Acta Cryst.(2002). E58, o935±o936 DOI: 10.1107/S1600536802013259 Doi and Asano C36H60N4O12
o935
organic papers
Acta Crystallographica Section E Structure Reports
Online
ISSN 1600-5368
Montanastatin, cyclo[±(Val-
D-Hyv-
D-Val-Lac)
2±]
Mitsunobu Doi* and Akiko Asano
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
Correspondence e-mail: doit@gly.oups.ac.jp
Key indicators
Single-crystal X-ray study T= 100 K
Mean(C±C) = 0.003 AÊ Rfactor = 0.049 wRfactor = 0.111
Data-to-parameter ratio = 19.5
For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.
#2002 International Union of Crystallography Printed in Great Britain ± all rights reserved
Crystals of montanastatin anhydride, C36H60N4O12, were grown from a hexylene glycol solution. A crystallographic twofold axis runs through the centre of the molecule. The aliphatic side chains located on one side of the peptide ring form a hydrophobic region. The shape of the whole molecule is rectangular and is similar to the structure of the valinomycin analogue,viz.cyclo[±(d-Val-l-Hyv-l-Val-d-Hyv)2±].
Comment
Montanastatin has been isolated from a Montana soil actinomycete,Streptomyces anulatus, as a cancer-cell-growth inhibitory cyclooctadepsipeptide (Pettit et al., 1999). This peptide contains -hydroxyisovaleric acid (Hyv) and lactic acid (Lac), and is composed of two repeating units of tetra-peptide, Val-d-Hyv-d-Val-Lac. Such a repeated sequence is similar to that in valinomycin, which has three repeating units. Montanastatin gives some solvated crystals (refcode KAHMAH in the Cambridge Structural Database; Allen & Kennard, 1993). An anhydrous form, (I), was obtained from hexylene glycol solution, and its structure is reported here.
A crystallographic twofold axis is located in the montan-astatin molecule; the asymmetric unit is thus one half mole-cule. The backbone shape is a rectangular ring (Fig. 1a). The Lac residues shift from the peptide ring (Fig. 1b) making a small loop with an intramolecular hydrogen bond betweend -Val3and Lac4: N_3 O_4 (Table 1). The aliphatic side chains of Val1, d-Hyv2 and d-Val3 are located on one side of the peptide ring (Fig. 1b), forming a hydrophobic region. Only the methyl groups of Lac residues are located on the other side. In this structure, the chiral sequence of (lÐdÐdÐl) is impor-tant for creating a hydrophobic region. However, the relative positions of the side chains are different from those of vali-nomycin (Duaxet al., 1972; Karle, 1975). The conformational characteristics of montanastatin are similar to those of a valinomycin analogue, cyclo[±d-Val-l-Hyv-l-Val-d-Hyv)2±] (Grochulskiet al., 1992).
Experimental
Hyv was synthesized according to a previously reported method (Gisinet al., 1969), and montanastatin was synthsized by a conven-tional liquid-phase method. Montanastatin (20 mg) was dissolved in 0.2±0.3 ml hexylene glycol, and crystals grew after about 30 d at room temperature. A crystal was mounted on a nylon loop (Hampton Research Inc., USA) with glycerol and was ¯ash-frozen under a nitrogen stream at 100 K.
Crystal data
C36H60N4O12
Mr= 740.88 Orthorhombic,C2221
a= 13.488 (6) AÊ
b= 17.868 (7) AÊ
c= 16.452 (7) AÊ
V= 3965 (3) AÊ3
Z= 4
Dx= 1.241 Mg mÿ3
MoKradiation Cell parameters from 3994
re¯ections = 2.3±28.0 = 0.09 mmÿ1
T= 100 (2) K Block, colourless 0.320.240.20 mm
Data collection
Bruker SMART APEX CCD diffractometer
!scans
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)
Tmin= 0.854,Tmax= 0.982
13003 measured re¯ections
4717 independent re¯ections 4545 re¯ections withI> 2(I)
Rint= 0.031
max= 28.6
h=ÿ17!17
k=ÿ15!23
l=ÿ22!22
Re®nement
Re®nement onF2
R[F2> 2(F2)] = 0.049
wR(F2) = 0.111
S= 1.18 4717 re¯ections 242 parameters
H-atom parameters constrained
w= 1/[2(F
o2) + (0.0472P)2 + 1.956P]
whereP= (Fo2+ 2Fc2)/3 (/)max< 0.001
max= 0.32 e AÊÿ3
min=ÿ0.22 e AÊÿ3
Absolute structure: (Flack, 1983), 1912 Friedel pairs
Flack parameter = 0.1 (9)
Table 1
Hydrogen-bonding geometry (AÊ,).
DÐH A DÐH H A D A DÐH A
N_1ÐH5_1 O_2i 0.880 2.037 2.901 (2) 167.1
N_3ÐH22_3 O_4ii 0.880 2.363 3.037 (2) 133.6
Symmetry codes: (i)1
2x;32ÿy;2ÿz; (ii) 1ÿx;y;32ÿz.
The structure of montanastatin is consistent with the absolute con®gurations of the amino acids and carboxylic acids, Val,d-Val,
d-Hyv and Lac, although the Flack test results are meaningless. Data collection:SMART(Bruker, 1998); cell re®nement:SMART; data reduction:SAINT-Plus(Bruker, 1998); program(s) used to solve structure:SHELXS97 (Sheldrick, 1997); program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997); molecular graphics:
PLATON (Spek, 2001); software used to prepare material for publication:PARST(Nardelli, 1995).
References
Allen, F. H. & Kennard, O. (1993).Chem. Des. Autom. News,8, 1, 31±37. Bruker (1998).SAINT-Plus(Version 5) andSMART(Version 5). Bruker AXS
Inc., Madison, Wisconsin, USA.
Duax, W. L., Hauptman, H., Weeks, C. M. & Norton, D. A. (1972).Science,
176, 911±914.
Flack, H. D. (1983).Acta Cryst.A39, 876±881.
Gisin, B. F., Merri®eld, R. B. & Tosteson, D. C. (1969).J. Am. Chem. Soc.91, 2691±2695.
Grochulski, P., Smith, G. D., Langs, D. A., Duax, W. L., Pletnev, V. Z. & Ivanov, V. T. (1992).Biopolymers,32, 757±764.
Karle, I. L. (1975).J. Am. Chem. Soc.97, 4379±4386. Nardelli, M. (1995).J. Appl. Cryst.28, 659.
Pettit, G. R., Tan, R., Melody, N., Kielty, J. M., Pettit, R. K., Herald, D. L., Tucker, B. E., Mallavia, L. P., Doubek, D. L. & Schmidt, J. M. (1999).Bioorg. Med. Chem.7, 895±899.
Sheldrick, G. M. (1996).SADABS. University of GoÈttingen, Germany. Sheldrick, G. M. (1997). SHELXL97 and SHELXS97. University of
GoÈttingen, Germany.
Spek, A. L. (2001).PLATON.Utrecht University, The Netherlands. Figure 1
supporting information
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Acta Cryst. (2002). E58, o935–o936
supporting information
Acta Cryst. (2002). E58, o935–o936 [https://doi.org/10.1107/S1600536802013259]
Montanastatin, cyclo[
–
(Val-
D-Hyv-
D-Val-Lac)
2–
]
Mitsunobu Doi and Akiko Asano
Montanastatin: cyclo(–Val-D-Hyv-D-Val-Lac-)2, Hyv=alpha-hydroxyisovaleric acid, Lac=lactic acid
Crystal data
C36H60N4O12
Mr = 740.88
Orthorhombic, C2221
a = 13.488 (6) Å
b = 17.868 (7) Å
c = 16.452 (7) Å
V = 3965 (3) Å3
Z = 4
F(000) = 1600
Dx = 1.241 Mg m−3
Mo Kα radiation, λ = 0.71073 Å Cell parameters from 3994 reflections
θ = 2.3–28.0°
µ = 0.09 mm−1
T = 100 K Block, colourless 0.32 × 0.24 × 0.20 mm
Data collection
Bruker AXS SMART APEX CCD diffractometer
Radiation source: MacScience, M18XCE rotating anode
Graphite monochromator
Detector resolution: 8.366 pixels mm-1
ω scans
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)
Tmin = 0.854, Tmax = 0.982 13003 measured reflections 4717 independent reflections 4545 reflections with I > 2σ(I)
Rint = 0.031
θmax = 28.6°, θmin = 1.9°
h = −17→17
k = −15→23
l = −22→22
Refinement
Refinement on F2 Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.049
wR(F2) = 0.111
S = 1.18 4717 reflections 242 parameters 0 restraints
Primary atom site location: structure-invariant direct methods
Secondary atom site location: difference Fourier map
Hydrogen site location: inferred from neighbouring sites
H-atom parameters constrained
w = 1/[σ2(F
o2) + (0.0472P)2 + 1.956P] where P = (Fo2 + 2Fc2)/3
(Δ/σ)max < 0.001 Δρmax = 0.32 e Å−3 Δρmin = −0.22 e Å−3
Absolute structure: (Flack, 1983), 1912 Friedel pairs
Absolute structure parameter: 0.1 (9)
Special details
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)
x y z Uiso*/Ueq
ON_4 0.75840 (10) 0.75068 (8) 0.64983 (7) 0.0171 (3) CA_4 0.71119 (15) 0.77521 (11) 0.72391 (11) 0.0182 (4)
H1_4 0.7622 0.7910 0.7646 0.022*
CB_4 0.64520 (19) 0.84027 (12) 0.70235 (13) 0.0272 (5)
H2_4 0.5964 0.8244 0.6617 0.041*
H3_4 0.6855 0.8810 0.6801 0.041*
H4_4 0.6107 0.8578 0.7512 0.041*
C_4 0.65235 (13) 0.70761 (10) 0.75589 (11) 0.0139 (4) O_4 0.62526 (11) 0.65716 (8) 0.71054 (8) 0.0187 (3) N_1 0.63456 (12) 0.71050 (9) 0.83575 (9) 0.0145 (3)
H5_1 0.6545 0.7501 0.8630 0.017*
CA_1 0.58414 (13) 0.65153 (10) 0.87941 (10) 0.0125 (4)
H6_1 0.5427 0.6227 0.8399 0.015*
CB_1 0.65766 (14) 0.59673 (11) 0.92044 (12) 0.0158 (4)
H7_1 0.6186 0.5624 0.9563 0.019*
CG1_1 0.73278 (15) 0.63802 (13) 0.97357 (12) 0.0212 (4)
H8_1 0.7744 0.6701 0.9393 0.032*
H9_1 0.7746 0.6016 1.0020 0.032*
H10_1 0.6976 0.6689 1.0134 0.032*
CG2_1 0.71070 (16) 0.54893 (12) 0.85690 (13) 0.0228 (4)
H11_1 0.7527 0.5119 0.8843 0.034*
H12_1 0.7519 0.5811 0.8225 0.034*
H13_1 0.6615 0.5231 0.8232 0.034*
C_1 0.51590 (13) 0.68775 (11) 0.94122 (10) 0.0127 (4) O_1 0.51084 (11) 0.75341 (8) 0.95480 (8) 0.0192 (3) ON_2 0.46187 (9) 0.63488 (7) 0.97993 (7) 0.0130 (3) CA_2 0.40142 (13) 0.65922 (10) 1.04793 (10) 0.0129 (3)
H14_2 0.4171 0.7130 1.0587 0.015*
CB_2 0.43088 (14) 0.61425 (11) 1.12323 (11) 0.0149 (4)
H15_2 0.3845 0.6282 1.1681 0.018*
CG1_2 0.42158 (16) 0.53035 (11) 1.10937 (12) 0.0215 (4)
H16_2 0.4730 0.5139 1.0713 0.032*
H17_2 0.3561 0.5191 1.0867 0.032*
H18_2 0.4296 0.5040 1.1612 0.032*
CG2_2 0.53535 (15) 0.63533 (14) 1.14983 (12) 0.0258 (5)
H19_2 0.5371 0.6885 1.1645 0.039*
H20_2 0.5818 0.6261 1.1051 0.039*
H21_2 0.5544 0.6050 1.1970 0.039*
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Acta Cryst. (2002). E58, o935–o936
N_3 0.26771 (11) 0.63797 (9) 0.95056 (9) 0.0150 (3)
H22_3 0.3130 0.6197 0.9176 0.018*
CA_3 0.16727 (13) 0.65071 (11) 0.92056 (11) 0.0159 (4)
H23_3 0.1337 0.6850 0.9599 0.019*
CB_3 0.10523 (15) 0.57892 (12) 0.91610 (13) 0.0224 (4)
H24_3 0.1112 0.5540 0.9703 0.027*
CG1_3 0.14135 (18) 0.52245 (14) 0.85321 (15) 0.0321 (5)
H25_3 0.2139 0.5203 0.8543 0.048*
H26_3 0.1191 0.5378 0.7990 0.048*
H27_3 0.1142 0.4729 0.8659 0.048*
CG2_3 −0.00444 (18) 0.59678 (15) 0.90426 (16) 0.0347 (5)
H28_3 −0.0432 0.5505 0.9078 0.052*
H29_3 −0.0143 0.6197 0.8507 0.052*
H30_3 −0.0263 0.6316 0.9466 0.052*
C_3 0.82219 (14) 0.69313 (11) 0.65939 (12) 0.0172 (4) O_3 0.86226 (11) 0.67840 (9) 0.72215 (8) 0.0251 (3)
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
Geometric parameters (Å, º)
ON_4—C_3 1.350 (3) CA_2—C_2 1.518 (3)
ON_4—CA_4 1.443 (2) CA_2—CB_2 1.529 (3)
CA_4—CB_4 1.506 (3) CB_2—CG1_2 1.521 (3)
CA_4—C_4 1.538 (3) CB_2—CG2_2 1.523 (3)
C_4—O_4 1.226 (2) C_2—O_2 1.222 (2)
C_4—N_1 1.336 (2) C_2—N_3 1.342 (2)
N_1—CA_1 1.445 (2) N_3—CA_3 1.460 (2)
CA_1—C_1 1.517 (2) CA_3—C_3i 1.525 (3)
CA_1—CB_1 1.548 (3) CA_3—CB_3 1.533 (3)
CB_1—CG2_1 1.528 (3) CB_3—CG1_3 1.525 (3)
CB_1—CG1_1 1.528 (3) CB_3—CG2_3 1.526 (3)
C_1—O_1 1.196 (2) C_3—O_3 1.195 (2)
C_1—ON_2 1.353 (2) C_3—CA_3i 1.525 (3)
ON_2—CA_2 1.451 (2)
C_3—ON_4—CA_4 114.46 (15) ON_2—CA_2—CB_2 108.72 (15) ON_4—CA_4—CB_4 107.23 (16) C_2—CA_2—CB_2 113.31 (15) ON_4—CA_4—C_4 106.14 (15) CG1_2—CB_2—CG2_2 111.29 (17) CB_4—CA_4—C_4 112.43 (17) CG1_2—CB_2—CA_2 112.03 (16) O_4—C_4—N_1 124.97 (17) CG2_2—CB_2—CA_2 110.08 (16)
O_4—C_4—CA_4 121.54 (17) O_2—C_2—N_3 124.19 (17)
N_1—C_4—CA_4 113.49 (15) O_2—C_2—CA_2 118.62 (16)
C_4—N_1—CA_1 123.02 (15) N_3—C_2—CA_2 117.14 (15)
N_1—CA_1—C_1 107.92 (15) C_2—N_3—CA_3 120.84 (16)
N_1—CA_1—CB_1 112.11 (15) N_3—CA_3—C_3i 106.43 (15) C_1—CA_1—CB_1 111.49 (14) N_3—CA_3—CB_3 113.09 (16) CG2_1—CB_1—CG1_1 110.54 (17) C_3i—CA_3—CB_3 115.18 (16) CG2_1—CB_1—CA_1 110.80 (16) CG1_3—CB_3—CG2_3 111.19 (19) CG1_1—CB_1—CA_1 111.63 (16) CG1_3—CB_3—CA_3 114.31 (18) O_1—C_1—ON_2 124.50 (17) CG2_3—CB_3—CA_3 111.11 (18)
O_1—C_1—CA_1 125.34 (16) O_3—C_3—ON_4 123.83 (19)
ON_2—C_1—CA_1 110.16 (15) O_3—C_3—CA_3i 126.43 (19) C_1—ON_2—CA_2 117.15 (14) ON_4—C_3—CA_3i 109.73 (15) ON_2—CA_2—C_2 111.08 (14)
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Acta Cryst. (2002). E58, o935–o936
N_1—Ca_1—Cb_1—Cg1_1 53.0 (2) Ca_2—C_2—N_3—Ca_3 −163.8 (2) N_1—Ca_1—Cb_1—Cg2_1 −70.7 (2) O_2—C_2—N_3—Ca_3 13.8 (3) C_1—Ca_1—Cb_1—Cg1_1 −68.1 (2) C_2—N_3—Ca_3—Cb_3 −101.1 (2) C_1—Ca_1—Cb_1—Cg2_1 168.2 (2) N_3—Ca_3—Cb_3—Cg1_3 −66.7 (2) N_1—Ca_1—C_1—O_1 −4.9 (3) N_3—Ca_3—Cb_3—Cg2_3 166.5 (2) N_1—Ca_1—C_1—ON_2 175.8 (1) C_2—N_3—Ca_3—C_3i 131.6 (2) Cb_1—Ca_1—C_1—O_1 118.6 (2) N_3—Ca_3—C_3i—ON_4i −47.7 (2) Cb_1—Ca_1—C_1—On_2 −60.7 (2) Ca_3—C_3i—ON_4i—Ca_4i 155.7 (1) Ca_1—C_1—ON_2—Ca_2 172.8 (1)
Symmetry code: (i) −x+1, y, −z+3/2.
Hydrogen-bond geometry (Å, º)
D—H···A D—H H···A D···A D—H···A
N_1—H5_1···O_2ii 0.88 2.04 2.901 (2) 167
N_3—H22_3···O_4i 0.88 2.36 3.037 (2) 134
