1.06
No. of reflections8165
No. of parameters480
No. of restraints1
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.81, −0.36
Absolute structureFlack (1983), ???? Friedel pairs
Absolute structure parameter0.04 (6)

Computer programs: SMART and SAINT (Bruker, 1998), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2006), enCIFer (Allen et al., 2004).

Selected interatomic distances (Å) top
O27···Cl123.070 (3)O23···Cl21i3.006 (3)
Symmetry code: (i) −x+1, y+1/2, −z+2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O12—H12···O15ii0.842.332.916 (3)128
O12—H12···O130.842.503.149 (3)135
O22—H22···O230.842.363.021 (4)136
Symmetry code: (ii) −x, y−1/2, −z+1.
 

Acknowledgements

We thank the Danish Instrument Center for NMR Spectroscopy of Biological Macromolecules for NMR time. We thank the Danish Research Council (reference No. 274-07-0561) for financial support (MHR) and the Faculty of Life Sciences, University of Copenhagen, for scholarship financing for MTN.

References

First citationAllen, F. H., Johnson, O., Shields, G. P., Smith, B. R. & Towler, M. (2004). J. Appl. Cryst. 37, 335–338.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationBarton, D. H. R. & Scott, A. I. (1958). J. Chem. Soc. pp. 1767–1772.  CrossRef Web of Science Google Scholar
 First citationBrown, W. A. C. & Sim, G. A. (1963). J. Chem. Soc. pp. 1050–1059.  CrossRef Web of Science Google Scholar
 First citationBruker (1998). SMART and SAINT. Versions 5.054. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
 First citationBruker (2000). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
 First citationCalam, C. T., Clutterbuck, P. W., Oxford, A. E. & Raistrick, H. (1939). Biochem. J. 33, 579–588.  PubMed Google Scholar
 First citationCalam, C. T., Clutterbuck, P. W., Oxford, A. E. & Raistrick, H. (1947). Biochem. J. 41, 458–462.  Google Scholar
 First citationChooi, Y. H., Cacho, R. & Tang, Y. (2010). Chem. Biol. 17, 483–494.  Web of Science CrossRef CAS PubMed Google Scholar
 First citationChu, M., Mierzwa, R., Truumees, I., King, A., Sapidou, E., Barrabee, E., Terracciano, J., Patel, M. G., Gullo, V. P., Burrier, R., Das, P. R., Mittelman, S. & Puar, M. S. (1997). Tetrahedron Lett. 38, 6111–6114.  CrossRef CAS Web of Science Google Scholar
 First citationClutterbuck, P. W., Koerber, W. & Raistrick, H. (1937). Biochem. J. 31, 1089–1092.  PubMed CAS Google Scholar
 First citationFarrugia, L. J. (1997). J. Appl. Cryst. 30, 565.  CrossRef IUCr Journals Google Scholar
 First citationFlack, H. D. (1983). Acta Cryst. A39, 876–881.  CrossRef CAS Web of Science IUCr Journals Google Scholar
 First citationFujii, I., Iijima, H., Ebizuka, Y. & Sankawa, U. (1983). Chem. Pharm. Bull. 31, 337–340.  CrossRef CAS Google Scholar
 First citationGrove, J. F., MacMillan, J., Mulholland, T. P. C. & Rogers, M. A. T. (1952). J. Chem. Soc. pp. 3977–3987.  CrossRef Web of Science Google Scholar
 First citationHo, Y. S., Duh, J. S., Jeng, J. H., Wang, Y. J., Liang, Y. C., Lin, C. H., Tseng, C. J., Yu, C. F., Chen, R. J. & Lin, J. K. (2001). Int. J. Cancer, 91, 393–401.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationKatoh, T. & Ohmori, O. (2000). Tetrahedron Lett. 41, 465–469.  Web of Science CrossRef CAS Google Scholar
 First citationKatoh, T., Ohmori, O., Iwasaki, K. & Inoue, M. (2002). Tetrahedron, 58, 1289–1299.  Web of Science CrossRef CAS Google Scholar
 First citationMacMillan, J. (1959). J. Chem. Soc. pp. 1823–1830.  CrossRef Web of Science Google Scholar
 First citationMacrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationPanda, D., Rathinasamy, K., Santra, M. K. & Wilson, L. (2005). Proc. Natl Acad. Sci. USA, 102, 9878–9883.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationPuttaraja, Nirmala, K. A., Sakegowda, D. S. & Duax, W. L. (1982). J. Crystallogr. Spectrosc. Res. 12, 415–423.  CSD CrossRef CAS Web of Science Google Scholar
 First citationRaistrick, H. & Smith, G. (1936). Biochem. J. 30, 1315–1322.  PubMed CAS Google Scholar
 First citationRebacz, B., Larsen, T. O., Clausen, M. H., Rønnest, M. H., Löffler, H., Ho, A. D. & Krämer, A. (2007). Cancer Res. 67, 6342–6350.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationRinderknecht, H., Ward, J. L., Bergel, F. & Morrison, A. L. (1947). Biochem. J. 41, 463–469.  CAS Google Scholar
 First citationRønnest, M. H., Rebacz, B., Markworth, L., Terp, A. H., Larsen, T. O., Krämer, A. & Clausen, M. H. (2009). J. Med. Chem. 52, 3342–3347.  Web of Science PubMed Google Scholar
 First citationSato, S., Okusa, N., Ogawa, A., Ikenoue, T., Seki, T. & Tsuji, T. (2005). J. Antibiot. 58, 583–589.  CrossRef PubMed CAS Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationShinohara, C., Chikanishi, T., Nakashima, S., Hashimoto, A., Hamanaka, A., Endo, A. & Hasumi, K. (2000). J. Antibiot. 53, 262–268.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationTakatsuki, A., Suzuki, S., Ando, K., Tamura, G. & Arima, K. (1969). Agric. Biol. Chem. Tokyo, 33, 1119–1123.  CrossRef CAS Google Scholar
 First citationTakatsuki, A., Yamaguchi, I., Tamura, G., Misato, T. & Arima, K. (1969). J. Antibiot. 22, 442–445.  CrossRef CAS PubMed Web of Science Google Scholar

© International Union of Crystallography. Prior permission is not required to reproduce short quotations, tables and figures from this article, provided the original authors and source are cited. For more information, click here.

Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296
Volume 67| Part 3| March 2011| Pages o125-o128
doi:10.1107/S0108270111005816
Follow Acta Cryst. C
Sign up for e-alerts
E-alerts
Follow Acta Cryst. on Twitter
Twitter
Follow us on facebook
Facebook
Sign up for RSS feeds
RSS