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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 68| Part 11| November 2012| Pages o3182-o3183

Cyclo­(-L-prolyl-L-valinyl-) from Burkholderia thailandensis MSMB43

aDepartment of Biological Sciences, Department of Chemistry and Biochemistry, University of Wisconsin–Milwaukee, PO Box 413, Milwaukee, WI 53201, USA
*Correspondence e-mail: wang35@uwm.edu, ycheng@uwm.edu

(Received 8 October 2012; accepted 15 October 2012; online 20 October 2012)

The title compound [systematic name: (3S,8aS)-3-isopropyl­hexa­hydro­pyrrolo­[1,2-a]pyrazine-1,4-dione], C10H16N2O2,, is a newly isolated cyclic dipeptide from Burkholderia thailandensis MSMB43. There are two independent mol­ecules in the asymmetric unit. Two C atoms and their attached H atoms in the five-membered ring of one of the mol­ecules are disordered over two sets of sites in a 0.715 (5):0.285 (5) ratio. The two independent mol­ecules have the same configuration and the absolute configurations of the chiral centers were determined based on the observation of anomalous dispersion. In the crystal, two types of N—H⋯O hydrogen bonds link pairs of independent mol­ecules.

Related literature

For general background to secondary metabolites from B. thailandensis, see: Knappe et al. (2008[Knappe, T. A., Linne, U., Zirah, S., Rebuffat, S., Xie, X. & Marahiel, M. A. (2008). J. Am. Chem. Soc. 130, 11446-11454.]); Nguyen et al. (2008[Nguyen, T., Ishida, K., Jenke-Kodama, H., Dittmann, E., Gurgui, C., Hochmuth, T., Taudien, S., Platzer, M., Hertweck, C. & Piel, J. (2008). Nat. Biotechnol. 26, 225-233.]); Seyedsayamdost et al. (2010[Seyedsayamdost, M. R., Chandler, J. R., Blodgett, J. A., Lima, P. S., Duerkop, B. A., Oinuma, K., Greenberg, E. P. & Clardy, J. (2010). Org. Lett. 12, 716-719.]); Ishida et al. (2010[Ishida, K., Lincke, T., Behnken, S. & Hertweck, C. (2010). J. Am. Chem. Soc. 132, 13966-13968.]); Klausmeyer et al. (2011[Klausmeyer, P., Shipley, S. M., Zuck, K. M. & McCloud, T. G. (2011). J. Nat. Prod. 74, 2039-2044.]); Biggins et al. (2011[Biggins, J. B., Gleber, C. D. & Brady, S. F. (2011). Org. Lett. 13, 1536-1539.]); Wang et al. (2011[Wang, C., Henkes, L. M., Doughty, L. B., He, M., Wang, D., Meyer-Almes, F. J. & Cheng, Y. Q. (2011). J. Nat. Prod. 74, 2031-2038.], 2012[Wang, C., Flemming, C. J. & Cheng, Y. Q. (2012). MedChemComm, 3, 976-981.]); Ishida et al. (2012[Ishida, K., Lincke, T. & Hertweck, C. (2012). Angew. Chem. Int. Ed. Engl. 51, 5470-5474.]). For isolation of the title compound from other microorganisms, see: Chen (1960[Chen, Y. S. (1960). Bull. Chem. Soc. Jpn, 24, 372-381.]); Schmitz et al. (1983[Schmitz, F. J., Vanderah, D. J., Hollenbeak, K. H., Enwall, C. E. L. & Gopichand, Y. (1983). J. Org. Chem. 48, 3941-3945.]); Jayatilake et al. (1996[Jayatilake, G. S., Thornton, M. P., Leonard, A. C., Grimwade, J. E. & Baker, B. J. (1996). J. Nat. Prod. 59, 293-296.]); Ginz & Engelhardt (2000[Ginz, M. & Engelhardt, U. H. (2000). J. Agric. Food Chem. 48, 3528-3532.]); Qi et al. (2009[Qi, S. H., Xu, Y., Gao, J., Qian, P. Y. & Zhang, S. (2009). Anna. Microbiol. 59, 229-233.]); Wang et al. (2010[Wang, J. H., Quan, C. S., Qi, X. H., Li, X. & Fan, S. D. (2010). Ann. Microbiol. 396, 1773-1779.]); Park et al. (2006[Park, Y. C., Gunasekera, S. P., Lopez, J. V., McCarthy, P. J. & Wright, A. E. (2006). J. Nat. Prod. 69, 580-584.]). For the biological activity of the title compound, see: Holden et al. (1999[Holden, M. T., Ram Chhabra, S., de Nys, R., Stead, P., Bainton, N. J., Hill, P. J., Manefield, M., Kumar, N., Labatte, M., England, D., Rice, S., Givskov, M., Salmond, G. P., Stewart, G. S., Bycroft, B. W., Kjelleberg, S. & Williams, P. (1999). Mol. Microbiol. 33, 1254-1266.]); Fdhila et al. (2003[Fdhila, F., Vazquez, V., Sanchez, J. L. & Riguera, R. (2003). J. Nat. Prod. 66, 1299-1301.]). For large-scale genome sequencing, see: Mukhopadhyay et al. (2010[Mukhopadhyay, S., Thomason, M. K., Lentz, S., Nolan, N., Willner, K., Gee, J. E., Glass, M. B., Inglis, T. J., Merritt, A., Levy, A., Sozhamannan, S., Mateczun, A. & Read, T. D. (2010). J. Bacteriol. 192, 6313-6314.]); Yu et al. (2006[Yu, Y., Kim, H. S., Chua, H. H., Lin, C. H., Sim, S. H., Lin, D., Derr, A., Engels, R., DeShazer, D., Birren, B., Nierman, W. C. & Tan, P. (2006). BMC Microbiol. 6, 46.]); Zhuo et al. (2012[Zhuo, Y., Liu, L., Wang, Q., Liu, X., Ren, B., Liu, M., Ni, P., Cheng, Y. Q. & Zhang, L. (2012). J. Bacteriol. 194, 4749-4750.]). For our work on obtaining natural products from B. thailandensis MSMB43, see: Liu et al. (2012[Liu, X.-Y., Wang, C. & Cheng, Y.-Q. (2012). Acta Cryst. E68, o2757-o2758.]).

[Scheme 1]

Experimental

Crystal data
  • C10H16N2O2

  • Mr = 196.25

  • Orthorhombic, P 21 21 21

  • a = 5.6227 (1) Å

  • b = 10.2571 (2) Å

  • c = 34.2115 (6) Å

  • V = 1973.07 (6) Å3

  • Z = 8

  • Cu Kα radiation

  • μ = 0.76 mm−1

  • T = 100 K

  • 0.22 × 0.14 × 0.10 mm

Data collection
  • Bruker APEXII area-detector diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2007[Bruker (2007). APEX2, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.851, Tmax = 0.928

  • 28285 measured reflections

  • 3668 independent reflections

  • 3354 reflections with I > 2σ(I)

  • Rint = 0.045

Refinement
  • R[F2 > 2σ(F2)] = 0.031

  • wR(F2) = 0.075

  • S = 1.02

  • 3668 reflections

  • 271 parameters

  • 3 restraints

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.30 e Å−3

  • Δρmin = −0.23 e Å−3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 1481 Friedel pairs

  • Flack parameter: 0.05 (17)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1⋯O1Ai 0.872 (19) 2.016 (19) 2.8734 (17) 167.7 (17)
N1A—H1A⋯O1ii 0.916 (19) 2.06 (2) 2.9710 (17) 172.3 (17)
Symmetry codes: (i) x-1, y, z; (ii) x+1, y, z.

Data collection: APEX2 (Bruker, 2007[Bruker (2007). APEX2, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2007[Bruker (2007). APEX2, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL and OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]); software used to prepare material for publication: SHELXTL and OLEX2.

Supporting information


Comment top

Many interesting compounds, including thailandamides A—B (Ishida et al., 2012, Nguyen et al., 2008, Ishida et al., 2010), capistruin (Knappe et al., 2008), bactobolins A—D (Seyedsayamdost et al., 2010), burkholdacs A—B (Biggins et al., 2011), spiruchostatin C (Klausmeyer et al., 2011) and thailandepsins A—F (Wang et al., 2011, Wang et al., 2012), were discovered from Burkholderia thailandensis E264 in recent years. In conjunction with large-scale genome sequencing (Mukhopadhyay et al., 2010, Zhuo et al., 2012, Yu et al., 2006), the Burkholderia species have drawn much attention due to their capabilities to produce novel compounds with antibacterial, antitumor and antiviral activities. As a result of our expanded natural product discovery from Burkholderia species, we have recently confirmed that B. thailandensis MSMB43 can produce high titers of FK228 in M8 medium (Liu et al., 2012). Here we report the crystal structure of a known dipeptide isolated from the culture broth of B. thailandensis MSMB43 grown in M11 medium.

The title compound is a cyclic dipeptide of L-proline and L-valine. The structural skeleton is fused by a five-membered pyrrolidine ring and a six-membered piperazine ring. The pyrrolidine ring adopts an envelope configuration and the piperazine ring has a boat configuration. These two rings are located on nearly the same plane and the dihedral angles of these two least-squares planes are 18.2 (1)° for the non-disordered molecule, and 30.6 (1)° for the major component of the disordered molecule. There are two independent molecules in the asymmetric unit of the crystal. Atoms C3A and C4A of one of the molecules are disordered over two positions with a major component contribution of 71.5 (5)%. The two molecules have the same configuration and the absolute configurations of C2, C2A, C7 and C7A are S based on the results of anomalous dispersion. There are two intermolecular hydrogen bonds present between two independent molecules in the different asymmetric unit and connect them to form a pair of molecules (Table 1, Fig. 1 and Fig. 2).

Related literature top

For general background to secondary metabolites from B. thailandensis, see: Knappe et al. (2008); Nguyen et al. (2008); Seyedsayamdost et al. (2010); Ishida et al. (2010); Klausmeyer et al. (2011); Biggins et al. (2011); Wang et al. (2011, 2012); Ishida et al. (2012). For isolation of the title compound from other microorganisms, see: Chen (1960); Schmitz et al. (1983); Jayatilake et al. (1996); Ginz & Engelhardt (2000); Qi et al. (2009); Wang et al. (2010); Park et al. (2006). For the biological activity of the title compound, see: Holden et al. (1999); Fdhila et al. (2003). For large-scale genome sequencing, see: Mukhopadhyay et al. (2010); Yu et al. (2006); Zhuo et al. (2012). For our work on obtaining natural products from B. thailandensis MSMB43, see: Liu et al. (2012).

Experimental top

Isolation of the title compound Bacterial strain and culture conditions B. thailandensis strain MSMB43 was obtained from the US Centers for Disease Control (CDC) and was routinely activated on LB agar containing 50 mg ml-1 of apramycin (Am50) at 37°C for 1 to 2 days as a master plate. A single colony was then transferred into a 1-L flask containing 300 ml of LB medium and Am50, and the culture were growing at 37°C for 24 h as seed culture. For fed-batch fermentation 250 ml of seed culture was transferred into a 20-L fermentor (BioFlo IV, New Brunswick Scientific Co., USA) containing 12 L of M11 medium (10.0 g/L dextrose, 2.0 g/L pancreatic digest of casein, 1.0 g/L yeast extract, 1.0 g/L beef extract; pH 7.0). Fermentation was proceeded at 37°C, 300 rpm for 72 h, during which the pH was automatically adjusted by the fermentor with 1 N HCl or 1 N NaOH. Three liters of 10X M11 was fed to the fermentor from 24 h to 48 h at a flow rate of 0.125 ml/min.

Recovery of the crude extract

Bacterial cells and debris were removed by centrifugation of broth at 6,000 g for 15 min. Supernatant was applied to a 2-L column (Φ 8.0 x 40 cm) packed with a 50/50 mixture of Diaion HP-20 resin (Sigma-Aldrich, USA) and Amberlite XAD16 resin (Sigma-Aldrich) to allow absorption to occur. The resins were subsequently dried and extracted repeatedly with ethyl acetate. Organic extractions were pooled and dried in a rotary evaporator to yield a crude extract.

Isolation and purification of the title compound

Crude extract was mixed with 50 g silica gel (230–400 mesh, Whatman Purasil, USA). The mixture of silica gel was dried overnight and then applied to a 120 - g silica gel column, which has been equilibrated with hexane. The column was eluted sequentially with 1L of hexane (fraction 1), 1L of hexane:ethyl acetate (3:1, v/v) (fraction 2), 1L of hexane:ethyl acetate (1:1, v/v) (fraction 3), 1L of ethyl acetate (fraction 4), 1L of ethyl acetate:acetone (1:1, v/v) (fraction 5) and 2L of acetone (fraction 6). Fraction 5 was applied on a flash chromatography equipped with a silica gel Universal Column (Φ 23 ×123 mm, 16 g, Yamazen Corporation,) mounted atop an injection column (Φ 20 × 65 mm, 14 g, Yamazen Corporation). The column was eluted by mixtures of chloroform and acetone with increasing polarity according to the following scheme: 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 65%, 100% of acetone. Fraction eluted by 10% acetone was applied on a preparative HPLC system equipped with an Agilent Prep-C18 column (Φ 21.2 × 250 mm, 10 µm). The mobile phase consists of acetonitrile and water. The column was first eluted by 10% acetonitrile for 90 min, then by a gradient from 10% to 15% acetronitrile from 90 min to 100 min, then by 15% acetonitrile for 30 min, and finally by 100% acetonitrile for 20 min. The flow rate was 8 ml/min. The UV spectrum was monitored at 210 nm. The title compound was eluted at 30.0 min and other compounds were eluted at later times.

Crystallization

The purified title compound was dissolved in ethyl acetate and the crystals were obtained after a slow evaporation of the solvent at room temperature for 5 days.

Refinement top

All hydrogen atoms attached to the carbon atoms were placed in geometrically idealized positions (C—H = 0.98, 0.99 and 1.00 Å on the primary, secondary and tertiary aliphatic C atoms respectively). The H atoms were refined as riding, with isotropic displacement coefficients of Uiso(H) = 1.5Ueq(C) for methyl groups or 1.2Ueq(C) otherwise. The hydrogen atoms attached to N were located in the difference map and refined independently with restraints and constraints. The H atoms on the N were constrained to have the distances of 0.88 Å and the Uiso value were assigned as equal to 1.2 times the Ueq of the attached atoms.

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and OLEX2 (Dolomanov et al., 2009).

Figures top
[Figure 1] Fig. 1. A molecular structures of cyclo(-L-prolyl-L-valinyl-) in asymmetric unit with displacement ellipsoids shown at the 50% probability level. All hydrogen atoms attached to non-chiral carbon atoms and minor components of disordered atoms were omitted for clarity.
[Figure 2] Fig. 2. A packing diagram of cyclo(-L-prolyl-L-valinyl-), viewed along the b axis. For clarity, all H atoms attached to carbon atoms are omitted. The dashed lines represent hydrogen bonds.
(3S,8aS)-3-Isopropylhexahydropyrrolo[1,2-a]pyrazine-1,4- dione top
Crystal data top
C10H16N2O2F(000) = 848
Mr = 196.25Dx = 1.321 Mg m3
Orthorhombic, P212121Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2ac 2abCell parameters from 999 reflections
a = 5.6227 (1) Åθ = 2.6–69.5°
b = 10.2571 (2) ŵ = 0.76 mm1
c = 34.2115 (6) ÅT = 100 K
V = 1973.07 (6) Å3Needle, colourless
Z = 80.22 × 0.14 × 0.10 mm
Data collection top
Bruker APEXII area-detector
diffractometer
3668 independent reflections
Radiation source: fine-focus sealed tube3354 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.045
0.50° ω and 0.5 ° ϕ scansθmax = 69.5°, θmin = 2.6°
Absorption correction: multi-scan
(SADABS; Bruker, 2007)
h = 66
Tmin = 0.851, Tmax = 0.928k = 1212
28285 measured reflectionsl = 4041
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)] = 0.031H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.075 w = 1/[σ2(Fo2) + (0.0411P)2 + 0.438P]
where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max = 0.001
3668 reflectionsΔρmax = 0.30 e Å3
271 parametersΔρmin = 0.23 e Å3
3 restraintsAbsolute structure: Flack (1983), 1481 Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.05 (17)
Crystal data top
C10H16N2O2V = 1973.07 (6) Å3
Mr = 196.25Z = 8
Orthorhombic, P212121Cu Kα radiation
a = 5.6227 (1) ŵ = 0.76 mm1
b = 10.2571 (2) ÅT = 100 K
c = 34.2115 (6) Å0.22 × 0.14 × 0.10 mm
Data collection top
Bruker APEXII area-detector
diffractometer
3668 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2007)
3354 reflections with I > 2σ(I)
Tmin = 0.851, Tmax = 0.928Rint = 0.045
28285 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.031H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.075Δρmax = 0.30 e Å3
S = 1.02Δρmin = 0.23 e Å3
3668 reflectionsAbsolute structure: Flack (1983), 1481 Friedel pairs
271 parametersAbsolute structure parameter: 0.05 (17)
3 restraints
Special details top

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*/UeqOcc. (<1)
O10.0686 (2)0.57786 (10)0.42809 (3)0.0185 (2)
O20.6845 (2)0.29334 (10)0.46538 (3)0.0189 (2)
N10.1607 (2)0.39828 (12)0.41718 (4)0.0158 (3)
H10.120 (3)0.3984 (17)0.3926 (6)0.019*
N20.4056 (2)0.44278 (12)0.48284 (4)0.0151 (3)
C10.0698 (3)0.49203 (15)0.43957 (4)0.0154 (3)
C20.1570 (3)0.48683 (15)0.48164 (4)0.0152 (3)
H20.05590.42460.49680.018*
C30.1676 (3)0.61678 (15)0.50308 (5)0.0177 (3)
H3A0.01380.63730.51570.021*
H3B0.21090.68860.48510.021*
C40.3622 (3)0.59338 (16)0.53340 (4)0.0179 (3)
H4A0.42590.67670.54360.021*
H4B0.30250.54040.55550.021*
C50.5497 (3)0.51970 (15)0.51009 (4)0.0167 (3)
H5A0.65620.58040.49600.020*
H5B0.64630.46280.52720.020*
C60.4837 (3)0.34091 (14)0.46205 (4)0.0155 (3)
C70.2933 (3)0.28844 (14)0.43410 (4)0.0155 (3)
H70.17870.23600.45000.019*
C80.3954 (3)0.19864 (15)0.40270 (4)0.0175 (3)
H80.49580.13210.41630.021*
C90.1969 (3)0.12534 (16)0.38147 (5)0.0215 (3)
H9A0.10290.18700.36600.032*
H9B0.09400.08250.40070.032*
H9C0.26680.05960.36410.032*
C100.5556 (3)0.27055 (17)0.37385 (5)0.0218 (3)
H10A0.46030.33230.35860.033*
H10B0.63050.20750.35620.033*
H10C0.67900.31800.38820.033*
O1A1.0544 (2)0.43773 (11)0.33589 (3)0.0214 (2)
O2A0.4323 (2)0.77776 (12)0.27683 (3)0.0320 (3)
N1A0.7596 (2)0.58471 (13)0.34599 (4)0.0186 (3)
H1A0.799 (3)0.5861 (18)0.3720 (6)0.022*
N2A0.6766 (3)0.60603 (14)0.26780 (4)0.0221 (3)
C1A0.8856 (3)0.50385 (15)0.32357 (4)0.0172 (3)
C2A0.8103 (3)0.49229 (16)0.28135 (4)0.0190 (3)
H2A0.70140.41550.27950.023*0.715 (5)
H2B0.72740.40810.27560.023*0.285 (5)
C3A1.0062 (5)0.4726 (3)0.25090 (7)0.0201 (8)0.715 (5)
H3C0.97970.39060.23630.024*0.715 (5)
H3D1.16370.46800.26380.024*0.715 (5)
C4A0.9952 (6)0.5904 (3)0.22307 (7)0.0283 (7)0.715 (5)
H4C1.03890.56560.19600.034*0.715 (5)
H4D1.10010.66190.23200.034*0.715 (5)
C3B1.0460 (10)0.5041 (11)0.25504 (12)0.0201 (8)0.285 (5)
H3E1.15670.57260.26420.024*0.285 (5)
H3F1.13060.42010.25180.024*0.285 (5)
C4B0.9032 (14)0.5445 (9)0.21869 (9)0.0283 (7)0.285 (5)
H4E1.01310.58460.19960.034*0.285 (5)
H4F0.83550.46520.20650.034*0.285 (5)
C5A0.7235 (3)0.62958 (18)0.22612 (5)0.0281 (4)
H5C0.69820.72220.21910.034*0.715 (5)
H5D0.62280.57380.20930.034*0.715 (5)
H5E0.77430.72100.22200.034*0.285 (5)
H5F0.57900.61310.21040.034*0.285 (5)
C6A0.5464 (3)0.68536 (16)0.28998 (5)0.0218 (4)
C7A0.5431 (3)0.65377 (15)0.33383 (4)0.0187 (3)
H7A0.40410.59540.33900.022*
C8A0.5085 (3)0.77939 (15)0.35758 (4)0.0189 (3)
H8A0.37580.82890.34500.023*
C9A0.4322 (3)0.75127 (17)0.39963 (5)0.0234 (4)
H9D0.56010.70500.41330.035*
H9E0.28850.69720.39950.035*
H9F0.39900.83360.41310.035*
C10A0.7283 (3)0.86638 (17)0.35596 (5)0.0262 (4)
H10D0.69270.95040.36830.039*
H10E0.77400.88050.32860.039*
H10F0.85950.82410.36990.039*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0189 (5)0.0192 (5)0.0175 (5)0.0049 (5)0.0028 (5)0.0005 (4)
O20.0154 (5)0.0211 (5)0.0203 (5)0.0032 (5)0.0027 (5)0.0004 (5)
N10.0175 (7)0.0179 (6)0.0119 (6)0.0029 (6)0.0035 (5)0.0006 (5)
N20.0145 (6)0.0170 (6)0.0138 (6)0.0008 (5)0.0021 (5)0.0011 (5)
C10.0140 (7)0.0174 (7)0.0148 (7)0.0030 (7)0.0006 (6)0.0004 (6)
C20.0138 (7)0.0172 (7)0.0147 (7)0.0002 (6)0.0006 (6)0.0001 (6)
C30.0151 (7)0.0201 (7)0.0178 (7)0.0007 (6)0.0001 (6)0.0028 (6)
C40.0160 (8)0.0216 (7)0.0161 (7)0.0018 (7)0.0014 (6)0.0019 (6)
C50.0162 (7)0.0184 (7)0.0155 (7)0.0020 (7)0.0034 (6)0.0001 (6)
C60.0173 (8)0.0152 (7)0.0139 (7)0.0016 (6)0.0007 (6)0.0036 (6)
C70.0169 (8)0.0145 (7)0.0151 (7)0.0005 (6)0.0001 (6)0.0025 (6)
C80.0189 (8)0.0167 (7)0.0169 (7)0.0023 (6)0.0022 (6)0.0004 (6)
C90.0243 (8)0.0211 (8)0.0190 (8)0.0011 (7)0.0001 (7)0.0048 (7)
C100.0191 (8)0.0266 (8)0.0198 (8)0.0015 (7)0.0021 (7)0.0020 (7)
O1A0.0228 (6)0.0242 (6)0.0173 (5)0.0066 (5)0.0020 (5)0.0014 (5)
O2A0.0418 (7)0.0346 (7)0.0197 (6)0.0179 (6)0.0074 (6)0.0000 (5)
N1A0.0206 (7)0.0212 (7)0.0139 (6)0.0020 (6)0.0046 (5)0.0001 (6)
N2A0.0271 (7)0.0247 (7)0.0146 (6)0.0064 (6)0.0050 (6)0.0003 (5)
C1A0.0181 (8)0.0158 (7)0.0177 (7)0.0024 (6)0.0013 (6)0.0010 (6)
C2A0.0209 (8)0.0191 (7)0.0169 (8)0.0005 (7)0.0020 (7)0.0001 (7)
C3A0.0151 (12)0.0287 (18)0.0164 (9)0.0045 (11)0.0045 (9)0.0028 (9)
C4A0.0290 (18)0.0287 (16)0.0271 (11)0.0011 (12)0.0122 (11)0.0109 (11)
C3B0.0151 (12)0.0287 (18)0.0164 (9)0.0045 (11)0.0045 (9)0.0028 (9)
C4B0.0290 (18)0.0287 (16)0.0271 (11)0.0011 (12)0.0122 (11)0.0109 (11)
C5A0.0412 (11)0.0307 (9)0.0124 (8)0.0064 (8)0.0042 (7)0.0000 (7)
C6A0.0223 (9)0.0243 (8)0.0187 (8)0.0034 (8)0.0070 (7)0.0028 (7)
C7A0.0174 (8)0.0204 (8)0.0182 (7)0.0004 (6)0.0025 (7)0.0026 (6)
C8A0.0191 (8)0.0210 (8)0.0166 (7)0.0030 (7)0.0003 (6)0.0006 (6)
C9A0.0219 (8)0.0287 (9)0.0197 (8)0.0035 (7)0.0021 (7)0.0002 (7)
C10A0.0331 (10)0.0219 (8)0.0236 (8)0.0068 (8)0.0048 (8)0.0012 (7)
Geometric parameters (Å, º) top
O1—C11.2390 (19)N2A—C6A1.332 (2)
O2—C61.2354 (19)N2A—C2A1.463 (2)
N1—C11.331 (2)N2A—C5A1.470 (2)
N1—C71.4698 (19)C1A—C2A1.510 (2)
N1—H10.872 (19)C2A—C3A1.530 (3)
N2—C61.3381 (19)C2A—C3B1.607 (4)
N2—C51.4656 (19)C2A—H2A1.0000
N2—C21.469 (2)C2A—H2B1.0000
C1—C21.521 (2)C3A—C4A1.539 (3)
C2—C31.523 (2)C3A—H3C0.9900
C2—H21.0000C3A—H3D0.9900
C3—C41.527 (2)C4A—C5A1.583 (4)
C3—H3A0.9900C4A—H4C0.9900
C3—H3B0.9900C4A—H4D0.9900
C4—C51.523 (2)C3B—C4B1.537 (3)
C4—H4A0.9900C3B—H3E0.9900
C4—H4B0.9900C3B—H3F0.9900
C5—H5A0.9900C4B—C5A1.359 (7)
C5—H5B0.9900C4B—H4E0.9900
C6—C71.533 (2)C4B—H4F0.9900
C7—C81.527 (2)C5A—H5C0.9900
C7—H71.0000C5A—H5D0.9900
C8—C101.526 (2)C5A—H5E0.9900
C8—C91.529 (2)C5A—H5F0.9900
C8—H81.0000C6A—C7A1.535 (2)
C9—H9A0.9800C7A—C8A1.536 (2)
C9—H9B0.9800C7A—H7A1.0000
C9—H9C0.9800C8A—C10A1.525 (2)
C10—H10A0.9800C8A—C9A1.528 (2)
C10—H10B0.9800C8A—H8A1.0000
C10—H10C0.9800C9A—H9D0.9800
O1A—C1A1.2402 (19)C9A—H9E0.9800
O2A—C6A1.230 (2)C9A—H9F0.9800
N1A—C1A1.333 (2)C10A—H10D0.9800
N1A—C7A1.469 (2)C10A—H10E0.9800
N1A—H1A0.916 (19)C10A—H10F0.9800
C1—N1—C7121.45 (13)N2A—C2A—C3B100.7 (3)
C1—N1—H1116.9 (12)C1A—C2A—C3B107.4 (3)
C7—N1—H1121.0 (12)C3A—C2A—C3B15.0 (4)
C6—N2—C5125.23 (13)N2A—C2A—H2A107.1
C6—N2—C2122.52 (13)C1A—C2A—H2A107.1
C5—N2—C2112.22 (12)C3A—C2A—H2A107.1
O1—C1—N1124.88 (14)N2A—C2A—H2B112.8
O1—C1—C2121.83 (13)C1A—C2A—H2B112.7
N1—C1—C2113.28 (13)C3B—C2A—H2B109.8
N2—C2—C1110.11 (12)C2A—C3A—C4A106.77 (18)
N2—C2—C3102.62 (12)C2A—C3A—H3C110.4
C1—C2—C3115.95 (13)C4A—C3A—H3C110.4
N2—C2—H2109.3C2A—C3A—H3D110.4
C1—C2—H2109.3C4A—C3A—H3D110.4
C3—C2—H2109.3H3C—C3A—H3D108.6
C2—C3—C4102.58 (13)C3A—C4A—C5A101.4 (2)
C2—C3—H3A111.3C3A—C4A—H4C111.5
C4—C3—H3A111.3C5A—C4A—H4C111.5
C2—C3—H3B111.3C3A—C4A—H4D111.5
C4—C3—H3B111.3C5A—C4A—H4D111.5
H3A—C3—H3B109.2H4C—C4A—H4D109.3
C5—C4—C3102.61 (12)C4B—C3B—C2A92.4 (3)
C5—C4—H4A111.2C4B—C3B—H3E113.2
C3—C4—H4A111.2C2A—C3B—H3E113.2
C5—C4—H4B111.2C4B—C3B—H3F113.2
C3—C4—H4B111.2C2A—C3B—H3F113.2
H4A—C4—H4B109.2H3E—C3B—H3F110.6
N2—C5—C4102.57 (12)C5A—C4B—C3B114.2 (4)
N2—C5—H5A111.3C5A—C4B—H4E108.7
C4—C5—H5A111.3C3B—C4B—H4E108.7
N2—C5—H5B111.3C5A—C4B—H4F108.7
C4—C5—H5B111.3C3B—C4B—H4F108.7
H5A—C5—H5B109.2H4E—C4B—H4F107.6
O2—C6—N2124.02 (14)C4B—C5A—N2A102.1 (2)
O2—C6—C7123.85 (14)N2A—C5A—C4A101.27 (15)
N2—C6—C7112.11 (13)N2A—C5A—H5C111.5
N1—C7—C8112.07 (12)C4A—C5A—H5C111.5
N1—C7—C6109.31 (12)N2A—C5A—H5D111.5
C8—C7—C6112.84 (13)C4A—C5A—H5D111.5
N1—C7—H7107.5H5C—C5A—H5D109.3
C8—C7—H7107.5C4B—C5A—H5E111.5
C6—C7—H7107.5N2A—C5A—H5E110.3
C10—C8—C7112.67 (13)C4B—C5A—H5F113.5
C10—C8—C9111.19 (13)N2A—C5A—H5F110.7
C7—C8—C9110.87 (13)H5E—C5A—H5F108.7
C10—C8—H8107.3O2A—C6A—N2A123.30 (15)
C7—C8—H8107.3O2A—C6A—C7A120.94 (14)
C9—C8—H8107.3N2A—C6A—C7A115.76 (14)
C8—C9—H9A109.5N1A—C7A—C6A111.64 (13)
C8—C9—H9B109.5N1A—C7A—C8A111.08 (13)
H9A—C9—H9B109.5C6A—C7A—C8A109.98 (13)
C8—C9—H9C109.5N1A—C7A—H7A108.0
H9A—C9—H9C109.5C6A—C7A—H7A108.0
H9B—C9—H9C109.5C8A—C7A—H7A108.0
C8—C10—H10A109.5C10A—C8A—C9A111.84 (14)
C8—C10—H10B109.5C10A—C8A—C7A111.64 (13)
H10A—C10—H10B109.5C9A—C8A—C7A112.04 (13)
C8—C10—H10C109.5C10A—C8A—H8A107.0
H10A—C10—H10C109.5C9A—C8A—H8A107.0
H10B—C10—H10C109.5C7A—C8A—H8A107.0
C1A—N1A—C7A125.26 (13)C8A—C9A—H9D109.5
C1A—N1A—H1A116.0 (12)C8A—C9A—H9E109.5
C7A—N1A—H1A118.0 (12)H9D—C9A—H9E109.5
C6A—N2A—C2A126.07 (13)C8A—C9A—H9F109.5
C6A—N2A—C5A123.44 (14)H9D—C9A—H9F109.5
C2A—N2A—C5A110.25 (13)H9E—C9A—H9F109.5
O1A—C1A—N1A123.44 (14)C8A—C10A—H10D109.5
O1A—C1A—C2A119.79 (14)C8A—C10A—H10E109.5
N1A—C1A—C2A116.76 (13)H10D—C10A—H10E109.5
N2A—C2A—C1A112.62 (13)C8A—C10A—H10F109.5
N2A—C2A—C3A105.04 (15)H10D—C10A—H10F109.5
C1A—C2A—C3A117.37 (17)H10E—C10A—H10F109.5
C7—N1—C1—O1170.29 (14)C5A—N2A—C2A—C3A18.7 (2)
C7—N1—C1—C211.1 (2)C6A—N2A—C2A—C3B141.0 (4)
C6—N2—C2—C145.57 (18)C5A—N2A—C2A—C3B33.5 (4)
C5—N2—C2—C1136.54 (13)O1A—C1A—C2A—N2A158.55 (15)
C6—N2—C2—C3169.60 (13)N1A—C1A—C2A—N2A22.8 (2)
C5—N2—C2—C312.51 (15)O1A—C1A—C2A—C3A36.4 (2)
O1—C1—C2—N2143.76 (14)N1A—C1A—C2A—C3A145.00 (17)
N1—C1—C2—N234.95 (18)O1A—C1A—C2A—C3B48.6 (4)
O1—C1—C2—C327.8 (2)N1A—C1A—C2A—C3B132.8 (4)
N1—C1—C2—C3150.87 (14)N2A—C2A—C3A—C4A7.3 (3)
N2—C2—C3—C433.24 (14)C1A—C2A—C3A—C4A118.7 (3)
C1—C2—C3—C4153.30 (13)C2A—C3A—C4A—C5A27.8 (3)
C2—C3—C4—C542.04 (15)N2A—C2A—C3B—C4B40.4 (7)
C6—N2—C5—C4164.35 (13)C1A—C2A—C3B—C4B158.4 (5)
C2—N2—C5—C413.47 (16)C2A—C3B—C4B—C5A41.1 (9)
C3—C4—C5—N233.83 (15)C3B—C4B—C5A—N2A23.0 (8)
C5—N2—C6—O25.3 (2)C6A—N2A—C5A—C4B166.1 (4)
C2—N2—C6—O2172.35 (14)C2A—N2A—C5A—C4B8.6 (5)
C5—N2—C6—C7175.76 (13)C6A—N2A—C5A—C4A138.76 (19)
C2—N2—C6—C76.64 (19)C2A—N2A—C5A—C4A35.9 (2)
C1—N1—C7—C8175.93 (14)C3A—C4A—C5A—N2A37.7 (3)
C1—N1—C7—C650.06 (19)C2A—N2A—C6A—O2A177.98 (16)
O2—C6—C7—N1142.09 (14)C5A—N2A—C6A—O2A8.2 (3)
N2—C6—C7—N138.92 (17)C2A—N2A—C6A—C7A1.2 (2)
O2—C6—C7—C816.7 (2)C5A—N2A—C6A—C7A172.63 (15)
N2—C6—C7—C8164.34 (13)C1A—N1A—C7A—C6A31.1 (2)
N1—C7—C8—C1056.61 (17)C1A—N1A—C7A—C8A154.21 (15)
C6—C7—C8—C1067.31 (17)O2A—C6A—C7A—N1A154.28 (15)
N1—C7—C8—C968.72 (16)N2A—C6A—C7A—N1A26.5 (2)
C6—C7—C8—C9167.36 (13)O2A—C6A—C7A—C8A30.5 (2)
C7A—N1A—C1A—O1A172.92 (14)N2A—C6A—C7A—C8A150.31 (15)
C7A—N1A—C1A—C2A5.6 (2)N1A—C7A—C8A—C10A53.83 (17)
C6A—N2A—C2A—C1A26.9 (2)C6A—C7A—C8A—C10A70.28 (17)
C5A—N2A—C2A—C1A147.63 (14)N1A—C7A—C8A—C9A72.51 (17)
C6A—N2A—C2A—C3A155.8 (2)C6A—C7A—C8A—C9A163.39 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1Ai0.872 (19)2.016 (19)2.8734 (17)167.7 (17)
N1A—H1A···O1ii0.916 (19)2.06 (2)2.9710 (17)172.3 (17)
Symmetry codes: (i) x1, y, z; (ii) x+1, y, z.

Experimental details

Crystal data
Chemical formulaC10H16N2O2
Mr196.25
Crystal system, space groupOrthorhombic, P212121
Temperature (K)100
a, b, c (Å)5.6227 (1), 10.2571 (2), 34.2115 (6)
V3)1973.07 (6)
Z8
Radiation typeCu Kα
µ (mm1)0.76
Crystal size (mm)0.22 × 0.14 × 0.10
Data collection
DiffractometerBruker APEXII area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2007)
Tmin, Tmax0.851, 0.928
No. of measured, independent and
observed [I > 2σ(I)] reflections
28285, 3668, 3354
Rint0.045
(sin θ/λ)max1)0.608
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.031, 0.075, 1.02
No. of reflections3668
No. of parameters271
No. of restraints3
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.30, 0.23
Absolute structureFlack (1983), 1481 Friedel pairs
Absolute structure parameter0.05 (17)

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXTL (Sheldrick, 2008) and OLEX2 (Dolomanov et al., 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1Ai0.872 (19)2.016 (19)2.8734 (17)167.7 (17)
N1A—H1A···O1ii0.916 (19)2.06 (2)2.9710 (17)172.3 (17)
Symmetry codes: (i) x1, y, z; (ii) x+1, y, z.
 

Acknowledgements

Support for this work was obtained from a Research Growth Initiative Award from the University of Wisconsin–Milwaukee and NIH/NCI grant R01 CA 152212 (both to YQC). The authors thank Lara C. Spencer and Ilia A. Guzei (University of Wisconsin–Madison Department of Chemistry Crystallography Facility) for collecting the crystallographic data.

References

First citationBiggins, J. B., Gleber, C. D. & Brady, S. F. (2011). Org. Lett. 13, 1536–1539.  Web of Science CrossRef CAS PubMed
First citationBruker (2007). APEX2, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationChen, Y. S. (1960). Bull. Chem. Soc. Jpn, 24, 372–381.  CrossRef CAS
First citationDolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.  Web of Science CrossRef CAS IUCr Journals
First citationFdhila, F., Vazquez, V., Sanchez, J. L. & Riguera, R. (2003). J. Nat. Prod. 66, 1299–1301.  Web of Science CrossRef PubMed CAS
First citationFlack, H. D. (1983). Acta Cryst. A39, 876–881.  CrossRef CAS Web of Science IUCr Journals
First citationGinz, M. & Engelhardt, U. H. (2000). J. Agric. Food Chem. 48, 3528–3532.  Web of Science CrossRef PubMed CAS
First citationHolden, M. T., Ram Chhabra, S., de Nys, R., Stead, P., Bainton, N. J., Hill, P. J., Manefield, M., Kumar, N., Labatte, M., England, D., Rice, S., Givskov, M., Salmond, G. P., Stewart, G. S., Bycroft, B. W., Kjelleberg, S. & Williams, P. (1999). Mol. Microbiol. 33, 1254–1266.  Web of Science CrossRef PubMed CAS
First citationIshida, K., Lincke, T., Behnken, S. & Hertweck, C. (2010). J. Am. Chem. Soc. 132, 13966–13968.  Web of Science CrossRef CAS PubMed
First citationIshida, K., Lincke, T. & Hertweck, C. (2012). Angew. Chem. Int. Ed. Engl. 51, 5470–5474.  Web of Science CrossRef CAS PubMed
First citationJayatilake, G. S., Thornton, M. P., Leonard, A. C., Grimwade, J. E. & Baker, B. J. (1996). J. Nat. Prod. 59, 293–296.  CrossRef CAS PubMed Web of Science
First citationKlausmeyer, P., Shipley, S. M., Zuck, K. M. & McCloud, T. G. (2011). J. Nat. Prod. 74, 2039–2044.  Web of Science CrossRef CAS PubMed
First citationKnappe, T. A., Linne, U., Zirah, S., Rebuffat, S., Xie, X. & Marahiel, M. A. (2008). J. Am. Chem. Soc. 130, 11446–11454.  Web of Science CrossRef PubMed CAS
First citationLiu, X.-Y., Wang, C. & Cheng, Y.-Q. (2012). Acta Cryst. E68, o2757–o2758.  CSD CrossRef IUCr Journals
First citationMukhopadhyay, S., Thomason, M. K., Lentz, S., Nolan, N., Willner, K., Gee, J. E., Glass, M. B., Inglis, T. J., Merritt, A., Levy, A., Sozhamannan, S., Mateczun, A. & Read, T. D. (2010). J. Bacteriol. 192, 6313–6314.  Web of Science CrossRef CAS PubMed
First citationNguyen, T., Ishida, K., Jenke-Kodama, H., Dittmann, E., Gurgui, C., Hochmuth, T., Taudien, S., Platzer, M., Hertweck, C. & Piel, J. (2008). Nat. Biotechnol. 26, 225–233.  Web of Science CrossRef PubMed CAS
First citationPark, Y. C., Gunasekera, S. P., Lopez, J. V., McCarthy, P. J. & Wright, A. E. (2006). J. Nat. Prod. 69, 580–584.  Web of Science CSD CrossRef PubMed CAS
First citationQi, S. H., Xu, Y., Gao, J., Qian, P. Y. & Zhang, S. (2009). Anna. Microbiol. 59, 229–233.  CrossRef CAS
First citationSchmitz, F. J., Vanderah, D. J., Hollenbeak, K. H., Enwall, C. E. L. & Gopichand, Y. (1983). J. Org. Chem. 48, 3941–3945.
First citationSeyedsayamdost, M. R., Chandler, J. R., Blodgett, J. A., Lima, P. S., Duerkop, B. A., Oinuma, K., Greenberg, E. P. & Clardy, J. (2010). Org. Lett. 12, 716–719.  Web of Science CrossRef CAS PubMed
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationWang, C., Flemming, C. J. & Cheng, Y. Q. (2012). MedChemComm, 3, 976–981.  Web of Science CrossRef CAS PubMed
First citationWang, C., Henkes, L. M., Doughty, L. B., He, M., Wang, D., Meyer-Almes, F. J. & Cheng, Y. Q. (2011). J. Nat. Prod. 74, 2031–2038.  Web of Science CrossRef CAS PubMed
First citationWang, J. H., Quan, C. S., Qi, X. H., Li, X. & Fan, S. D. (2010). Ann. Microbiol. 396, 1773–1779.  CAS
First citationYu, Y., Kim, H. S., Chua, H. H., Lin, C. H., Sim, S. H., Lin, D., Derr, A., Engels, R., DeShazer, D., Birren, B., Nierman, W. C. & Tan, P. (2006). BMC Microbiol. 6, 46.
First citationZhuo, Y., Liu, L., Wang, Q., Liu, X., Ren, B., Liu, M., Ni, P., Cheng, Y. Q. & Zhang, L. (2012). J. Bacteriol. 194, 4749–4750.  Web of Science CrossRef CAS PubMed

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Volume 68| Part 11| November 2012| Pages o3182-o3183
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