organic papers
Acta Cryst.(2006). E62, o2347–o2349 doi:10.1107/S1600536806017685 Okuet al. C
18H31Cl3N2O5
o2347
Acta Crystallographica Section EStructure Reports
Online
ISSN 1600-5368
tert
-Butoxycarbonyl-
L-leucyl-
L-valine
trichloroethyl ester (Boc-
L-Leu-
L-Val-OTce)
Hiroyuki Oku,* Teruya Endo, Keiichi Yamada and Ryoichi Katakai
Department of Chemistry, Gunma University, Kiryu, Gunma 376-8515, Japan
Correspondence e-mail: oku@chem.gunma-u.ac.jp
Key indicators
Single-crystal X-ray study
T= 173 K
Mean(C–C) = 0.007 A˚
Rfactor = 0.035
wRfactor = 0.087
Data-to-parameter ratio = 15.3
For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.
Received 2 May 2006 Accepted 12 May 2006
#2006 International Union of Crystallography
All rights reserved
The title compound, C18H31Cl3N2O5, an enantiopure
dipep-tide trichloroethyl ester, is one of two starting fragments in the synthesis of cyclosporin O analogs. In the crystal structure, molecules are linked by N—H O=C hydrogen bonds, forming a-spiral assembly along thecaxis.
Comment
Cyclosporins are naturally occurring physiologically active peptides containingN-methyl amino acid residues, which are potent chemotherapeutic agents (Humpherey & Chamberlin, 1997; Walgate, 1985; Stiller et al., 1984). The 2,2,2-trichloro-ethyl group (–OTce) is widely employed for carboxyl protection, and the compound (I) is one of two starting –OTce protected fragments in our synthetic study of cyclosporin O derivatives (Endoet al., 2003). We have recently reported the crystal structure of the other fragment, Boc-l-Leu-l -Ala-OTce (II) (Oku,et al., 2005). In this paper, we have studied the structure of (I) to assess the enantiopurity and crystallinity.
The molecular structure of (I) and the packing viewed along thecandaaxes are shown in Figs. 1, 2 and 3, respectively. The crystal structure of (I) is isostructural to that of (II) (space groupP65; Okuet al., 2005). The cell lengthsaandcare longer
than those of (II) by 0.140 (5) and 0.477 (13) A˚ , respectively. The main chain torsion angles of (I) deviate by only 2.0–5.3
Experimental
The title peptide, (I), was prepared by the coupling of Boc-Leu-OH -0.5H2O (4.5 g, 18 mmol) and HClVal-OTce (4.3 g, 15 mmol) in a solution-phase synthesis; yield 6.1 g (87%). Colorless needle crystals of (I) were grown by slow diffusion of hexane vapor into a solution in ethyl acetate. Analytical data (melting point,1H NMR, ESI–MS, and []D
20
) are in accordance with the expected structure; []D
20
=47.6
(c= 0.1, methanol), m.p. 377–379 K.
Crystal data
C18H31Cl3N2O5
Mr= 461.81 Hexagonal,P65
a= 12.245 (5) A˚ c= 27.416 (13) A˚ V= 3560 (3) A˚3
Z= 6
Dx= 1.292 Mg m
3 CuKradiation = 3.75 mm1
T= 173.1 K Needle, colorless 0.200.010.01 mm
Data collection
Rigaku R-AXIS RAPID diffractometer !scans
Absorption correction: none 32841 measured reflections
4352 independent reflections 1558 reflections withF2> 2(F2)
Rint= 0.068 max= 68.2
Refinement
Refinement onF2
R[F2> 2(F2)] = 0.035
wR(F2) = 0.087 S= 0.97 4352 reflections 285 parameters
All H-atom parameters refined
w= 4Fo2/[0.0002Fo2+ 0.2(Fo2) + 0.1]
(/)max< 0.001 max= 1.17 e A˚
3 min=0.93 e A˚
3
Absolute structure: Flack (1983), 2123 Friedel pairs
Flack parameter: 0.015 (15)
Table 1
Selected torsion angles ().
C32—O401—C41—C42 154.9 (4) C41—O401—C32—C31 179.8 (3) C15—N201—C21—C22 96.9 (4) C21—N201—C15—O101 178.5 (4)
C22—N301—C31—C32 63.9 (4) C31—N301—C22—C21 177.7 (3) N201—C21—C22—N301 128.6 (3) N301—C31—C32—O401 155.1 (3)
organic papers
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Okuet al. C [image:2.610.304.562.71.275.2]18H31Cl3N2O5 Acta Cryst.(2006). E62, o2347–o2349
Figure 1
A view of (I) with the atomic numbering scheme. Displacement ellipsoids are drawn at the 20% probability level.
Figure 2
[image:2.610.72.273.75.340.2]A packing diagram of (I), projected down thecaxis. H atoms have been omitted except for those of NH groups.
Figure 3
[image:2.610.332.536.314.597.2]Table 2
Hydrogen-bond geometry (A˚ ,).
D—H A D—H H A D A D—H A
N201—H201 O102i
0.95 1.98 2.902 (4) 162
N301—H301 O201ii
0.94 2.01 2.947 (4) 177
Symmetry codes: (i)xyþ1;x;z1
6; (ii)y;xþyþ1;zþ 1 6.
The ratio of observed/unique reflections was relatively low (36%), although the X-ray measurement was carried out at 173 K with Cu Kradiation. H atoms were positioned geometrically, with C—H and N—H = 0.95 A˚ , and refined using a riding model, with Uiso(H) assigned to be 1.2Ueq(carrier atom). The absolute configuration of (I) agrees with the fact that the1H NMR spectroscopic data detected no racemization in the preparation.
Data collection: RAPID-AUTO(Rigaku, 2003); cell refinement: RAPID-AUTO; data reduction: CrystalStructure (Rigaku, 2003); program(s) used to solve structure: SIR2002 (Burla et al., 2003); program(s) used to refine structure:CRYSTALS(Betteridgeet al., 2003); molecular graphics:ORTEP(Johnson, 1965); software used to prepare material for publication:CrystalStructure.
HO is grateful for a Grant-in-Aid for Scientific Research on Priority Areas (No. 14078101 and 16033211, Reaction Control of Dynamic Complexes) from the Ministry of Education Culture, Sports, Science and Technology, Japan.
References
Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003).J. Appl. Cryst.36, 1487.
Burla, M. C., Camalli, M., Carrozzini, B., Casarano, G. L., Giacovazzo, C., Polidori, G. & Spagna, R. (2003).J. Appl. Cryst.36, 1103.
Endo, T., Oku, H., Yamada, K. & Katakai, R. (2003).Peptide Science 2002, edited by T. Yamada, pp. 313–316. Osaka: The Japanese Peptide Society. Flack, H. D. (1983).Acta Cryst.A39, 876–881.
Humpherey, J. M. & Chamberlin, A. R. (1997).Chem. Rev.97, 2243–2266. Johnson, C. K. (1965).ORTEP. Oak Ridge National Laboratory, Oak Ridge,
Tennessee, USA.
Oku, H., Endo, T., Yamada, K. & Katakai, R. (2005).Acta Cryst.E61, o3864– o3866.
Rigaku (2003). CrystalStructureand RAPID-AUTO. Rigaku Corporation, Akishima, Tokyo, Japan.
Stiller, C. R., Dupre, J., Gent, M., Jenner, M. R., Keown, P. A., Laupacis, A., Martel, R., Rodger, N. W., von Graffenried, B. & Wolfe, B. M. (1984). Science,223, 1362–1367.
Walgate, R. (1985).Nature (London),318, 3.
organic papers
Acta Cryst.(2006). E62, o2347–o2349 Okuet al. C
supporting information
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Acta Cryst. (2006). E62, o2347–o2349
supporting information
Acta Cryst. (2006). E62, o2347–o2349 [https://doi.org/10.1107/S1600536806017685]
tert
-Butoxycarbonyl-
L-leucyl-
L-valine trichloroethyl ester (Boc-
L-Leu-
L-Val-OTce)
Hiroyuki Oku, Teruya Endo, Keiichi Yamada and Ryoichi Katakai
tert-Butoxycarbonyl-L-Leucyll-L-Valine Trichloroethyl Ester (Boc-L-Leu-L-Val-OTce)
Crystal data
C18H31Cl3N2O5 Mr = 461.81
Hexagonal, P65
Hall symbol: P 65 a = 12.245 (5) Å c = 27.416 (13) Å V = 3560 (3) Å3 Z = 6
F(000) = 1464.00
? # Insert any comments here.
Dx = 1.292 Mg m−3
Melting point = 377–379 K Cu Kα radiation, λ = 1.54187 Å Cell parameters from 30511 reflections θ = 4.2–62.2°
µ = 3.75 mm−1 T = 173 K Needle, colorless 0.20 × 0.01 × 0.01 mm
Data collection
Rigaku RAXIS-RAPID diffractometer
Detector resolution: 10.00 pixels mm-1 ω scans
32841 measured reflections 4352 independent reflections
1558 reflections with F2 > 2σ(F2) Rint = 0.068
θmax = 68.2° h = −14→14 k = −14→14 l = −32→32
Refinement
Refinement on F2 R[F2 > 2σ(F2)] = 0.035 wR(F2) = 0.087 S = 0.97 4352 reflections 285 parameters
All H-atom parameters refined
w = 4Fo2/[0.0002Fo2 + 0.2σ(Fo2) + 0.1]
(Δ/σ)max < 0.001
Δρmax = 1.17 e Å−3
Δρmin = −0.93 e Å−3
Absolute structure: Flack (1983), 2123 Friedel pairs
Absolute structure parameter: 0.015 (15)
Special details
Experimental. ? #Insert any special details here.
Refinement. Refinement using all reflections. The weighted R-factor (wR) and goodness of fit (S) are based on F2. R
-factor (gt) are based on F. The threshold expression of F2 > 2.0 σ(F2) is used only for calculating R-factor (gt).
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x y z Uiso*/Ueq
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Acta Cryst. (2006). E62, o2347–o2349
O101 1.1143 (2) 1.2369 (2) 0.87504 (9) 0.0424 (8) O102 1.0485 (2) 1.1818 (2) 0.95364 (10) 0.0553 (9) O201 0.8629 (2) 0.8101 (2) 0.88992 (9) 0.0453 (9) O301 0.6407 (2) 0.5842 (2) 0.95051 (12) 0.0569 (10) O401 0.7734 (2) 0.5107 (2) 0.94583 (11) 0.0587 (10) N201 0.9319 (2) 1.0687 (2) 0.88961 (11) 0.0360 (9) N301 0.8433 (3) 0.8209 (3) 0.97106 (11) 0.0365 (10) C11 1.2240 (4) 1.3582 (4) 0.88841 (17) 0.0483 (14) C12 1.1798 (4) 1.4409 (4) 0.9101 (2) 0.0814 (19) C13 1.2840 (4) 1.4074 (4) 0.83940 (18) 0.0781 (18) C14 1.3115 (4) 1.3405 (4) 0.92183 (17) 0.0790 (19) C15 1.0329 (3) 1.1647 (3) 0.91022 (16) 0.0378 (13) C21 0.8321 (3) 0.9759 (3) 0.91912 (12) 0.0369 (12) C22 0.8470 (3) 0.8621 (3) 0.92579 (14) 0.0333 (12) C23 0.7060 (3) 0.9347 (3) 0.89579 (13) 0.0412 (13) C24 0.5939 (4) 0.8571 (4) 0.92894 (17) 0.0529 (14) C25 0.5827 (4) 0.9388 (4) 0.96814 (16) 0.0679 (18) C26 0.4744 (4) 0.7954 (5) 0.8980 (2) 0.111 (2) C31 0.8525 (4) 0.7096 (4) 0.97878 (16) 0.0475 (15) C32 0.7423 (5) 0.5990 (4) 0.95651 (16) 0.0470 (15) C33 0.8691 (6) 0.6886 (5) 1.0327 (2) 0.103 (2) C34 0.9849 (5) 0.7957 (5) 1.0538 (2) 0.112 (2) C35 0.7698 (7) 0.6264 (7) 1.0607 (2) 0.193 (3) C41 0.6773 (4) 0.3997 (4) 0.92419 (18) 0.0642 (18) C42 0.7343 (4) 0.3390 (4) 0.89523 (18) 0.0587 (16)
H121 1.2489 1.5177 0.9191 0.090*
H122 1.1327 1.4542 0.8861 0.090*
H123 1.1299 1.4029 0.9380 0.090*
H131 1.3051 1.3516 0.8248 0.079*
H132 1.2273 1.4161 0.8190 0.079*
H133 1.3564 1.4856 0.8435 0.079*
H141 1.2731 1.3091 0.9525 0.083*
H142 1.3321 1.2842 0.9073 0.083*
H143 1.3845 1.4180 0.9265 0.082*
H201 0.9262 1.0614 0.8550 0.038*
H211 0.8349 1.0103 0.9504 0.041*
H231 0.7033 1.0063 0.8861 0.047*
H232 0.6987 0.8867 0.8678 0.047*
H241 0.6038 0.7943 0.9441 0.060*
H251 0.6554 0.9752 0.9875 0.082*
H252 0.5728 1.0018 0.9532 0.082*
H253 0.5132 0.8894 0.9882 0.082*
H261 0.4641 0.8579 0.8827 0.118*
H262 0.4813 0.7449 0.8737 0.118*
H263 0.4050 0.7463 0.9182 0.118*
H301 0.8357 0.8640 0.9982 0.041*
H311 0.9222 0.7209 0.9606 0.057*
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H341 1.0025 0.7757 1.0851 0.128*
H342 1.0539 0.8198 1.0329 0.128*
H343 0.9683 0.8617 1.0567 0.127*
H351 0.7422 0.6843 1.0642 0.170*
H352 0.7065 0.5530 1.0462 0.170*
H353 0.7894 0.6077 1.0920 0.170*
H411 0.6276 0.3446 0.9492 0.077*
H412 0.6274 0.4181 0.9036 0.077*
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
Cl401 0.1034 (11) 0.0575 (8) 0.0906 (10) 0.0371 (8) −0.0058 (9) −0.0151 (7) Cl402 0.0947 (10) 0.0741 (9) 0.0612 (7) 0.0470 (8) 0.0238 (7) 0.0145 (7) Cl403 0.1223 (13) 0.0673 (9) 0.0902 (10) 0.0568 (9) −0.0098 (9) 0.0100 (8) O101 0.0398 (17) 0.0307 (17) 0.0330 (15) −0.0003 (14) −0.0011 (14) −0.0010 (13) O102 0.056 (2) 0.052 (2) 0.0266 (17) 0.0036 (17) −0.0074 (14) −0.0023 (16) O201 0.068 (2) 0.0373 (17) 0.0338 (15) 0.0282 (16) 0.0124 (15) −0.0013 (14) O301 0.039 (2) 0.0407 (19) 0.081 (2) 0.0129 (17) 0.0064 (18) −0.0004 (16) O401 0.062 (2) 0.050 (2) 0.066 (2) 0.0284 (19) 0.0020 (17) −0.0130 (17) N201 0.043 (2) 0.0240 (18) 0.0272 (18) 0.0060 (17) 0.0028 (17) 0.0016 (15) N301 0.048 (2) 0.035 (2) 0.0215 (17) 0.0165 (18) 0.0056 (16) 0.0021 (16) C11 0.036 (2) 0.035 (2) 0.053 (3) 0.003 (2) −0.003 (2) 0.002 (2) C12 0.063 (3) 0.031 (2) 0.130 (5) 0.009 (2) 0.007 (3) −0.019 (3) C13 0.063 (3) 0.060 (3) 0.074 (3) 0.003 (3) 0.006 (3) 0.005 (2) C14 0.050 (3) 0.069 (3) 0.087 (4) 0.007 (2) −0.001 (3) −0.003 (3) C15 0.037 (2) 0.029 (2) 0.042 (2) 0.012 (2) 0.000 (2) 0.007 (2) C21 0.043 (2) 0.033 (2) 0.027 (2) 0.013 (2) 0.008 (2) −0.0028 (19) C22 0.034 (2) 0.026 (2) 0.033 (2) 0.010 (2) 0.011 (2) 0.001 (2) C23 0.041 (2) 0.033 (2) 0.043 (2) 0.013 (2) 0.006 (2) −0.001 (2) C24 0.045 (2) 0.037 (2) 0.068 (3) 0.015 (2) 0.013 (2) 0.008 (2) C25 0.066 (3) 0.071 (3) 0.067 (3) 0.034 (3) 0.022 (2) 0.004 (3) C26 0.044 (3) 0.129 (5) 0.121 (5) 0.014 (3) 0.009 (3) −0.008 (4) C31 0.047 (3) 0.045 (3) 0.050 (3) 0.023 (2) 0.007 (2) 0.013 (2) C32 0.050 (3) 0.042 (3) 0.044 (2) 0.019 (2) 0.012 (2) 0.011 (2) C33 0.109 (5) 0.057 (4) 0.080 (4) −0.004 (3) −0.034 (4) 0.027 (3) C34 0.129 (5) 0.063 (3) 0.127 (5) 0.035 (4) −0.067 (4) 0.006 (3) C35 0.200 (8) 0.170 (8) 0.054 (4) −0.024 (6) 0.010 (5) 0.019 (5) C41 0.076 (3) 0.048 (3) 0.068 (3) 0.030 (3) 0.009 (3) −0.014 (2) C42 0.076 (3) 0.047 (3) 0.050 (2) 0.029 (2) 0.010 (2) 0.006 (2)
Geometric parameters (Å, º)
Cl401—C42 1.773 (4) C12—H121 0.932
Cl402—C42 1.753 (4) C12—H122 0.940
Cl403—C42 1.744 (6) C12—H123 0.944
O101—C11 1.466 (4) C13—H131 0.934
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O102—C15 1.207 (5) C13—H133 0.931
O201—C22 1.239 (5) C14—H141 0.947
O301—C32 1.175 (7) C14—H142 0.934
O401—C32 1.346 (8) C14—H143 0.931
O401—C41 1.409 (4) C21—H211 0.947
N201—C15 1.332 (4) C23—H231 0.932
N201—C21 1.432 (4) C23—H232 0.944
N301—C22 1.332 (5) C24—H241 0.934
N301—C31 1.439 (7) C25—H251 0.937
C11—C12 1.489 (8) C25—H252 0.934
C11—C13 1.505 (6) C25—H253 0.937
C11—C14 1.506 (7) C26—H261 0.934
C21—C22 1.505 (7) C26—H262 0.941
C21—C23 1.506 (5) C26—H263 0.937
C23—C24 1.519 (5) C31—H311 0.936
C24—C25 1.520 (7) C33—H331 0.930
C24—C26 1.525 (6) C34—H341 0.948
C31—C32 1.483 (5) C34—H342 0.938
C31—C33 1.531 (7) C34—H343 0.930
C33—C34 1.485 (7) C35—H351 0.931
C33—C35 1.312 (9) C35—H352 0.934
C41—C42 1.480 (8) C35—H353 0.947
N201—H201 0.951 C41—H411 0.941
N301—H301 0.943 C41—H412 0.937
C11—O101—C15 119.1 (3) H132—C13—H133 109.5 C32—O401—C41 115.6 (4) C11—C14—H141 110.7 C15—N201—C21 120.5 (3) C11—C14—H142 108.7 C22—N301—C31 119.5 (3) C11—C14—H143 109.1 O101—C11—C12 109.2 (3) H141—C14—H142 110.0 O101—C11—C13 101.5 (3) H141—C14—H143 108.8 O101—C11—C14 111.3 (3) H142—C14—H143 109.5 C12—C11—C13 110.7 (4) N201—C21—H211 109.3
C12—C11—C14 112.5 (4) C22—C21—H211 107.9
C13—C11—C14 111.1 (4) C23—C21—H211 109.7
O101—C15—O102 126.1 (3) C21—C23—H231 108.5 O101—C15—N201 109.3 (3) C21—C23—H232 108.4 O102—C15—N201 124.6 (3) C24—C23—H231 108.2 N201—C21—C22 110.6 (3) C24—C23—H232 108.9 N201—C21—C23 110.6 (3) H231—C23—H232 108.5
C22—C21—C23 108.7 (3) C23—C24—H241 109.4
O201—C22—N301 122.0 (4) C25—C24—H241 108.6 O201—C22—C21 120.2 (3) C26—C24—H241 109.1 N301—C22—C21 117.8 (3) C24—C25—H251 109.7
C21—C23—C24 114.2 (3) C24—C25—H252 109.0
C23—C24—C25 111.2 (3) C24—C25—H253 110.0
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N301—C31—C32 109.7 (4) H252—C25—H253 109.9 N301—C31—C33 112.3 (4) C24—C26—H261 109.4
C32—C31—C33 112.4 (3) C24—C26—H262 109.9
O301—C32—O401 123.2 (3) C24—C26—H263 109.1 O301—C32—C31 127.5 (5) H261—C26—H262 108.3 O401—C32—C31 109.2 (5) H261—C26—H263 109.9 C31—C33—C34 112.1 (4) H262—C26—H263 110.2 C31—C33—C35) 120.1 (6) N301—C31—H311 106.2 C34—C33—C35) 118.9 (5) C32—C31—H311 105.2 O401—C41—C42 109.5 (4) C33—C31—H311 110.6 Cl401—C42—Cl402 108.8 (2) C31—C33—H331 101.1 Cl401—C42—Cl403 109.8 (2) C34—C33—H331 101.7 Cl401—C42—C41 106.8 (3) C35—C33—H331 97.4 Cl402—C42—Cl403 108.6 (2) C33—C34—H341 111.4 Cl402—C42—C41 111.0 (3) C33—C34—H342 110.7 Cl403—C42—C41 111.7 (3) C33—C34—H343 105.9
C15—N201—H201 119.8 H341—C34—H342 110.4
C21—N201—H201 119.7 H341—C34—H343 108.9
C22—N301—H301 121.2 H342—C34—H343 109.5
C31—N301—H301 119.4 C33—C35—H351 101.6
C11—C12—H121 109.7 C33—C35—H352 113.0
C11—C12—H122 107.6 C33—C35—H353 113.4
C11—C12—H123 110.7 H351—C35—H352 109.5
H121—C12—H122 109.7 H351—C35—H353 108.9
H121—C12—H123 108.6 H352—C35—H353 110.0
H122—C12—H123 110.5 O401—C41—H411 108.3
C11—C13—H131 110.4 O401—C41—H412 110.6
C11—C13—H132 109.7 C42—C41—H411 109.2
C11—C13—H133 109.1 C42—C41—H412 109.0
H131—C13—H132 108.6 H411—C41—H412 110.2
H131—C13—H133 109.5
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N201—C21—C22—O201 −51.1 (4) O401—C41—C42—Cl403 64.0 (4) N201—C21—C22—N301 128.6 (3)
Hydrogen-bond geometry (Å, º)
D—H···A D—H H···A D···A D—H···A
N201—H201···O102i 0.95 1.98 2.902 (4) 162
N301—H301···O201ii 0.94 2.01 2.947 (4) 177