organic compounds
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
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 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 In the crystal, two types of N—H⋯O hydrogen bonds link pairs of independent molecules.
Related literature
For general background to 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).
fromExperimental
Crystal data
|
Data collection: APEX2 (Bruker, 2007); cell SAINT (Bruker, 2007); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL and OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: SHELXTL and OLEX2.
Supporting information
10.1107/S1600536812043000/ff2084sup1.cif
contains datablocks global, I. DOI:Supporting information file. DOI: 10.1107/S1600536812043000/ff2084Isup2.cdx
Structure factors: contains datablock I. DOI: 10.1107/S1600536812043000/ff2084Isup3.hkl
Supporting information file. DOI: 10.1107/S1600536812043000/ff2084Isup4.cml
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
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). 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 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.
equipped with a silica gel Universal Column (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.
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.
Data collection: APEX2 (Bruker, 2007); cell
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).C10H16N2O2 | F(000) = 848 |
Mr = 196.25 | Dx = 1.321 Mg m−3 |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 999 reflections |
a = 5.6227 (1) Å | θ = 2.6–69.5° |
b = 10.2571 (2) Å | µ = 0.76 mm−1 |
c = 34.2115 (6) Å | T = 100 K |
V = 1973.07 (6) Å3 | Needle, colourless |
Z = 8 | 0.22 × 0.14 × 0.10 mm |
Bruker APEXII area-detector diffractometer | 3668 independent reflections |
Radiation source: fine-focus sealed tube | 3354 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.045 |
0.50° ω and 0.5 ° ϕ scans | θmax = 69.5°, θmin = 2.6° |
Absorption correction: multi-scan (SADABS; Bruker, 2007) | h = −6→6 |
Tmin = 0.851, Tmax = 0.928 | k = −12→12 |
28285 measured reflections | l = −40→41 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.031 | H 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 reflections | Δρmax = 0.30 e Å−3 |
271 parameters | Δρmin = −0.23 e Å−3 |
3 restraints | Absolute structure: Flack (1983), 1481 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.05 (17) |
C10H16N2O2 | V = 1973.07 (6) Å3 |
Mr = 196.25 | Z = 8 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 5.6227 (1) Å | µ = 0.76 mm−1 |
b = 10.2571 (2) Å | T = 100 K |
c = 34.2115 (6) Å | 0.22 × 0.14 × 0.10 mm |
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 = 0.928 | Rint = 0.045 |
28285 measured reflections |
R[F2 > 2σ(F2)] = 0.031 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.075 | Δρmax = 0.30 e Å−3 |
S = 1.02 | Δρmin = −0.23 e Å−3 |
3668 reflections | Absolute structure: Flack (1983), 1481 Friedel pairs |
271 parameters | Absolute structure parameter: 0.05 (17) |
3 restraints |
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. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
O1 | −0.0686 (2) | 0.57786 (10) | 0.42809 (3) | 0.0185 (2) | |
O2 | 0.6845 (2) | 0.29334 (10) | 0.46538 (3) | 0.0189 (2) | |
N1 | 0.1607 (2) | 0.39828 (12) | 0.41718 (4) | 0.0158 (3) | |
H1 | 0.120 (3) | 0.3984 (17) | 0.3926 (6) | 0.019* | |
N2 | 0.4056 (2) | 0.44278 (12) | 0.48284 (4) | 0.0151 (3) | |
C1 | 0.0698 (3) | 0.49203 (15) | 0.43957 (4) | 0.0154 (3) | |
C2 | 0.1570 (3) | 0.48683 (15) | 0.48164 (4) | 0.0152 (3) | |
H2 | 0.0559 | 0.4246 | 0.4968 | 0.018* | |
C3 | 0.1676 (3) | 0.61678 (15) | 0.50308 (5) | 0.0177 (3) | |
H3A | 0.0138 | 0.6373 | 0.5157 | 0.021* | |
H3B | 0.2109 | 0.6886 | 0.4851 | 0.021* | |
C4 | 0.3622 (3) | 0.59338 (16) | 0.53340 (4) | 0.0179 (3) | |
H4A | 0.4259 | 0.6767 | 0.5436 | 0.021* | |
H4B | 0.3025 | 0.5404 | 0.5555 | 0.021* | |
C5 | 0.5497 (3) | 0.51970 (15) | 0.51009 (4) | 0.0167 (3) | |
H5A | 0.6562 | 0.5804 | 0.4960 | 0.020* | |
H5B | 0.6463 | 0.4628 | 0.5272 | 0.020* | |
C6 | 0.4837 (3) | 0.34091 (14) | 0.46205 (4) | 0.0155 (3) | |
C7 | 0.2933 (3) | 0.28844 (14) | 0.43410 (4) | 0.0155 (3) | |
H7 | 0.1787 | 0.2360 | 0.4500 | 0.019* | |
C8 | 0.3954 (3) | 0.19864 (15) | 0.40270 (4) | 0.0175 (3) | |
H8 | 0.4958 | 0.1321 | 0.4163 | 0.021* | |
C9 | 0.1969 (3) | 0.12534 (16) | 0.38147 (5) | 0.0215 (3) | |
H9A | 0.1029 | 0.1870 | 0.3660 | 0.032* | |
H9B | 0.0940 | 0.0825 | 0.4007 | 0.032* | |
H9C | 0.2668 | 0.0596 | 0.3641 | 0.032* | |
C10 | 0.5556 (3) | 0.27055 (17) | 0.37385 (5) | 0.0218 (3) | |
H10A | 0.4603 | 0.3323 | 0.3586 | 0.033* | |
H10B | 0.6305 | 0.2075 | 0.3562 | 0.033* | |
H10C | 0.6790 | 0.3180 | 0.3882 | 0.033* | |
O1A | 1.0544 (2) | 0.43773 (11) | 0.33589 (3) | 0.0214 (2) | |
O2A | 0.4323 (2) | 0.77776 (12) | 0.27683 (3) | 0.0320 (3) | |
N1A | 0.7596 (2) | 0.58471 (13) | 0.34599 (4) | 0.0186 (3) | |
H1A | 0.799 (3) | 0.5861 (18) | 0.3720 (6) | 0.022* | |
N2A | 0.6766 (3) | 0.60603 (14) | 0.26780 (4) | 0.0221 (3) | |
C1A | 0.8856 (3) | 0.50385 (15) | 0.32357 (4) | 0.0172 (3) | |
C2A | 0.8103 (3) | 0.49229 (16) | 0.28135 (4) | 0.0190 (3) | |
H2A | 0.7014 | 0.4155 | 0.2795 | 0.023* | 0.715 (5) |
H2B | 0.7274 | 0.4081 | 0.2756 | 0.023* | 0.285 (5) |
C3A | 1.0062 (5) | 0.4726 (3) | 0.25090 (7) | 0.0201 (8) | 0.715 (5) |
H3C | 0.9797 | 0.3906 | 0.2363 | 0.024* | 0.715 (5) |
H3D | 1.1637 | 0.4680 | 0.2638 | 0.024* | 0.715 (5) |
C4A | 0.9952 (6) | 0.5904 (3) | 0.22307 (7) | 0.0283 (7) | 0.715 (5) |
H4C | 1.0389 | 0.5656 | 0.1960 | 0.034* | 0.715 (5) |
H4D | 1.1001 | 0.6619 | 0.2320 | 0.034* | 0.715 (5) |
C3B | 1.0460 (10) | 0.5041 (11) | 0.25504 (12) | 0.0201 (8) | 0.285 (5) |
H3E | 1.1567 | 0.5726 | 0.2642 | 0.024* | 0.285 (5) |
H3F | 1.1306 | 0.4201 | 0.2518 | 0.024* | 0.285 (5) |
C4B | 0.9032 (14) | 0.5445 (9) | 0.21869 (9) | 0.0283 (7) | 0.285 (5) |
H4E | 1.0131 | 0.5846 | 0.1996 | 0.034* | 0.285 (5) |
H4F | 0.8355 | 0.4652 | 0.2065 | 0.034* | 0.285 (5) |
C5A | 0.7235 (3) | 0.62958 (18) | 0.22612 (5) | 0.0281 (4) | |
H5C | 0.6982 | 0.7222 | 0.2191 | 0.034* | 0.715 (5) |
H5D | 0.6228 | 0.5738 | 0.2093 | 0.034* | 0.715 (5) |
H5E | 0.7743 | 0.7210 | 0.2220 | 0.034* | 0.285 (5) |
H5F | 0.5790 | 0.6131 | 0.2104 | 0.034* | 0.285 (5) |
C6A | 0.5464 (3) | 0.68536 (16) | 0.28998 (5) | 0.0218 (4) | |
C7A | 0.5431 (3) | 0.65377 (15) | 0.33383 (4) | 0.0187 (3) | |
H7A | 0.4041 | 0.5954 | 0.3390 | 0.022* | |
C8A | 0.5085 (3) | 0.77939 (15) | 0.35758 (4) | 0.0189 (3) | |
H8A | 0.3758 | 0.8289 | 0.3450 | 0.023* | |
C9A | 0.4322 (3) | 0.75127 (17) | 0.39963 (5) | 0.0234 (4) | |
H9D | 0.5601 | 0.7050 | 0.4133 | 0.035* | |
H9E | 0.2885 | 0.6972 | 0.3995 | 0.035* | |
H9F | 0.3990 | 0.8336 | 0.4131 | 0.035* | |
C10A | 0.7283 (3) | 0.86638 (17) | 0.35596 (5) | 0.0262 (4) | |
H10D | 0.6927 | 0.9504 | 0.3683 | 0.039* | |
H10E | 0.7740 | 0.8805 | 0.3286 | 0.039* | |
H10F | 0.8595 | 0.8241 | 0.3699 | 0.039* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0189 (5) | 0.0192 (5) | 0.0175 (5) | 0.0049 (5) | −0.0028 (5) | −0.0005 (4) |
O2 | 0.0154 (5) | 0.0211 (5) | 0.0203 (5) | 0.0032 (5) | −0.0027 (5) | −0.0004 (5) |
N1 | 0.0175 (7) | 0.0179 (6) | 0.0119 (6) | 0.0029 (6) | −0.0035 (5) | 0.0006 (5) |
N2 | 0.0145 (6) | 0.0170 (6) | 0.0138 (6) | 0.0008 (5) | −0.0021 (5) | −0.0011 (5) |
C1 | 0.0140 (7) | 0.0174 (7) | 0.0148 (7) | −0.0030 (7) | −0.0006 (6) | 0.0004 (6) |
C2 | 0.0138 (7) | 0.0172 (7) | 0.0147 (7) | 0.0002 (6) | 0.0006 (6) | 0.0001 (6) |
C3 | 0.0151 (7) | 0.0201 (7) | 0.0178 (7) | 0.0007 (6) | −0.0001 (6) | −0.0028 (6) |
C4 | 0.0160 (8) | 0.0216 (7) | 0.0161 (7) | −0.0018 (7) | −0.0014 (6) | −0.0019 (6) |
C5 | 0.0162 (7) | 0.0184 (7) | 0.0155 (7) | −0.0020 (7) | −0.0034 (6) | 0.0001 (6) |
C6 | 0.0173 (8) | 0.0152 (7) | 0.0139 (7) | −0.0016 (6) | −0.0007 (6) | 0.0036 (6) |
C7 | 0.0169 (8) | 0.0145 (7) | 0.0151 (7) | 0.0005 (6) | −0.0001 (6) | 0.0025 (6) |
C8 | 0.0189 (8) | 0.0167 (7) | 0.0169 (7) | 0.0023 (6) | −0.0022 (6) | −0.0004 (6) |
C9 | 0.0243 (8) | 0.0211 (8) | 0.0190 (8) | −0.0011 (7) | 0.0001 (7) | −0.0048 (7) |
C10 | 0.0191 (8) | 0.0266 (8) | 0.0198 (8) | 0.0015 (7) | 0.0021 (7) | −0.0020 (7) |
O1A | 0.0228 (6) | 0.0242 (6) | 0.0173 (5) | 0.0066 (5) | −0.0020 (5) | 0.0014 (5) |
O2A | 0.0418 (7) | 0.0346 (7) | 0.0197 (6) | 0.0179 (6) | −0.0074 (6) | 0.0000 (5) |
N1A | 0.0206 (7) | 0.0212 (7) | 0.0139 (6) | 0.0020 (6) | −0.0046 (5) | −0.0001 (6) |
N2A | 0.0271 (7) | 0.0247 (7) | 0.0146 (6) | 0.0064 (6) | −0.0050 (6) | −0.0003 (5) |
C1A | 0.0181 (8) | 0.0158 (7) | 0.0177 (7) | −0.0024 (6) | −0.0013 (6) | 0.0010 (6) |
C2A | 0.0209 (8) | 0.0191 (7) | 0.0169 (8) | 0.0005 (7) | −0.0020 (7) | 0.0001 (7) |
C3A | 0.0151 (12) | 0.0287 (18) | 0.0164 (9) | −0.0045 (11) | −0.0045 (9) | −0.0028 (9) |
C4A | 0.0290 (18) | 0.0287 (16) | 0.0271 (11) | 0.0011 (12) | 0.0122 (11) | 0.0109 (11) |
C3B | 0.0151 (12) | 0.0287 (18) | 0.0164 (9) | −0.0045 (11) | −0.0045 (9) | −0.0028 (9) |
C4B | 0.0290 (18) | 0.0287 (16) | 0.0271 (11) | 0.0011 (12) | 0.0122 (11) | 0.0109 (11) |
C5A | 0.0412 (11) | 0.0307 (9) | 0.0124 (8) | 0.0064 (8) | −0.0042 (7) | 0.0000 (7) |
C6A | 0.0223 (9) | 0.0243 (8) | 0.0187 (8) | 0.0034 (8) | −0.0070 (7) | −0.0028 (7) |
C7A | 0.0174 (8) | 0.0204 (8) | 0.0182 (7) | 0.0004 (6) | −0.0025 (7) | 0.0026 (6) |
C8A | 0.0191 (8) | 0.0210 (8) | 0.0166 (7) | 0.0030 (7) | −0.0003 (6) | 0.0006 (6) |
C9A | 0.0219 (8) | 0.0287 (9) | 0.0197 (8) | 0.0035 (7) | 0.0021 (7) | 0.0002 (7) |
C10A | 0.0331 (10) | 0.0219 (8) | 0.0236 (8) | −0.0068 (8) | 0.0048 (8) | −0.0012 (7) |
O1—C1 | 1.2390 (19) | N2A—C6A | 1.332 (2) |
O2—C6 | 1.2354 (19) | N2A—C2A | 1.463 (2) |
N1—C1 | 1.331 (2) | N2A—C5A | 1.470 (2) |
N1—C7 | 1.4698 (19) | C1A—C2A | 1.510 (2) |
N1—H1 | 0.872 (19) | C2A—C3A | 1.530 (3) |
N2—C6 | 1.3381 (19) | C2A—C3B | 1.607 (4) |
N2—C5 | 1.4656 (19) | C2A—H2A | 1.0000 |
N2—C2 | 1.469 (2) | C2A—H2B | 1.0000 |
C1—C2 | 1.521 (2) | C3A—C4A | 1.539 (3) |
C2—C3 | 1.523 (2) | C3A—H3C | 0.9900 |
C2—H2 | 1.0000 | C3A—H3D | 0.9900 |
C3—C4 | 1.527 (2) | C4A—C5A | 1.583 (4) |
C3—H3A | 0.9900 | C4A—H4C | 0.9900 |
C3—H3B | 0.9900 | C4A—H4D | 0.9900 |
C4—C5 | 1.523 (2) | C3B—C4B | 1.537 (3) |
C4—H4A | 0.9900 | C3B—H3E | 0.9900 |
C4—H4B | 0.9900 | C3B—H3F | 0.9900 |
C5—H5A | 0.9900 | C4B—C5A | 1.359 (7) |
C5—H5B | 0.9900 | C4B—H4E | 0.9900 |
C6—C7 | 1.533 (2) | C4B—H4F | 0.9900 |
C7—C8 | 1.527 (2) | C5A—H5C | 0.9900 |
C7—H7 | 1.0000 | C5A—H5D | 0.9900 |
C8—C10 | 1.526 (2) | C5A—H5E | 0.9900 |
C8—C9 | 1.529 (2) | C5A—H5F | 0.9900 |
C8—H8 | 1.0000 | C6A—C7A | 1.535 (2) |
C9—H9A | 0.9800 | C7A—C8A | 1.536 (2) |
C9—H9B | 0.9800 | C7A—H7A | 1.0000 |
C9—H9C | 0.9800 | C8A—C10A | 1.525 (2) |
C10—H10A | 0.9800 | C8A—C9A | 1.528 (2) |
C10—H10B | 0.9800 | C8A—H8A | 1.0000 |
C10—H10C | 0.9800 | C9A—H9D | 0.9800 |
O1A—C1A | 1.2402 (19) | C9A—H9E | 0.9800 |
O2A—C6A | 1.230 (2) | C9A—H9F | 0.9800 |
N1A—C1A | 1.333 (2) | C10A—H10D | 0.9800 |
N1A—C7A | 1.469 (2) | C10A—H10E | 0.9800 |
N1A—H1A | 0.916 (19) | C10A—H10F | 0.9800 |
C1—N1—C7 | 121.45 (13) | N2A—C2A—C3B | 100.7 (3) |
C1—N1—H1 | 116.9 (12) | C1A—C2A—C3B | 107.4 (3) |
C7—N1—H1 | 121.0 (12) | C3A—C2A—C3B | 15.0 (4) |
C6—N2—C5 | 125.23 (13) | N2A—C2A—H2A | 107.1 |
C6—N2—C2 | 122.52 (13) | C1A—C2A—H2A | 107.1 |
C5—N2—C2 | 112.22 (12) | C3A—C2A—H2A | 107.1 |
O1—C1—N1 | 124.88 (14) | N2A—C2A—H2B | 112.8 |
O1—C1—C2 | 121.83 (13) | C1A—C2A—H2B | 112.7 |
N1—C1—C2 | 113.28 (13) | C3B—C2A—H2B | 109.8 |
N2—C2—C1 | 110.11 (12) | C2A—C3A—C4A | 106.77 (18) |
N2—C2—C3 | 102.62 (12) | C2A—C3A—H3C | 110.4 |
C1—C2—C3 | 115.95 (13) | C4A—C3A—H3C | 110.4 |
N2—C2—H2 | 109.3 | C2A—C3A—H3D | 110.4 |
C1—C2—H2 | 109.3 | C4A—C3A—H3D | 110.4 |
C3—C2—H2 | 109.3 | H3C—C3A—H3D | 108.6 |
C2—C3—C4 | 102.58 (13) | C3A—C4A—C5A | 101.4 (2) |
C2—C3—H3A | 111.3 | C3A—C4A—H4C | 111.5 |
C4—C3—H3A | 111.3 | C5A—C4A—H4C | 111.5 |
C2—C3—H3B | 111.3 | C3A—C4A—H4D | 111.5 |
C4—C3—H3B | 111.3 | C5A—C4A—H4D | 111.5 |
H3A—C3—H3B | 109.2 | H4C—C4A—H4D | 109.3 |
C5—C4—C3 | 102.61 (12) | C4B—C3B—C2A | 92.4 (3) |
C5—C4—H4A | 111.2 | C4B—C3B—H3E | 113.2 |
C3—C4—H4A | 111.2 | C2A—C3B—H3E | 113.2 |
C5—C4—H4B | 111.2 | C4B—C3B—H3F | 113.2 |
C3—C4—H4B | 111.2 | C2A—C3B—H3F | 113.2 |
H4A—C4—H4B | 109.2 | H3E—C3B—H3F | 110.6 |
N2—C5—C4 | 102.57 (12) | C5A—C4B—C3B | 114.2 (4) |
N2—C5—H5A | 111.3 | C5A—C4B—H4E | 108.7 |
C4—C5—H5A | 111.3 | C3B—C4B—H4E | 108.7 |
N2—C5—H5B | 111.3 | C5A—C4B—H4F | 108.7 |
C4—C5—H5B | 111.3 | C3B—C4B—H4F | 108.7 |
H5A—C5—H5B | 109.2 | H4E—C4B—H4F | 107.6 |
O2—C6—N2 | 124.02 (14) | C4B—C5A—N2A | 102.1 (2) |
O2—C6—C7 | 123.85 (14) | N2A—C5A—C4A | 101.27 (15) |
N2—C6—C7 | 112.11 (13) | N2A—C5A—H5C | 111.5 |
N1—C7—C8 | 112.07 (12) | C4A—C5A—H5C | 111.5 |
N1—C7—C6 | 109.31 (12) | N2A—C5A—H5D | 111.5 |
C8—C7—C6 | 112.84 (13) | C4A—C5A—H5D | 111.5 |
N1—C7—H7 | 107.5 | H5C—C5A—H5D | 109.3 |
C8—C7—H7 | 107.5 | C4B—C5A—H5E | 111.5 |
C6—C7—H7 | 107.5 | N2A—C5A—H5E | 110.3 |
C10—C8—C7 | 112.67 (13) | C4B—C5A—H5F | 113.5 |
C10—C8—C9 | 111.19 (13) | N2A—C5A—H5F | 110.7 |
C7—C8—C9 | 110.87 (13) | H5E—C5A—H5F | 108.7 |
C10—C8—H8 | 107.3 | O2A—C6A—N2A | 123.30 (15) |
C7—C8—H8 | 107.3 | O2A—C6A—C7A | 120.94 (14) |
C9—C8—H8 | 107.3 | N2A—C6A—C7A | 115.76 (14) |
C8—C9—H9A | 109.5 | N1A—C7A—C6A | 111.64 (13) |
C8—C9—H9B | 109.5 | N1A—C7A—C8A | 111.08 (13) |
H9A—C9—H9B | 109.5 | C6A—C7A—C8A | 109.98 (13) |
C8—C9—H9C | 109.5 | N1A—C7A—H7A | 108.0 |
H9A—C9—H9C | 109.5 | C6A—C7A—H7A | 108.0 |
H9B—C9—H9C | 109.5 | C8A—C7A—H7A | 108.0 |
C8—C10—H10A | 109.5 | C10A—C8A—C9A | 111.84 (14) |
C8—C10—H10B | 109.5 | C10A—C8A—C7A | 111.64 (13) |
H10A—C10—H10B | 109.5 | C9A—C8A—C7A | 112.04 (13) |
C8—C10—H10C | 109.5 | C10A—C8A—H8A | 107.0 |
H10A—C10—H10C | 109.5 | C9A—C8A—H8A | 107.0 |
H10B—C10—H10C | 109.5 | C7A—C8A—H8A | 107.0 |
C1A—N1A—C7A | 125.26 (13) | C8A—C9A—H9D | 109.5 |
C1A—N1A—H1A | 116.0 (12) | C8A—C9A—H9E | 109.5 |
C7A—N1A—H1A | 118.0 (12) | H9D—C9A—H9E | 109.5 |
C6A—N2A—C2A | 126.07 (13) | C8A—C9A—H9F | 109.5 |
C6A—N2A—C5A | 123.44 (14) | H9D—C9A—H9F | 109.5 |
C2A—N2A—C5A | 110.25 (13) | H9E—C9A—H9F | 109.5 |
O1A—C1A—N1A | 123.44 (14) | C8A—C10A—H10D | 109.5 |
O1A—C1A—C2A | 119.79 (14) | C8A—C10A—H10E | 109.5 |
N1A—C1A—C2A | 116.76 (13) | H10D—C10A—H10E | 109.5 |
N2A—C2A—C1A | 112.62 (13) | C8A—C10A—H10F | 109.5 |
N2A—C2A—C3A | 105.04 (15) | H10D—C10A—H10F | 109.5 |
C1A—C2A—C3A | 117.37 (17) | H10E—C10A—H10F | 109.5 |
C7—N1—C1—O1 | −170.29 (14) | C5A—N2A—C2A—C3A | 18.7 (2) |
C7—N1—C1—C2 | 11.1 (2) | C6A—N2A—C2A—C3B | −141.0 (4) |
C6—N2—C2—C1 | −45.57 (18) | C5A—N2A—C2A—C3B | 33.5 (4) |
C5—N2—C2—C1 | 136.54 (13) | O1A—C1A—C2A—N2A | −158.55 (15) |
C6—N2—C2—C3 | −169.60 (13) | N1A—C1A—C2A—N2A | 22.8 (2) |
C5—N2—C2—C3 | 12.51 (15) | O1A—C1A—C2A—C3A | −36.4 (2) |
O1—C1—C2—N2 | −143.76 (14) | N1A—C1A—C2A—C3A | 145.00 (17) |
N1—C1—C2—N2 | 34.95 (18) | O1A—C1A—C2A—C3B | −48.6 (4) |
O1—C1—C2—C3 | −27.8 (2) | N1A—C1A—C2A—C3B | 132.8 (4) |
N1—C1—C2—C3 | 150.87 (14) | N2A—C2A—C3A—C4A | 7.3 (3) |
N2—C2—C3—C4 | −33.24 (14) | C1A—C2A—C3A—C4A | −118.7 (3) |
C1—C2—C3—C4 | −153.30 (13) | C2A—C3A—C4A—C5A | −27.8 (3) |
C2—C3—C4—C5 | 42.04 (15) | N2A—C2A—C3B—C4B | −40.4 (7) |
C6—N2—C5—C4 | −164.35 (13) | C1A—C2A—C3B—C4B | −158.4 (5) |
C2—N2—C5—C4 | 13.47 (16) | C2A—C3B—C4B—C5A | 41.1 (9) |
C3—C4—C5—N2 | −33.83 (15) | C3B—C4B—C5A—N2A | −23.0 (8) |
C5—N2—C6—O2 | 5.3 (2) | C6A—N2A—C5A—C4B | 166.1 (4) |
C2—N2—C6—O2 | −172.35 (14) | C2A—N2A—C5A—C4B | −8.6 (5) |
C5—N2—C6—C7 | −175.76 (13) | C6A—N2A—C5A—C4A | 138.76 (19) |
C2—N2—C6—C7 | 6.64 (19) | C2A—N2A—C5A—C4A | −35.9 (2) |
C1—N1—C7—C8 | −175.93 (14) | C3A—C4A—C5A—N2A | 37.7 (3) |
C1—N1—C7—C6 | −50.06 (19) | C2A—N2A—C6A—O2A | −177.98 (16) |
O2—C6—C7—N1 | −142.09 (14) | C5A—N2A—C6A—O2A | 8.2 (3) |
N2—C6—C7—N1 | 38.92 (17) | C2A—N2A—C6A—C7A | 1.2 (2) |
O2—C6—C7—C8 | −16.7 (2) | C5A—N2A—C6A—C7A | −172.63 (15) |
N2—C6—C7—C8 | 164.34 (13) | C1A—N1A—C7A—C6A | −31.1 (2) |
N1—C7—C8—C10 | 56.61 (17) | C1A—N1A—C7A—C8A | −154.21 (15) |
C6—C7—C8—C10 | −67.31 (17) | O2A—C6A—C7A—N1A | −154.28 (15) |
N1—C7—C8—C9 | −68.72 (16) | N2A—C6A—C7A—N1A | 26.5 (2) |
C6—C7—C8—C9 | 167.36 (13) | O2A—C6A—C7A—C8A | −30.5 (2) |
C7A—N1A—C1A—O1A | −172.92 (14) | N2A—C6A—C7A—C8A | 150.31 (15) |
C7A—N1A—C1A—C2A | 5.6 (2) | N1A—C7A—C8A—C10A | 53.83 (17) |
C6A—N2A—C2A—C1A | −26.9 (2) | C6A—C7A—C8A—C10A | −70.28 (17) |
C5A—N2A—C2A—C1A | 147.63 (14) | N1A—C7A—C8A—C9A | −72.51 (17) |
C6A—N2A—C2A—C3A | −155.8 (2) | C6A—C7A—C8A—C9A | 163.39 (14) |
D—H···A | D—H | H···A | D···A | 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. |
Experimental details
Crystal data | |
Chemical formula | C10H16N2O2 |
Mr | 196.25 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 100 |
a, b, c (Å) | 5.6227 (1), 10.2571 (2), 34.2115 (6) |
V (Å3) | 1973.07 (6) |
Z | 8 |
Radiation type | Cu Kα |
µ (mm−1) | 0.76 |
Crystal size (mm) | 0.22 × 0.14 × 0.10 |
Data collection | |
Diffractometer | Bruker APEXII area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Bruker, 2007) |
Tmin, Tmax | 0.851, 0.928 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 28285, 3668, 3354 |
Rint | 0.045 |
(sin θ/λ)max (Å−1) | 0.608 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.031, 0.075, 1.02 |
No. of reflections | 3668 |
No. of parameters | 271 |
No. of restraints | 3 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.30, −0.23 |
Absolute structure | Flack (1983), 1481 Friedel pairs |
Absolute structure parameter | 0.05 (17) |
Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXTL (Sheldrick, 2008) and OLEX2 (Dolomanov et al., 2009).
D—H···A | D—H | H···A | D···A | 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. |
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
Biggins, J. B., Gleber, C. D. & Brady, S. F. (2011). Org. Lett. 13, 1536–1539. Web of Science CrossRef CAS PubMed Google Scholar
Bruker (2007). APEX2, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Chen, Y. S. (1960). Bull. Chem. Soc. Jpn, 24, 372–381. CrossRef CAS Google Scholar
Dolomanov, 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 Google Scholar
Fdhila, F., Vazquez, V., Sanchez, J. L. & Riguera, R. (2003). J. Nat. Prod. 66, 1299–1301. Web of Science CrossRef PubMed CAS Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Ginz, M. & Engelhardt, U. H. (2000). J. Agric. Food Chem. 48, 3528–3532. Web of Science CrossRef PubMed CAS Google Scholar
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. Web of Science CrossRef PubMed CAS Google Scholar
Ishida, K., Lincke, T., Behnken, S. & Hertweck, C. (2010). J. Am. Chem. Soc. 132, 13966–13968. Web of Science CrossRef CAS PubMed Google Scholar
Ishida, K., Lincke, T. & Hertweck, C. (2012). Angew. Chem. Int. Ed. Engl. 51, 5470–5474. Web of Science CrossRef CAS PubMed Google Scholar
Jayatilake, 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 Google Scholar
Klausmeyer, P., Shipley, S. M., Zuck, K. M. & McCloud, T. G. (2011). J. Nat. Prod. 74, 2039–2044. Web of Science CrossRef CAS PubMed Google Scholar
Knappe, 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 Google Scholar
Liu, X.-Y., Wang, C. & Cheng, Y.-Q. (2012). Acta Cryst. E68, o2757–o2758. CSD CrossRef IUCr Journals Google Scholar
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. Web of Science CrossRef CAS PubMed Google Scholar
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. Web of Science CrossRef PubMed CAS Google Scholar
Park, 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 Google Scholar
Qi, S. H., Xu, Y., Gao, J., Qian, P. Y. & Zhang, S. (2009). Anna. Microbiol. 59, 229–233. CrossRef CAS Google Scholar
Schmitz, F. J., Vanderah, D. J., Hollenbeak, K. H., Enwall, C. E. L. & Gopichand, Y. (1983). J. Org. Chem. 48, 3941–3945. Google Scholar
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. Web of Science CrossRef CAS PubMed Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Wang, C., Flemming, C. J. & Cheng, Y. Q. (2012). MedChemComm, 3, 976–981. Web of Science CrossRef CAS PubMed Google Scholar
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. Web of Science CrossRef CAS PubMed Google Scholar
Wang, J. H., Quan, C. S., Qi, X. H., Li, X. & Fan, S. D. (2010). Ann. Microbiol. 396, 1773–1779. CAS Google Scholar
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. Google Scholar
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. Web of Science CrossRef CAS PubMed Google Scholar
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
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).