research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 70| Part 12| December 2014| Pages 599-602
doi:10.1107/S1600536814025197

Crystal structure of N-(tert-but­­oxy­carbon­yl)phenyl­alanylde­hydro­alanine iso­propyl ester (Boc–Phe–ΔAla–OiPr)

Paweł Lenartowicz,a Maciej Makowski,a Bartosz Zarychtaa* and Krzysztof Ejsmonta

aFaculty of Chemistry, University of Opole, Oleska 48, 45-052 Opole, Poland
*Correspondence e-mail: bzarychta@uni.opole.pl

Edited by G. Smith, Queensland University of Technology, Australia (Received 3 November 2014; accepted 17 November 2014; online 29 November 2014)

In the title compound, the de­hydro­dipeptide (Boc–Phe–ΔAla–OiPr, C20H28N2O5), the mol­ecule has a trans conformation of the N-methyl­amide group. The geometry of the de­hydro­alanine moiety is to some extent different from those usually found in simple peptides, indicating conjugation between the H2C=C group and the peptide bond. The bond angles around de­hydro­alanine have unusually high values due to the steric hindrance, the same inter­action influencing the slight distortion from planarity of the de­hydro­alanine. The mol­ecule is stabilized by intra­molecular inter­actions between the isopropyl group and the N atoms of the peptide main chain. In the crystal, an N—H⋯O hydrogen bond links the mol­ecules into ribbons, giving a herringbone head-to-head packing arrangement extending along the [100] direction. In the stacks, the mol­ecules are linked by weak C—H⋯O hydrogen-bonding associations.

CCDC reference: 1034604

1. Chemical context

De­hydro­peptides are a class of compounds containing at least one residue of an α,β-de­hydro­amino acid. These compounds are of inter­est in many fields of science because of their structural and chemical properties. De­hydro­amino acids are found in natural products (Bonauer et al., 2006[Bonauer, C., Walenzyk, T. & König, B. (2006). Synthesis, pp. 1-20.]). One of the important classes of natural bacteriocins are lanti­biotics (e.g. nisin, subtilin), which are biosynthesized by Gram-positive bacteria. The unsaturated amino acid is introduced into the structure of these polycyclic peptides by post-translational modification of selected serine and threonine residues (Willey & van der Donk, 2007[Willey, J. M. & van der Donk, W. A. (2007). Annu. Rev. Microbiol. 61, 477-501.]). The development of synthetic methods for de­hydro­peptide preparation has resulted in a search for practical applications for these compounds. The de­hydro­amino acids are considered to be building blocks for the synthesis of new non-proteinogenic amino acids (Ferreira et al., 2010[Ferreira, P. M. T., Monteiro, L. S. & Pereira, G. (2010). Amino Acids, 39, 499-513.]). The double bond of the de­hydro­peptide can be used in different types of reaction, namely: addition of nucleophiles (Ferreira et al., 2001[Ferreira, P. M. T., Maia, H. L. S., Monteiro, L. S. & Sacramento, J. (2001). J. Chem. Soc. Perkin Trans. 1, pp. 3167-3173.]); alkyl­ation, providing α,α-disubstituted amino acids (Miyabe et al., 2005[Miyabe, H., Asada, R. & Takemoto, Y. (2005). Tetrahedron, 61, 385-393.]); Rh-catalysed conjugate addition of aryl­boronic acids providing β-aryl­alanine derivatives (Ferreira et al., 2013[Ferreira, P. M. T., Monteiro, L. S., Pereira, G., Castanheira, E. M. S. & Frost, C. G. (2013). Eur. J. Org. Chem. 3, 550-556.]); Cu-catalysed asymmetric hydro­boration as a step in the preparation of β-hy­droxy-α-amino acid derivatives being then used for the preparation of chiral drugs and bioactive mol­ecules (He et al., 2014[He, Z. T., Zhao, Y. S., Tian, P., Wang, C. C., Dong, H. Q. & Lin, G. Q. (2014). Org. Lett. 16, 1426-1429.]). Compounds containing de­hydro­amino acid residues also are considered to be inhibitors of enzymes (Makowski et al., 2001[Makowski, M., Pawełczak, M., Latajka, R., Nowak, K. & Kafarski, P. (2001). J. Pept. Sci. 7, 141-145.]; Latajka et al., 2006[Latajka, R., Makowski, M., Jewgiński, M., Pawełczak, M., Koroniak, H. & Kafarski, P. (2006). New J. Chem. 30, 1009-1018.], 2008[Latajka, R., Jewgiński, M., Makowski, M., Pawełczak, M., Huber, T., Sewald, N. & Kafarski, P. (2008). J. Pept. Sci. 14, 1084-1095.]). They are more resistant towards proteolytic enzymes than saturated analogues (English & Stammer, 1978[English, M. L. & Stammer, C. H. (1978). Biochem. Biophys. Res. Commun. 83, 1464-1467.]). The presence of sp2 hybridized carbon atoms in structures of de­hydro­peptides and the coupling of π-electrons between double and peptide bonds entail a number of structural consequences in the conformation of the peptides, and make them excellent subjects for conformational study (e.g. Jewgiński et al., 2014[Jewgiński, M., Krzciuk-Gula, J., Makowski, M., Latajka, R. & Kafarski, P. (2014). Beilstein J. Org. Chem. 10, 660-666.], 2013[Jewgiński, M., Latajka, R., Krezel, A., Haremza, K., Makowski, M. & Kafarski, P. (2013). J. Mol. Struct. 1035, 129-139.]; Demizu et al., 2010[Demizu, Y., Yamagata, N., Sato, Y., Doi, M., Tanaka, M., Okuda, H. & Kurihara, M. (2010). J. Pept. Sci. 16, 153-158.]; Lisowski et al., 2008[Lisowski, M., Latajka, R., Picur, B., Lis, T., Bryndal, I., Rospenk, M., Makowski, M. & Kafarski, P. (2008). Biopolymers, 89, 220-234.]). In this paper, the preparation of the title compound, N-(tert-but­oxy­carbon­yl)-phenyl­alanylde­hydro­alanine isopropyl ester and its structure determination by single-crystal X-ray crystallographic methods are presented.

[Scheme 1]

2. Structural commentary

The mol­ecular structure of N-(tert-but­oxy­carbon­yl)phenyl­alanylde­hydro­alanine isopropyl ester (Boc–Phe–ΔAla–OiPr, C20H28N2O5) is shown in Fig. 1[link]. The mol­ecule has a trans-conformation of the N-methyl­amide group. The geometry of the de­hydro­alanine is to some extent different from those usually found in simple peptides (Pauling, 1960[Pauling, L. (1960). The Nature of the Chemical Bond, p. 282. New York: Cornell University Press.]). In particular, the N19—C20 bond length is shorter while C17—N19 is longer [1.402 (3) Å and 1.354 (3) Å, respectively]. This is in excellent agreement with the values reported for N-acetyl­dehydro­alanine (Ajó et al., 1979[Ajó, D., Granozzi, G., Tondello, E., Del Pra, A. & Zanotti, G. (1979). J. Chem. Soc. Perkin Trans. 2, pp. 927-929.]), N-acetyl­bis-(de­hydro­phenyl­alanyl)glycine (Pieroni et al. 1975[Pieroni, O., Montagnoli, G., Fissi, A., Merlino, S. & Ciardelli, F. (1975). J. Am. Chem. Soc. 97, 6820-6826.]) and N-acetyl­ode­hydro­di­­meth­yl­amide (Rzeszotarska et al., 2002[Rzeszotarska, B., Siodłak, D., Broda, M. A., Dybała, I. & Kozioł, A. E. (2002). J. Pept. Res. 59, 79-89.]) and seems to be typical for α, β-unsaturated peptide systems (Jain & Chauhan, 1996[Jain, R. & Chauhan, V. S. (1996). Biopolymers, 40, 105-119.]). This indicates conjugation between the H2C=C group and the peptide bond. The valance angles around de­hydro­alanine have unusually large values [C21—C20—N19 = 126.9 (2), C17—N19—C20 = 126.8 (2) and O18—C17—N19 = 123.5 (2)°] due to the steric hindrance between atoms C21 and O18. The same inter­action influences the slight distortion from planarity of the de­hydro­alanine moiety. The ω, φ and ψ torsion angles (C9—C17—N19—C20, C17—N19—C20—C22 and N19—C20—C22—O24, respectively) of the de­hydro­alanine residue are −166.9 (2), 175.1 (2) and 178.0 (2)°. The geom­etries of the phenyl­aniline and the protecting groups are normal. There are four intra­molecular C—H⋯O close contacts but three of them have a D—H⋯A angle of less than 120°.

[Figure 1]
Figure 1
The mol­ecular structure of N-(tert-but­oxy­carbon­yl)phenyl­alanylde­hydro­alanine isopropyl ester (Boc–Phe–ΔAla–OiPr) showing 50% displacement ellipsoids. Intra­molecular C—H⋯O inter­actions are shown as dashed lines.

3. Supra­molecular features

In the crystal, strong inter­molecular N8—H⋯O7i hydrogen bonds (Table 1[link]) link the mol­ecules, giving a herringbone head-to-head packing arrangement, forming ribbons which extend along [100] (Fig. 2[link]). The ribbon structures are consolidated by weak intra-chain C—H⋯O hydrogen-bonding inter­actions.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N8—H8A⋯O7i 0.88 2.21 2.952 (2) 141
C3—H3C⋯O18ii 0.98 2.51 3.423 (3) 155
C21—H21A⋯O18 0.95 2.27 2.869 (3) 120
C26—H26B⋯O23i 0.98 2.52 3.462 (3) 162
Symmetry codes: (i) x-1, y, z; (ii) x+1, y-1, z.
[Figure 2]
Figure 2
The packing diagram of the title compound, viewed along the b axis, showing the inter­molecular hydrogen-bonding scheme (dashed lines).

4. Synthesis and crystallization

The de­hydro­dipeptide was obtained by condensation of N-protected phenyl­alanyl­amide with pyruvic acid in the presence of p-toluene­sulfonic acid (Makowski et al., 1985[Makowski, M., Rzeszotarska, B., Kubica, R. & Pietrzyńsi, G. (1985). Liebigs Ann. Chem. 5, 893-900.]). The esterification of the de­hydro­dipeptide was performed using the methodology described by Cossec et al. (2008[Cossec, B., Cosnier, F. & Burgart, M. (2008). Molecules, 13, 2394-2407.]). For this purpose 0.669 g (2 mM) of Boc–Phe–ΔAla was dissolved in 5 ml of methanol and calcium carbonate 0.329 g (1 mM) was added. The mixture was stirred for one h at room temperature, after which the solvent was evaporated. The residue was dissolved in 7 ml of DMF and isopropyl iodide (1.01 ml, 10 mM) was added in portions to the stirred mixture at room temperature during the reaction, the progress of which was monitored by thin-layer chromatography, using 5% methanol in chloro­form as eluent. After completion of the reaction, the solvent was evaporated and the oily residue was dissolved in ethyl acetate and washed consecutively with: 1 M HCl, saturated KHCO3, 0.1 M Na2S2O3 and brine. The organic layer was dried over anhydrous MgSO4 and the title compound was obtained in 81% yield (m.p. = 367–369 K). Recrystallization was performed using mixture of diethyl ether and hexane.

1H NMR (400 MHz, DMSO) δ 1.26 (d, J = 6.2 Hz, 6H, 2 × CH3Pri), 1.30 (s, 9H, CH3 t-Boc), 2.76 (dd, ABX system, J = 13.6, 10.8 Hz, 1H, CHAHB Phe), 3.02 (dd, ABX system, J = 13.6, 3.9 Hz, 1H, CHAHB Phe), 4.27–4.39 (m, 1H, CHPhe), 5.01 (hept, J = 6.2 Hz, 1H, CHPri), 5.70 (s, 1H, C=CHAHB), 6.23 (s, 1H, C=CHAHB), 7.15–7.36 (m, 6H, ArHPhe overlapped with NHPhe), δ 9.30 (s, 1H, NHΔAla). 13C NMR (101 MHz, DMSO) δ 21.43, 28.10, 36.63, 56.34, 69.40, 78.41, 108.65, 126.29, 128.07, 129.25, 132.71, 138.03, 155.53, 162.81, 171.53. IR (KBr, cm−1) 3600–2800 broad (H-bonding), 1715 (C=Oester), 1700 (C=Ourethane), 1690 IAB (C=Oamide), 1632 (C=C), 1526 IIAB (C–N and N–H), 1317 (CO–N–C=and N–(C=C)–CO), 1196 and 1166 (C–O–C), 896 (=CH2).

5. Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. All hydrogen atoms were positioned geometrically and treated as riding on their parent atoms with N—H = 0.88 Å and Uiso (H) = 1.2Ueq(N), C—Haromatic = 0.95 Å and Uiso (H) = 1.2Ueq(C), C—Hmeth­yl = 0.98 Å and Uiso (H) = 1.5Ueq(C); C—Hmethyl­ene = 0.99 Å or C—Hmethine = 0.95 Å and Uiso (H) = 1.2Ueq(C). Although not definitive, the absolute structure factor (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.]) with the C9(S) configuration, was −0.1 (6) for 1095 Friedel pairs.

Table 2
Experimental details

Crystal data
Chemical formula C20H28N2O5
Mr 376.44
Crystal system, space group Orthorhombic, P212121
Temperature (K) 100
a, b, c (Å) 5.2123 (2), 9.5031 (3), 41.3363 (17)
V (Å3) 2047.51 (13)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.09
Crystal size (mm) 0.33 × 0.18 × 0.14
 
Data collection
Diffractometer Oxford Diffraction Xcalibur CCD
No. of measured, independent and observed [I > 2σ(I)] reflections 14003, 4025, 3235
Rint 0.046
(sin θ/λ)max (Å−1) 0.617
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.046, 0.079, 0.98
No. of reflections 4025
No. of parameters 244
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.22, −0.22
Absolute structure Flack x determined using 1095 quotients [(I+)−(I−)]/[(I+)+(I−)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter −0.1 (6)
Computer programs: CrysAlis CCD and CrysAlis RED (Oxford Diffraction, 2008[Oxford Diffraction (2008). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd., Yarnton, England.]), SHELXL2014 and SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]).

Supporting information

CCDC reference: 1034604

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536814025197/zs2321sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536814025197/zs2321Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536814025197/zs2321Isup3.cml

checkCIF report


Chemical context top

De­hydro­peptides are a class of compounds containing at least one residue of an α,β-de­hydro­amino acid. These compounds are of inter­est in many fields of science because of their structural and chemical properties. De­hydro­amino acids are found in natural products (Bonauer et al., 2006). One of the important classes of natural bacteriocins are lanti­biotics (e.g. nisin, subtilin), which are biosynthesized by Gram-positive bacteria. The unsaturated amino acid is introduced into the structure of these polycyclic peptides by post-translational modification of selected serine and threonine residues (Willey & van der Donk, 2007). The development of synthetic methods for de­hydro­peptide preparation has resulted in a search for practical applications for these compounds. The de­hydro­amino acids are considered to be building blocks for the synthesis of new non-proteinogenic amino acids (Ferreira et al., 2010). The double bond of the de­hydro­peptide can be used in different types of reaction, namely: addition of nucleophiles (Ferreira et al., 2001); alkyl­ation, providing α,α-disubstituted amino acids (Miyabe et al., 2005); Rh-catalysed conjugate addition of aryl­boronic acids providing β-aryl­alanine derivatives (Ferreira et al., 2013); Cu-catalysed asymmetric hydro­boration as a step in the preparation of β-hy­droxy-α-amino acid derivatives being then used for the preparation of chiral drugs and bioactive molecules (He et al., 2014). Compounds containing de­hydro­amino acid residues also are considered to be inhibitors of enzymes (Makowski et al., 2001; Latajka et al., 2006, 2008). They are more resistant towards proteolytic enzymes than saturated analogues (English & Stammer, 1978). The presence of sp2 hybridized carbon atoms in structures of de­hydro­peptides and the coupling of π-electrons between double and peptide bonds entail a number of structural consequences in the conformation of the peptides, and make them excellent subjects for conformational study (e.g. Jewgiński et al., 2014, 2013; Demizu et al., 2010; Lisowski et al., 2008). In this paper, the preparation of the title compound, N-(tert-but­oxy­carbonyl)-phenyl­alanylde­hydro­alanine iso­propyl ester and its structure determination by single-crystal X-ray crystallographic methods are presented.

Structural commentary top

The molecular structure of N-(tert-but­oxy­carbonyl)­phenyl­alanylde­hydro­alanine iso­propyl ester (Boc–Phe–ΔAla–OiPr, C20H28N2O5) is shown in Fig. 1. The molecule has a trans-conformation of the N-methyl­amide group. The geometry of the de­hydro­alanine is to some extent different from those usually found in simple peptides (Pauling, 1960). In particular, the N19—C20 bond length is shorter while C17—N19 is longer [1.402 (3) Å and 1.354 (3) Å, respectively]. This is in excellent agreement with the values reported for N-acetyl­dehydro­alanine (Ajó et al., 1979), N-acetyl­bis-(de­hydro­phenyl­alany1)glycine (Pieroni et al. 1975) and N-acetyl­ode­hydro­dimethyl­amide (Rzeszotarska et al., 2002) and seems to be typical for α, β-unsaturated peptide systems (Jain & Chauhan, 1996). This indicates conjugation between the H2C═C group and the peptide bond. The valance angles around de­hydro­alanine have unusually large values [C21—C20—N19 = 126.9 (2), C17—N19—C20 = 126.8 (2) and O18—C17—N19 = 123.5 (2)°] due to the steric hindrance between atoms C21 and O18. The same inter­action influences the slight distortion from planarity of the de­hydro­alanine moiety. The ω, ϕ and ψ torsion angles (C9—C17—N19—C20, C17—N19—C20—C22 and N19—C20—C22—O24, respectively) of the de­hydro­alanine residue are -166.9 (2), 175.1 (2) and 178.0 (2)°. The geometries of the phenyl­aniline and the protecting groups are normal. There are four intra­molecular C—H···O inter­actions but three of them have a D—H···A angle of less than 120°.

Supra­molecular features top

In the crystal, strong inter­molecular N8—H···O7i hydrogen bonds (Table 1) link the molecules, giving a herringbone head-to-head packing arrangement, forming ribbons which extend along [100] (Fig. 2). The ribbon structures are stabilized by weak intra-chain C—H···O hydrogen-bonding inter­actions.

Synthesis and crystallization top

The de­hydro­dipeptide was obtained by condensation of N-protected phenyl­alanyl­amide with pyruvic acid in the presence of p-toluene­sulfonic acid (Makowski et al., 1985). The esterification of the de­hydro­dipeptide was performed using the methodology described by Cossec et al. (2008). For this purpose 0.669 g (2 mM) of Boc–Phe–ΔAla was dissolved in 5 ml of methanol and calcium carbonate 0.329 g (1 mM) was added. The mixture was stirred for one hour at room temperature, after which the solvent was evaporated. The residue was dissolved in 7 ml of DMF and iso­propyl iodide (1.01 ml, 10 mM) was added in portions to the stirred mixture at room temperature during the reaction, the progress of which was monitored by thin-layer chromatography, using 5% methanol in chloro­form as eluent. After completion of the reaction, the solvent was evaporated and the oily residue was dissolved in ethyl acetate and washed consecutively with: 1 M HCl, saturated KHCO3, 0.1 M Na2S2O3 and brine. The organic layer was dried over anhydrous MgSO4 and the title compound was obtained in 81% yield (m.p. = 367–369 K). Recrystallization was performed using mixture of di­ethyl ether and hexane.

1H NMR (400 MHz, DMSO) δ 1.26 (d, J = 6.2 Hz, 6H, 2 × CH3Pri), 1.30 (s, 9H, CH3 t-Boc), 2.76 (dd, ABX system, J = 13.6, 10.8 Hz, 1H, CHAHB Phe), 3.02 (dd, ABX system, J = 13.6, 3.9 Hz, 1H, CHAHB Phe), 4.27–4.39 (m, 1H, CHPhe), 5.01 (hept, J = 6.2 Hz, 1H, CHPri), 5.70 (s, 1H, C═ CHAHB), 6.23 (s, 1H, C═CHAHB), 7.15–7.36 (m, 6H, ArHPhe overlapped with NHPhe), δ 9.30 (s, 1H, NHΔAla). 13C NMR (101 MHz, DMSO) δ 21.43, 28.10, 36.63, 56.34, 69.40, 78.41, 108.65, 126.29, 128.07, 129.25, 132.71, 138.03, 155.53, 162.81, 171.53. IR (KBr, cm-1) 3600–2800 broad (H-bonding), 1715 (C═Oester), 1700 (C═Ourethane), 1690 IAB (C═Oamide), 1632 (C═C), 1526 IIAB (C–N and N–H), 1317 (CO–N–C═and N–(C═C)–CO), 1196 and 1166 (C–O–C), 896 (═CH2).

Refinement details top

Crystal data, data collection and structure refinement details are summarized in Table 2. All hydrogen atoms were positioned geometrically and treated as riding on their parent atoms with N—H = 0.88 Å and Uiso (H) = 1.2Ueq(N), C—Haromatic = 0.95 Å and Uiso (H) = 1.2Ueq(C), C—Hmethyl = 0.98 Å and Uiso (H) = 1.5Ueq(C); C—Hmethyl­ene = 0.99 Å or C—Hmethine = 0.95 Å and Uiso (H) = 1.2Ueq(C). Although not definitive, the absolute structure factor (Parsons et al., 2013) with the C9(S) configuration, was -0.1 (6) for 1095 Friedel pairs.

Related literature top

For related literature, see: Ajó et al. (1979); Bonauer et al. (2006); Cossec et al. (2008); Demizu et al. (2010); English & Stammer (1978); Ferreira et al. (2001, 2010, 2013); He et al. (2014); Jain & Chauhan (1996); Jewgiński et al. (2013, 2014); Latajka et al. (2006, 2008); Lisowski et al. (2008); Makowski et al. (1985, 2001); Miyabe et al. (2005); Pauling (1960); Pieroni et al. (1975); Rzeszotarska et al. (2002); Willey & van der Donk (2007).

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED (Oxford Diffraction, 2008); program(s) used to solve structure: SHELXL2014 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2008).

Figures top
Fig. 1. The molecular structure of N-(tert-butoxycarbonyl)phenylalanyldehydroalanine isopropyl ester (Boc–Phe–ΔAla–OiPr) showing 50% displacement ellipsoids. Intramolecular C—H···O interactions are shown as dashed lines.

Fig. 2. The packing diagram of the title compound, viewed along the b axis, showing the intermolecular hydrogen-bonding scheme (dashed lines).
N-(tert-Butoxycarbonyl)phenylalanyldehydroalanine isopropyl ester top
Crystal data top
C20H28N2O5Dx = 1.221 Mg m−3
Mr = 376.44Melting point = 367–369 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
a = 5.2123 (2) ÅCell parameters from 4025 reflections
b = 9.5031 (3) Åθ = 3.3–26.0°
c = 41.3363 (17) ŵ = 0.09 mm−1
V = 2047.51 (13) Å3T = 100 K
Z = 4Irregular, colourless
F(000) = 8080.33 × 0.18 × 0.14 mm
Data collection top
Oxford Diffraction Xcalibur CCD
diffractometer		3235 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.046
Graphite monochromatorθmax = 26.0°, θmin = 3.3°
ω scansh = −3→6
14003 measured reflectionsk = −11→11
4025 independent reflectionsl = −50→50
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.046 w = 1/[σ2(Fo2) + (0.0354P)2]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.079(Δ/σ)max < 0.001
S = 0.98Δρmax = 0.22 e Å−3
4025 reflectionsΔρmin = −0.22 e Å−3
244 parametersAbsolute structure: Flack x determined using 1095 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
0 restraintsAbsolute structure parameter: −0.1 (6)
Crystal data top
C20H28N2O5V = 2047.51 (13) Å3
Mr = 376.44Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 5.2123 (2) ŵ = 0.09 mm−1
b = 9.5031 (3) ÅT = 100 K
c = 41.3363 (17) Å0.33 × 0.18 × 0.14 mm
Data collection top
Oxford Diffraction Xcalibur CCD
diffractometer		3235 reflections with I > 2σ(I)
14003 measured reflectionsRint = 0.046
4025 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.046H-atom parameters constrained
wR(F2) = 0.079Δρmax = 0.22 e Å−3
S = 0.98Δρmin = −0.22 e Å−3
4025 reflectionsAbsolute structure: Flack x determined using 1095 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
244 parametersAbsolute structure parameter: −0.1 (6)
0 restraints
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C11.2709 (4)0.0969 (2)0.10948 (7)0.0184 (6)
C21.4195 (5)0.1063 (3)0.14083 (7)0.0249 (7)
H2A1.52040.19330.14110.037*
H2B1.53480.02520.14270.037*
H2C1.29950.10650.15910.037*
C31.1120 (5)−0.0366 (3)0.10835 (8)0.0325 (7)
H3A1.0176−0.04060.08790.049*
H3B0.9903−0.03690.12640.049*
H3C1.2254−0.11850.11000.049*
C41.4374 (5)0.1068 (3)0.07954 (7)0.0264 (7)
H4A1.53970.19320.08040.040*
H4B1.32820.10850.06020.040*
H4C1.55200.02520.07860.040*
O51.0713 (3)0.20736 (16)0.10856 (4)0.0194 (4)
C61.1322 (5)0.3446 (2)0.10987 (6)0.0151 (5)
O71.3475 (3)0.39442 (16)0.10970 (4)0.0188 (4)
N80.9116 (3)0.4203 (2)0.11214 (5)0.0148 (5)
H8A0.76750.37510.11600.018*
C90.9025 (4)0.5718 (2)0.10849 (6)0.0150 (5)
H9A1.07840.61050.11220.018*
C100.8141 (5)0.6145 (3)0.07443 (6)0.0176 (6)
H10A0.64020.57610.07070.021*
H10B0.80200.71840.07340.021*
C110.9882 (5)0.5648 (3)0.04781 (6)0.0167 (6)
C121.1944 (5)0.6462 (3)0.03752 (6)0.0231 (6)
H12A1.22810.73350.04790.028*
C131.3509 (5)0.6026 (3)0.01250 (7)0.0312 (7)
H13A1.48970.66010.00560.037*
C141.3057 (6)0.4757 (3)−0.00244 (7)0.0338 (8)
H14A1.41340.4455−0.01960.041*
C151.1046 (5)0.3924 (3)0.00748 (7)0.0317 (7)
H15A1.07390.3046−0.00280.038*
C160.9473 (5)0.4367 (3)0.03241 (6)0.0244 (7)
H16A0.80880.37870.03910.029*
C170.7185 (5)0.6377 (3)0.13324 (6)0.0177 (6)
O180.6189 (4)0.75177 (19)0.12844 (4)0.0266 (5)
N190.6785 (4)0.5605 (2)0.16029 (5)0.0168 (5)
H19A0.78410.48970.16360.020*
C200.4865 (4)0.5814 (3)0.18356 (6)0.0163 (6)
C210.3165 (5)0.6849 (3)0.18436 (6)0.0233 (6)
H21A0.31710.75490.16790.028*
H21B0.19400.68920.20130.028*
C220.4947 (5)0.4660 (3)0.20809 (6)0.0197 (6)
O230.6457 (4)0.36963 (19)0.20637 (4)0.0282 (5)
O240.3215 (3)0.48235 (17)0.23152 (4)0.0232 (4)
C250.3210 (5)0.3753 (3)0.25720 (6)0.0249 (6)
H25A0.50180.35200.26330.030*
C260.1889 (6)0.2446 (3)0.24504 (6)0.0274 (7)
H26A0.28490.20600.22670.041*
H26B0.01430.26820.23810.041*
H26C0.18140.17460.26240.041*
C270.1881 (6)0.4430 (3)0.28559 (6)0.0323 (7)
H27A0.28360.52690.29230.049*
H27B0.18070.37610.30360.049*
H27C0.01350.46990.27930.049*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0114 (11)0.0108 (13)0.0330 (15)0.0059 (10)−0.0014 (12)−0.0004 (12)
C20.0222 (14)0.0209 (15)0.0315 (16)0.0048 (13)0.0001 (13)0.0041 (13)
C30.0235 (14)0.0132 (13)0.061 (2)0.0028 (12)−0.0025 (16)0.0000 (14)
C40.0188 (14)0.0302 (17)0.0301 (16)0.0049 (14)−0.0019 (12)−0.0077 (14)
O50.0107 (9)0.0111 (9)0.0364 (11)0.0019 (7)0.0009 (9)−0.0001 (8)
C60.0163 (13)0.0113 (12)0.0177 (14)−0.0004 (11)−0.0003 (12)−0.0001 (11)
O70.0097 (8)0.0159 (9)0.0308 (10)−0.0025 (8)0.0001 (8)0.0022 (8)
N80.0084 (9)0.0100 (10)0.0261 (12)0.0007 (8)0.0041 (9)0.0023 (10)
C90.0126 (11)0.0106 (12)0.0218 (14)−0.0004 (10)0.0007 (11)0.0011 (12)
C100.0163 (12)0.0147 (13)0.0218 (14)0.0026 (12)−0.0026 (12)0.0014 (11)
C110.0146 (12)0.0189 (14)0.0167 (13)0.0044 (12)−0.0036 (11)0.0053 (12)
C120.0219 (14)0.0228 (15)0.0246 (15)0.0011 (14)−0.0054 (14)0.0055 (12)
C130.0203 (14)0.047 (2)0.0261 (16)0.0016 (16)0.0003 (14)0.0160 (15)
C140.0245 (15)0.056 (2)0.0208 (16)0.0117 (17)0.0058 (13)0.0011 (15)
C150.0312 (16)0.0375 (19)0.0265 (16)0.0061 (16)0.0001 (14)−0.0093 (14)
C160.0197 (14)0.0281 (16)0.0254 (16)−0.0011 (13)0.0002 (12)0.0002 (13)
C170.0154 (13)0.0148 (14)0.0228 (15)−0.0031 (12)−0.0022 (12)−0.0021 (12)
O180.0284 (11)0.0159 (10)0.0356 (12)0.0083 (9)0.0094 (9)0.0026 (9)
N190.0135 (10)0.0170 (11)0.0198 (12)0.0047 (10)0.0000 (9)0.0016 (10)
C200.0149 (12)0.0171 (14)0.0168 (13)−0.0033 (12)−0.0017 (11)−0.0029 (12)
C210.0232 (14)0.0245 (15)0.0221 (15)0.0037 (13)0.0067 (14)0.0011 (12)
C220.0165 (13)0.0235 (16)0.0193 (14)−0.0037 (12)−0.0031 (12)0.0003 (12)
O230.0242 (10)0.0282 (11)0.0322 (11)0.0096 (10)0.0027 (10)0.0085 (9)
O240.0231 (10)0.0256 (11)0.0207 (10)0.0009 (9)0.0058 (9)0.0035 (8)
C250.0228 (14)0.0280 (15)0.0238 (15)−0.0029 (15)0.0007 (13)0.0102 (13)
C260.0238 (15)0.0253 (15)0.0333 (16)0.0004 (14)0.0023 (14)0.0057 (13)
C270.0368 (17)0.0341 (18)0.0262 (16)−0.0036 (16)0.0039 (14)0.0025 (14)
Geometric parameters (Å, º) top
C1—O51.478 (3)C13—C141.375 (4)
C1—C21.513 (4)C13—H13A0.9500
C1—C41.514 (4)C14—C151.376 (4)
C1—C31.516 (3)C14—H14A0.9500
C2—H2A0.9800C15—C161.382 (4)
C2—H2B0.9800C15—H15A0.9500
C2—H2C0.9800C16—H16A0.9500
C3—H3A0.9800C17—O181.218 (3)
C3—H3B0.9800C17—N191.354 (3)
C3—H3C0.9800N19—C201.402 (3)
C4—H4A0.9800N19—H19A0.8800
C4—H4B0.9800C20—C211.324 (3)
C4—H4C0.9800C20—C221.494 (3)
O5—C61.343 (3)C21—H21A0.9500
C6—O71.218 (3)C21—H21B0.9500
C6—N81.360 (3)C22—O231.209 (3)
N8—C91.448 (3)C22—O241.333 (3)
N8—H8A0.8800O24—C251.470 (3)
C9—C101.536 (3)C25—C261.506 (4)
C9—C171.536 (3)C25—C271.507 (4)
C9—H9A1.0000C25—H25A1.0000
C10—C111.503 (3)C26—H26A0.9800
C10—H10A0.9900C26—H26B0.9800
C10—H10B0.9900C26—H26C0.9800
C11—C161.390 (4)C27—H27A0.9800
C11—C121.391 (3)C27—H27B0.9800
C12—C131.381 (4)C27—H27C0.9800
C12—H12A0.9500
O5—C1—C2109.9 (2)C11—C12—H12A119.4
O5—C1—C4109.7 (2)C14—C13—C12119.9 (3)
C2—C1—C4113.8 (2)C14—C13—H13A120.0
O5—C1—C3102.06 (17)C12—C13—H13A120.0
C2—C1—C3110.8 (2)C13—C14—C15120.1 (3)
C4—C1—C3109.9 (2)C13—C14—H14A120.0
C1—C2—H2A109.5C15—C14—H14A120.0
C1—C2—H2B109.5C14—C15—C16119.9 (3)
H2A—C2—H2B109.5C14—C15—H15A120.0
C1—C2—H2C109.5C16—C15—H15A120.0
H2A—C2—H2C109.5C15—C16—C11121.1 (3)
H2B—C2—H2C109.5C15—C16—H16A119.4
C1—C3—H3A109.5C11—C16—H16A119.4
C1—C3—H3B109.5O18—C17—N19123.5 (2)
H3A—C3—H3B109.5O18—C17—C9121.4 (2)
C1—C3—H3C109.5N19—C17—C9115.1 (2)
H3A—C3—H3C109.5C17—N19—C20126.8 (2)
H3B—C3—H3C109.5C17—N19—H19A116.6
C1—C4—H4A109.5C20—N19—H19A116.6
C1—C4—H4B109.5C21—C20—N19126.9 (2)
H4A—C4—H4B109.5C21—C20—C22123.2 (2)
C1—C4—H4C109.5N19—C20—C22109.9 (2)
H4A—C4—H4C109.5C20—C21—H21A120.0
H4B—C4—H4C109.5C20—C21—H21B120.0
C6—O5—C1121.48 (18)H21A—C21—H21B120.0
O7—C6—O5126.5 (2)O23—C22—O24124.9 (2)
O7—C6—N8125.0 (2)O23—C22—C20122.3 (2)
O5—C6—N8108.46 (19)O24—C22—C20112.8 (2)
C6—N8—C9123.12 (19)C22—O24—C25116.4 (2)
C6—N8—H8A118.4O24—C25—C26109.3 (2)
C9—N8—H8A118.4O24—C25—C27105.5 (2)
N8—C9—C10111.61 (19)C26—C25—C27113.7 (2)
N8—C9—C17110.89 (19)O24—C25—H25A109.4
C10—C9—C17108.39 (19)C26—C25—H25A109.4
N8—C9—H9A108.6C27—C25—H25A109.4
C10—C9—H9A108.6C25—C26—H26A109.5
C17—C9—H9A108.6C25—C26—H26B109.5
C11—C10—C9114.0 (2)H26A—C26—H26B109.5
C11—C10—H10A108.7C25—C26—H26C109.5
C9—C10—H10A108.7H26A—C26—H26C109.5
C11—C10—H10B108.7H26B—C26—H26C109.5
C9—C10—H10B108.7C25—C27—H27A109.5
H10A—C10—H10B107.6C25—C27—H27B109.5
C16—C11—C12117.8 (2)H27A—C27—H27B109.5
C16—C11—C10121.2 (2)C25—C27—H27C109.5
C12—C11—C10121.0 (2)H27A—C27—H27C109.5
C13—C12—C11121.2 (3)H27B—C27—H27C109.5
C13—C12—H12A119.4
C2—C1—O5—C660.9 (3)C12—C11—C16—C15−0.6 (4)
C4—C1—O5—C6−65.0 (3)C10—C11—C16—C15178.7 (2)
C3—C1—O5—C6178.5 (2)N8—C9—C17—O18−156.2 (2)
C1—O5—C6—O75.3 (4)C10—C9—C17—O18−33.4 (3)
C1—O5—C6—N8−173.4 (2)N8—C9—C17—N1924.2 (3)
O7—C6—N8—C912.2 (4)C10—C9—C17—N19147.0 (2)
O5—C6—N8—C9−169.1 (2)O18—C17—N19—C2013.5 (4)
C6—N8—C9—C1099.5 (3)C9—C17—N19—C20−166.9 (2)
C6—N8—C9—C17−139.5 (2)C17—N19—C20—C21−3.8 (4)
N8—C9—C10—C11−61.4 (3)C17—N19—C20—C22175.1 (2)
C17—C9—C10—C11176.2 (2)C21—C20—C22—O23177.4 (2)
C9—C10—C11—C1691.7 (3)N19—C20—C22—O23−1.5 (3)
C9—C10—C11—C12−89.0 (3)C21—C20—C22—O24−3.0 (3)
C16—C11—C12—C131.0 (4)N19—C20—C22—O24178.0 (2)
C10—C11—C12—C13−178.3 (2)O23—C22—O24—C251.1 (4)
C11—C12—C13—C14−0.7 (4)C20—C22—O24—C25−178.4 (2)
C12—C13—C14—C150.1 (4)C22—O24—C25—C26−78.0 (3)
C13—C14—C15—C160.3 (4)C22—O24—C25—C27159.4 (2)
C14—C15—C16—C110.0 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N8—H8A···O7i0.882.212.952 (2)141
C2—H2A···O70.982.483.049 (3)117
C3—H3C···O18ii0.982.513.423 (3)155
C4—H4A···O70.982.473.040 (3)116
C21—H21A···O180.952.272.869 (3)120
C26—H26A···O230.982.583.104 (3)114
C26—H26B···O23i0.982.523.462 (3)162
Symmetry codes: (i) x−1, y, z; (ii) x+1, y−1, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N8—H8A···O7i0.882.212.952 (2)141
C3—H3C···O18ii0.982.513.423 (3)155
C21—H21A···O180.952.272.869 (3)120
C26—H26B···O23i0.982.523.462 (3)162
Symmetry codes: (i) x−1, y, z; (ii) x+1, y−1, z.

Experimental details

Crystal data
Chemical formulaC20H28N2O5
Mr376.44
Crystal system, space groupOrthorhombic, P212121
Temperature (K)100
a, b, c (Å)5.2123 (2), 9.5031 (3), 41.3363 (17)
V (Å3)2047.51 (13)
Z4
Radiation typeMo Kα
µ (mm−1)0.09
Crystal size (mm)0.33 × 0.18 × 0.14
Data collection
DiffractometerOxford Diffraction Xcalibur CCD
diffractometer
Absorption correction–
No. of measured, independent and
observed [I > 2σ(I)] reflections		14003, 4025, 3235
Rint0.046
(sin θ/λ)max (Å−1)0.617
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.046, 0.079, 0.98
No. of reflections4025
No. of parameters244
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.22, −0.22
Absolute structureFlack x determined using 1095 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Absolute structure parameter−0.1 (6)

Computer programs: CrysAlis CCD (Oxford Diffraction, 2008), CrysAlis RED (Oxford Diffraction, 2008), SHELXL2014 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

 

Acknowledgements

These studies were supported by Wroclaw Research Centre EIT+ under the project `Biotechnologies and advanced medical technologies' – BioMed (POIG.01.01.02–02-003/08) financed from the European Regional Development Fund (Operational Programme Innovative Economy, 1.1.2). PL is the recipient of a PhD fellowship from a project funded by the European Social Foundation. MSc Błażej Dziuk is thanked for help with editing the manuscript.

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ISSN: 2056-9890
Volume 70| Part 12| December 2014| Pages 599-602
doi:10.1107/S1600536814025197
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