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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 64| Part 7| July 2008| Pages o1370-o1371

Unusual hemiacetal structure derived from Salvinorin A

aDepartment of Medicinal Chemistry, University of Mississippi, 417 Faser Hall, University, MS 38677, USA, bDepartment of Pharmacognosy, University of Mississippi, PO Box 1848, 443 Faser Hall, University, MS, 38677-1848, USA, cNational Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA, and dDepartment of Chemistry and Biochemistry, University of Mississippi, University, MS 38677, USA
*Correspondence e-mail: mavery@olemiss.edu

(Received 11 December 2007; accepted 14 January 2008; online 28 June 2008)

The salvinorin A analog dimethyl (2R,3aR,4R,6aR,7R,9S,9aS,9bS)-2-(3-fur­yl)-9,9a-dihydr­oxy-3a,6a-dimethyl­dodeca­hydro­benzo[de]chromene-4,7-dicarboxyl­ate, C22H30O8, has a relatively simple spatial arrangement in which mol­ecules are linked into layers by two pairs of O—H⋯O hydrogen bonds. Each mol­ecule has as the central feature a dodeca­hydro-1H-phenalene ring system. Its three six-membered rings are in the chair conformation, with two axial methyl groups, one axial OH, and one equatorial OH, these OH groups being directly responsible for linking of the mol­ecules in the crystal structure.

Related literature

For the synthesis of analogs of salvinorin A, see: Bikbulatov et al. (2007[Bikbulatov, R. V., Yan, F., Roth, B. L. & Zjawiony, J. K. (2007). Biorg. Med. Chem. Lett., 17, 2229-2232.]); Lee et al. (2006[Lee, D. Y. W., He, M., Liu-Chen, L.-Y., Wang, Y., Li, J.-G., Xu, W., Ma, Z., Carlezon, W. A. Jr & Cohen, B. (2006). Biorg. Med. Chem. Lett. 16, 5498-5502.]); Beguin et al. (2006[Beguin, C., Richards, M. R., Li, J.-G., Wang, Y., Xu, W., Liu-Chen, L.-Y., Carlezon, W. A. & Cohen, B. M. (2006). Biorg. Med. Chem. Lett. 16, 4679-4685.]); Stewart et al. (2006[Stewart, D. J., Fahmy, H., Roth, B. L., Yan, F. & Zjawiony, J. K. (2006). Arzneim.- Forsch. Drug Res. 56, 269-275.]) and references cited therein. For modifications of salvinorin A with changed pharmacological profile, see: Rothman et al. (2007[Rothman, R. B., Murphy, D. L., Xu, H., Godin, J. A., Dersch, C. M., Partilla, J. S., Tidgewell, K., Schmidt, M. & Prisinzano, T. E. (2007). J. Pharmacol. Exp. Ther. 320, 801-810.]); Groer et al. (2007[Groer, C. E., Tidgewell, K., Moyer, R. A., Harding, W. W., Rothman, R. B., Prisinzano, T. E. & Bohn, L. M. (2007). Mol. Pharmacol. 71, 549-557.]); Tidgewell et al. (2006[Tidgewell, K., Harding, W. W., Lozama, A., Cobb, H., Shah, K., Kannan, P., Dersch, C. M., Parrish, D., Deschamps, J. R., Rothman, R. B. & Prisinzano, T. E. (2006). J. Nat. Prod. 69, 914-918.]); Harding et al. (2005[Harding, W. W., Tidgewell, K., Schmidt, M., Shah, K., Dersch, C. M., Snyder, J., Parrish, D., Deschamps, J. R., Rothman, R. B. & Prisinzano, T. E. (2005). Org. Lett. 7, 3017-3020.], 2006[Harding, W. W., Schmidt, M., Tidgewell, K., Kannan, P., Holden, K. G., Gilmour, B., Navarro, H., Rothman, R. B. & Prisinzano, T. E. (2006). J. Nat. Prod. 69, 107-112.]).

[Scheme 1]

Experimental

Crystal data
  • C22H30O8

  • Mr = 422.46

  • Monoclinic, P 21

  • a = 11.6801 (5) Å

  • b = 6.0522 (3) Å

  • c = 15.3739 (6) Å

  • β = 107.678 (2)°

  • V = 1035.47 (8) Å3

  • Z = 2

  • Cu Kα radiation

  • μ = 0.86 mm−1

  • T = 296 (2) K

  • 0.32 × 0.15 × 0.13 mm

Data collection
  • Bruker SMART CCD area-detector diffractometer

  • Absorption correction: none

  • 18724 measured reflections

  • 3726 independent reflections

  • 3615 reflections with I > 2σ(I)

  • Rint = 0.037

Refinement
  • R[F2 > 2σ(F2)] = 0.037

  • wR(F2) = 0.096

  • S = 1.05

  • 3726 reflections

  • 277 parameters

  • 1 restraint

  • H-atom parameters constrained

  • Δρmax = 0.41 e Å−3

  • Δρmin = −0.21 e Å−3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 1587 Friedel pairs

  • Flack parameter: 0.14 (18)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O3—H3⋯O2i 0.82 1.99 2.757 (2) 155
O2—H2A⋯O1i 0.82 2.07 2.787 (2) 146
Symmetry code: (i) [-x+1, y-{\script{1\over 2}}, -z+2].

Data collection: SMART (Bruker, 2003[Bruker (2003). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2003[Bruker (2003). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: 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: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

.

The structure was solved using Direct methods and difference Fourier techniques SHELXTL, V6.12 (Sheldrick, 2008). Hydrogen atoms were placed in their expected chemical positions using the HFIX command and were included in the final cycles of least squares with isotropic Uij related to the atoms ridden upon. All non-hydrogen atoms were refined anisotropically.Structure solution, refinement, graphics and generation of publication materials were performed by using SHELXTL, V6.12 software. Additional details of data collection and structure refinement are given in Table 1.

Related literature top

For the synthesis of analogs of salvinorin A, see: Bikbulatov et al. (2007); Lee et al. (2006); Beguin et al. (2006); Stewart et al. (2006) and other references cited therein. For modifications of salvinorin A with changed pharmacological profile, see: Rothman et al. (2007); Groer et al. (2007); Tidgewell et al. (2006); Harding et al. (2005, 2006).

Experimental top

Synthesis of hemiacetal (2): Salvinorin A (10 mg, 23 mmol) was placed in aqueous 5% KOH (5 ml) and refluxed for two hours producing a yellow solution. Upon reaching room temperature, the solution was cooled in an ice bath and neutralized with cold aqueous 0.5M HCl. The resulting precipitate was collected by vacuum filtration. The product was purified by passing through a short silica column eluting with ethyl acetate to yield 6.2 mg of 1a (69%).

1 ml of TMSCHN2 (0.13 mmol) in benzene was added at room temperature to a solution of 1a (20 mg, 0.05 mmol) in methanol (5 ml). The mixture was stirred at room temperature for 30 min and concentrated to give the corresponding dimethyl ester 2. The product was purified by column chromatography using hexanes: ethyl acetate (2:1) for elution. Yield 18.3 mg (87%).

Crystals of dimethyl (2R,3aR,4R,6aR,7R,9S,9aS,9 bS)-2-(3-furyl)-9,9a-dihydroxy-3a,6a-dimethyldodecahydrobenzo[de]chromene-4,7-dicarboxylate (2) were obtained from slow evaporation of a solution in ethyl acetate/hexanes 1:9. A suitable crystal was coated with Paratone N oil, suspended in a CryoLoop (Hampton Research) and placed in a cooled nitrogen gas stream at 100 K on a Bruker D8 APEX II CCD sealed tube diffractometer with graphite monochromated Cu Ka (1.54178 Å) radiation. Data were measured using a series of combinations of phi and omega scans with 10 s frame exposures and 0.5o frame widths. Data collection, indexing and initial cell refinements were all carried out using APEX II software (Bruker, 2003).Frame integration and final cell refinements were done using SAINT (Bruker, 2003) software. The final cell parameters were determined from least-squares refinement on 3446 reflections

Considering that the Flack parameter (Flack, 1983) does not confirm unambiguously the absolute configuration of the molecule, The chiral centers were assigned based in the original known configuration of the starting material, Salvinorin A.

Refinement top

All H atoms were located in difference maps and treated as riding atoms, with the following distance restraints: C—H = 0.93 Å, Uiso=1.2Ueq (C) for Csp2, C—H = 0.98 Å, Uiso = 1.2Ueq (C) for CH, C—H = 0.97 Å, Uiso = 1.2Ueq (C) for CH2, C—H = 0.96 Å, Uiso = 1.5Ueq (C) for CH3, O—H = 0.82 Å, Uiso = 1.5Ueq (O) for OH.

Computing details top

Data collection: SMART (Bruker, 2003); cell refinement: SMART (Bruker, 2003); data reduction: SAINT (Bruker, 2003); 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 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Molecular projection, showing the atom-labeling scheme. H atoms were ommited to allow better visualization.
[Figure 2] Fig. 2. The packing in the crystal structure, showing the O—H···O hydrogen bonds as dashed blue lines.
[Figure 3] Fig. 3. Synthesis of the title compound
dimethyl (2R,3aR,4R,6aR,7R,9S,9aS,9bS)-2-(3-furyl)-9,9a-dihydroxy-3a,6a-dimethyldodecahydrobenzo[de]chromene-4,7-dicarboxylate top
Crystal data top
C22H30O8F(000) = 452
Mr = 422.46Dx = 1.355 Mg m3
Monoclinic, P21Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2ybCell parameters from 8551 reflections
a = 11.6801 (5) Åθ = 3.0–69.4°
b = 6.0522 (3) ŵ = 0.86 mm1
c = 15.3739 (6) ÅT = 296 K
β = 107.678 (2)°Blocks, colourless
V = 1035.47 (8) Å30.32 × 0.15 × 0.13 mm
Z = 2
Data collection top
Bruker SMART CCD area-detector
diffractometer
3615 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube, Siemens KFF Cu 2 K90Rint = 0.037
Graphite monochromatorθmax = 69.4°, θmin = 3.0°
phi and ω scansh = 1313
18724 measured reflectionsk = 77
3726 independent reflectionsl = 1818
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.037H-atom parameters constrained
wR(F2) = 0.096 w = 1/[σ2(Fo2) + (0.0458P)2 + 0.4492P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max < 0.001
3726 reflectionsΔρmax = 0.42 e Å3
277 parametersΔρmin = 0.21 e Å3
1 restraintAbsolute structure: Flack (1983), 1587 Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.14 (18)
Crystal data top
C22H30O8V = 1035.47 (8) Å3
Mr = 422.46Z = 2
Monoclinic, P21Cu Kα radiation
a = 11.6801 (5) ŵ = 0.86 mm1
b = 6.0522 (3) ÅT = 296 K
c = 15.3739 (6) Å0.32 × 0.15 × 0.13 mm
β = 107.678 (2)°
Data collection top
Bruker SMART CCD area-detector
diffractometer
3615 reflections with I > 2σ(I)
18724 measured reflectionsRint = 0.037
3726 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.037H-atom parameters constrained
wR(F2) = 0.096Δρmax = 0.42 e Å3
S = 1.05Δρmin = 0.21 e Å3
3726 reflectionsAbsolute structure: Flack (1983), 1587 Friedel pairs
277 parametersAbsolute structure parameter: 0.14 (18)
1 restraint
Special details top

Experimental. The structure was solved using Direct methods and difference Fourier techniques SHELXTL, V6.12 (Bruker, 2003). Hydrogen atoms were placed in their expected chemical positions using the HFIX command and were included in the final cycles of least squares with isotropic Uij related to the atoms ridden upon. All non-hydrogen atoms were refined anisotropically.Structure solution, refinement, graphics and generation of publication materials were performed by using SHELXTL, V6.12 software. Additional details of data collection and structure refinement are given in Table 1.

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
C20.18522 (17)0.9011 (4)0.91971 (13)0.0308 (5)
H20.15710.74820.91840.037*
C50.15034 (17)0.9159 (3)0.58226 (12)0.0226 (4)
H5A0.11710.76900.56680.027*
H5B0.12261.00760.52820.027*
C30.12566 (17)1.0070 (4)0.82782 (12)0.0261 (4)
H3A0.15521.15680.82810.031*
H3B0.03961.01440.81760.031*
C60.28737 (16)0.9033 (3)0.61198 (12)0.0217 (4)
H6A0.31951.05210.62240.026*
H6B0.31220.84010.56260.026*
C40.10549 (16)1.0123 (3)0.65832 (12)0.0209 (4)
H40.13801.16220.67110.025*
C80.54094 (17)0.7152 (4)0.82950 (13)0.0283 (4)
H8A0.52860.55680.83020.034*
H8B0.62680.74280.84720.034*
C90.48763 (17)0.8258 (3)0.89657 (12)0.0256 (4)
H90.49710.98570.89140.031*
C70.48158 (17)0.8048 (3)0.73302 (12)0.0230 (4)
H70.49500.96480.73490.028*
C3A0.15070 (16)0.8761 (3)0.74901 (11)0.0202 (4)
C6A0.34211 (16)0.7655 (3)0.69886 (12)0.0197 (4)
C9A0.35251 (18)0.7770 (3)0.87112 (13)0.0239 (4)
C9B0.29098 (16)0.8644 (3)0.77341 (11)0.0191 (4)
H9B0.31541.01980.77670.023*
C100.16237 (19)1.0186 (5)0.99865 (14)0.0448 (7)
C120.1441 (3)1.0759 (8)1.13703 (17)0.0705 (12)
H120.14331.05391.19670.085*
C110.1675 (3)0.9226 (8)1.0830 (2)0.0778 (12)
H110.18460.77511.09850.093*
C130.1359 (3)1.2334 (7)1.00599 (18)0.0751 (12)
H130.12811.34140.96150.090*
C160.03024 (17)1.0299 (3)0.62641 (12)0.0252 (4)
C180.54524 (17)0.7069 (4)0.66942 (13)0.0261 (4)
C140.08432 (17)0.6535 (3)0.73785 (13)0.0257 (4)
H14A0.12700.55480.78560.039*
H14B0.08010.59060.67960.039*
H14C0.00450.67630.74140.039*
C150.31545 (17)0.5190 (3)0.67784 (13)0.0259 (4)
H15A0.23160.50000.64600.039*
H15B0.33590.43700.73390.039*
H15C0.36230.46610.64050.039*
C190.6056 (3)0.7648 (5)0.53744 (18)0.0490 (7)
H19A0.68980.74270.56720.073*
H19B0.59510.87010.48900.073*
H19C0.56920.62700.51280.073*
C170.1957 (2)1.2172 (6)0.65095 (18)0.0505 (7)
H17A0.23221.24190.58680.076*
H17B0.21221.34040.68460.076*
H17C0.22791.08480.66880.076*
O10.31411 (11)0.9003 (3)0.93685 (8)0.0273 (3)
O30.32773 (13)0.5526 (2)0.87711 (9)0.0286 (3)
H30.37090.50300.92560.043*
O50.09773 (12)0.9134 (3)0.57030 (10)0.0352 (4)
O60.06776 (13)1.1939 (3)0.66985 (10)0.0349 (4)
O20.54549 (13)0.7663 (3)0.98856 (9)0.0311 (3)
H2A0.59350.66630.99020.047*
O70.58818 (15)0.5249 (3)0.67619 (11)0.0429 (4)
O80.54884 (15)0.8474 (3)0.60324 (11)0.0383 (4)
O40.1223 (2)1.2643 (7)1.09199 (17)0.1192 (16)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C20.0193 (9)0.0538 (13)0.0210 (9)0.0075 (10)0.0087 (7)0.0039 (9)
C50.0235 (9)0.0264 (9)0.0172 (8)0.0001 (8)0.0053 (7)0.0016 (7)
C30.0159 (9)0.0401 (11)0.0237 (9)0.0026 (8)0.0078 (7)0.0048 (9)
C60.0233 (9)0.0242 (9)0.0195 (8)0.0030 (8)0.0093 (7)0.0008 (7)
C40.0202 (9)0.0206 (9)0.0226 (9)0.0014 (7)0.0074 (7)0.0020 (7)
C80.0190 (9)0.0402 (12)0.0239 (9)0.0031 (8)0.0037 (8)0.0023 (8)
C90.0222 (10)0.0362 (11)0.0178 (8)0.0017 (8)0.0051 (7)0.0020 (8)
C70.0198 (9)0.0281 (10)0.0215 (9)0.0020 (8)0.0067 (7)0.0046 (7)
C3A0.0161 (9)0.0257 (9)0.0185 (8)0.0028 (7)0.0050 (7)0.0016 (7)
C6A0.0174 (9)0.0236 (9)0.0180 (8)0.0013 (7)0.0054 (7)0.0011 (7)
C9A0.0222 (10)0.0311 (10)0.0199 (8)0.0026 (8)0.0084 (7)0.0001 (8)
C9B0.0174 (9)0.0207 (9)0.0190 (8)0.0034 (7)0.0053 (7)0.0003 (7)
C100.0168 (10)0.098 (2)0.0218 (10)0.0058 (12)0.0089 (8)0.0109 (12)
C120.0373 (15)0.160 (4)0.0190 (11)0.0052 (19)0.0150 (10)0.0089 (18)
C110.082 (2)0.126 (3)0.0380 (15)0.036 (2)0.0370 (15)0.0145 (18)
C130.072 (2)0.120 (3)0.0285 (13)0.050 (2)0.0076 (13)0.0206 (16)
C160.0219 (9)0.0290 (10)0.0249 (9)0.0025 (8)0.0075 (8)0.0039 (8)
C180.0175 (9)0.0341 (11)0.0254 (9)0.0010 (8)0.0048 (7)0.0053 (8)
C140.0209 (9)0.0306 (10)0.0243 (9)0.0062 (8)0.0048 (7)0.0024 (8)
C150.0252 (10)0.0257 (10)0.0254 (9)0.0003 (8)0.0060 (8)0.0028 (8)
C190.0518 (16)0.0625 (17)0.0461 (13)0.0102 (13)0.0350 (12)0.0024 (13)
C170.0283 (11)0.0711 (18)0.0494 (14)0.0197 (12)0.0077 (11)0.0069 (13)
O10.0180 (7)0.0454 (8)0.0191 (6)0.0045 (6)0.0066 (5)0.0041 (6)
O30.0278 (7)0.0308 (7)0.0235 (6)0.0033 (6)0.0022 (5)0.0080 (6)
O50.0237 (7)0.0461 (9)0.0313 (7)0.0011 (7)0.0015 (6)0.0102 (7)
O60.0259 (7)0.0379 (8)0.0393 (8)0.0089 (7)0.0074 (6)0.0058 (7)
O20.0292 (8)0.0361 (8)0.0244 (7)0.0024 (6)0.0027 (6)0.0009 (6)
O70.0443 (9)0.0492 (10)0.0389 (8)0.0204 (8)0.0181 (7)0.0006 (8)
O80.0409 (9)0.0458 (10)0.0395 (8)0.0042 (7)0.0290 (7)0.0025 (7)
O40.0566 (14)0.244 (5)0.0456 (13)0.063 (2)0.0011 (11)0.063 (2)
Geometric parameters (Å, º) top
C2—O11.447 (2)C9A—O11.433 (2)
C2—C101.499 (3)C9A—C9B1.548 (2)
C2—C31.515 (3)C9B—H9B0.9800
C2—H20.9800C10—C131.349 (5)
C5—C61.527 (3)C10—C111.405 (4)
C5—C41.535 (2)C12—O41.318 (6)
C5—H5A0.9700C12—C111.328 (5)
C5—H5B0.9700C12—H120.9300
C3—C3A1.548 (3)C11—H110.9300
C3—H3A0.9700C13—O41.391 (3)
C3—H3B0.9700C13—H130.9300
C6—C6A1.540 (2)C16—O51.204 (2)
C6—H6A0.9700C16—O61.342 (3)
C6—H6B0.9700C18—O71.202 (3)
C4—C161.514 (2)C18—O81.336 (3)
C4—C3A1.567 (2)C14—H14A0.9600
C4—H40.9800C14—H14B0.9600
C8—C91.513 (3)C14—H14C0.9600
C8—C71.533 (3)C15—H15A0.9600
C8—H8A0.9700C15—H15B0.9600
C8—H8B0.9700C15—H15C0.9600
C9—O21.416 (2)C19—O81.456 (3)
C9—C9A1.535 (3)C19—H19A0.9600
C9—H90.9800C19—H19B0.9600
C7—C181.517 (3)C19—H19C0.9600
C7—C6A1.571 (2)C17—O61.440 (3)
C7—H70.9800C17—H17A0.9600
C3A—C141.538 (3)C17—H17B0.9600
C3A—C9B1.568 (2)C17—H17C0.9600
C6A—C151.538 (3)O3—H30.8200
C6A—C9B1.563 (2)O2—H2A0.8200
C9A—O31.398 (2)
O1—C2—C10106.57 (15)O3—C9A—O1110.13 (15)
O1—C2—C3109.20 (15)O3—C9A—C9112.80 (17)
C10—C2—C3114.2 (2)O1—C9A—C9103.77 (15)
O1—C2—H2108.9O3—C9A—C9B110.57 (15)
C10—C2—H2108.9O1—C9A—C9B110.73 (15)
C3—C2—H2108.9C9—C9A—C9B108.67 (15)
C6—C5—C4111.12 (14)C9A—C9B—C6A114.36 (15)
C6—C5—H5A109.4C9A—C9B—C3A113.02 (14)
C4—C5—H5A109.4C6A—C9B—C3A116.49 (14)
C6—C5—H5B109.4C9A—C9B—H9B103.6
C4—C5—H5B109.4C6A—C9B—H9B103.6
H5A—C5—H5B108.0C3A—C9B—H9B103.6
C2—C3—C3A111.77 (17)C13—C10—C11105.5 (3)
C2—C3—H3A109.3C13—C10—C2128.8 (3)
C3A—C3—H3A109.3C11—C10—C2125.6 (3)
C2—C3—H3B109.3O4—C12—C11108.6 (3)
C3A—C3—H3B109.3O4—C12—H12125.7
H3A—C3—H3B107.9C11—C12—H12125.7
C5—C6—C6A114.07 (15)C12—C11—C10109.2 (4)
C5—C6—H6A108.7C12—C11—H11125.4
C6A—C6—H6A108.7C10—C11—H11125.4
C5—C6—H6B108.7C10—C13—O4107.7 (3)
C6A—C6—H6B108.7C10—C13—H13126.1
H6A—C6—H6B107.6O4—C13—H13126.1
C16—C4—C5110.25 (14)O5—C16—O6123.23 (18)
C16—C4—C3A111.23 (15)O5—C16—C4125.74 (18)
C5—C4—C3A112.15 (15)O6—C16—C4111.03 (16)
C16—C4—H4107.7O7—C18—O8122.7 (2)
C5—C4—H4107.7O7—C18—C7125.1 (2)
C3A—C4—H4107.7O8—C18—C7112.15 (17)
C9—C8—C7110.12 (16)C3A—C14—H14A109.5
C9—C8—H8A109.6C3A—C14—H14B109.5
C7—C8—H8A109.6H14A—C14—H14B109.5
C9—C8—H8B109.6C3A—C14—H14C109.5
C7—C8—H8B109.6H14A—C14—H14C109.5
H8A—C8—H8B108.2H14B—C14—H14C109.5
O2—C9—C8113.43 (16)C6A—C15—H15A109.5
O2—C9—C9A110.34 (15)C6A—C15—H15B109.5
C8—C9—C9A110.20 (15)H15A—C15—H15B109.5
O2—C9—H9107.5C6A—C15—H15C109.5
C8—C9—H9107.5H15A—C15—H15C109.5
C9A—C9—H9107.5H15B—C15—H15C109.5
C18—C7—C8108.61 (16)O8—C19—H19A109.5
C18—C7—C6A112.77 (14)O8—C19—H19B109.5
C8—C7—C6A112.85 (15)H19A—C19—H19B109.5
C18—C7—H7107.4O8—C19—H19C109.5
C8—C7—H7107.4H19A—C19—H19C109.5
C6A—C7—H7107.4H19B—C19—H19C109.5
C14—C3A—C3109.09 (16)O6—C17—H17A109.5
C14—C3A—C4109.84 (14)O6—C17—H17B109.5
C3—C3A—C4109.53 (15)H17A—C17—H17B109.5
C14—C3A—C9B116.24 (16)O6—C17—H17C109.5
C3—C3A—C9B105.55 (14)H17A—C17—H17C109.5
C4—C3A—C9B106.38 (14)H17B—C17—H17C109.5
C15—C6A—C6109.81 (15)C9A—O1—C2113.84 (14)
C15—C6A—C9B115.31 (16)C9A—O3—H3109.5
C6—C6A—C9B106.15 (14)C16—O6—C17116.61 (17)
C15—C6A—C7109.91 (15)C9—O2—H2A109.5
C6—C6A—C7108.86 (15)C18—O8—C19115.88 (19)
C9B—C6A—C7106.57 (13)C12—O4—C13108.9 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O2i0.821.992.757 (2)155
O2—H2A···O1i0.822.072.787 (2)146
Symmetry code: (i) x+1, y1/2, z+2.

Experimental details

Crystal data
Chemical formulaC22H30O8
Mr422.46
Crystal system, space groupMonoclinic, P21
Temperature (K)296
a, b, c (Å)11.6801 (5), 6.0522 (3), 15.3739 (6)
β (°) 107.678 (2)
V3)1035.47 (8)
Z2
Radiation typeCu Kα
µ (mm1)0.86
Crystal size (mm)0.32 × 0.15 × 0.13
Data collection
DiffractometerBruker SMART CCD area-detector
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
18724, 3726, 3615
Rint0.037
(sin θ/λ)max1)0.607
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.037, 0.096, 1.05
No. of reflections3726
No. of parameters277
No. of restraints1
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.42, 0.21
Absolute structureFlack (1983), 1587 Friedel pairs
Absolute structure parameter0.14 (18)

Computer programs: SMART (Bruker, 2003), SAINT (Bruker, 2003), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O2i0.821.992.757 (2)155.3
O2—H2A···O1i0.822.072.787 (2)146.2
Symmetry code: (i) x+1, y1/2, z+2.
 

Acknowledgements

The authors thank Dr K. Hardcastle for his helpful advice. We also thank the Center for Disease Control and Prevention, USA, for providing financial assistance (CDC cooperative agreements 1UO1 CI000211–03 and1UO1 CI000362–01). This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program grant No. C06 Rr-14503–01 from the National Center for Research Resources, National Institutes of Health.

References

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Volume 64| Part 7| July 2008| Pages o1370-o1371
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