Crystal structure of the tripeptide N-(benzyl-oxycarbon-yl)glycylglycyl-l-norvaline.

The title tripeptide, C17H23N3O6, contains a nonproteinogenic C-terminal amino acid residue, norvaline, which is an isomer of the amino acid valine. Norvaline, unlike valine, has an unbranched side chain. The mol-ecule has a Gly-Gly segment which adopts an extended conformation. The norvaline residue also adopts an extended backbone conformation while its side chain has a g (+) t conformation. In the crystal lattice, N-H⋯O and O-H⋯O hydrogen bonds stabilize the packing. Mol-ecules translated along the crystallographic a axis associate through an N-H⋯O hydrogen bond. The remaining three hydrogen bonds are between mol-ecules related by a 2 1 screw axis.

Related literature

For information on the amino acid norvaline, see: Kisumi, Sugiura & Chibata (1976 ▸); Kisumi, Sugiura, Kato & Chibata (1976 ▸); Alvarez-Carreño et al. (2013 ▸). For the conformation of glycine residues in proteins and peptides, see: Ramakrishnan & Srinivasan (1990 ▸). For examples of the conformational flexibility of Gly–Gly segments in peptides, see: Smith et al. (1978 ▸); Karle et al. (1983 ▸); Aubry et al. (1989 ▸).

Experimental

Crystal data

C17H23N3O6

M = 365.38

Orthorhombic,

a = 4.9857 (6) Å

b = 19.372 (2) Å

c = 19.476 (2) Å

V = 1881.1 (4) Å3

Z = 4

Mo Kα radiation

μ = 0.10 mm−1

T = 293 K

0.6 × 0.1 × 0.1 mm

Data collection

Bruker Kappa APEXII CCD diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2001 ▸) T min = 0.635, T max = 0.746

33216 measured reflections

2747 independent reflections

1421 reflections with I > 2σ(I)

R int = 0.156

Refinement

R[F 2 > 2σ(F 2)] = 0.083

wR(F 2) = 0.249

S = 1.05

2747 reflections

243 parameters

5 restraints

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.32 e Å−3

Δρmin = −0.23 e Å−3

Data collection: APEX2 (Bruker, 2007 ▸); cell refinement: SAINT-Plus (Bruker, 2007 ▸); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▸); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▸) and Mercury (Macrae et al., 2006 ▸); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S205698901500393X/rz5147sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S205698901500393X/rz5147Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901500393X/rz5147Isup3.docx

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901500393X/rz5147Isup4.cml

Click here for additional data file.

. DOI: 10.1107/S205698901500393X/rz5147fig1.tif

Thermal ellipsoid plot of the title compound drawn at the 50% probability level. Hydrogen atoms are omitted for clarity.

Click here for additional data file.

a . DOI: 10.1107/S205698901500393X/rz5147fig2.tif

Crystal packing of the title compound viewed down the a axis. Hydrogen bonds are represented as dotted lines. Hydrogen atoms, except those involved in hydrogen bonds, are omitted for clarity.

CCDC reference: 1051240

Additional supporting information: crystallographic information; 3D view; checkCIF report

C17H23N3O6	Z = 4
Mr = 365.38	F(000) = 776
Orthorhombic, P212121	Dx = 1.290 Mg m−3
Hall symbol: P 2ac 2ab	Mo Kα radiation, λ = 0.71073 Å
a = 4.9857 (6) Å	µ = 0.10 mm−1
b = 19.372 (2) Å	T = 293 K
c = 19.476 (2) Å	Needle-shaped, colourless
V = 1881.1 (4) Å3	0.6 × 0.1 × 0.1 mm

Bruker Kappa APEXII CCD diffractometer	2747 independent reflections
Radiation source: fine-focus sealed tube	1421 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.156
φ and ω scans	θmax = 28.4°, θmin = 1.5°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −5→6
Tmin = 0.635, Tmax = 0.746	k = −25→25
33216 measured reflections	l = −23→26

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.083	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.249	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ2(Fo2) + (0.1213P)2 + 0.3601P] where P = (Fo2 + 2Fc2)/3
2747 reflections	(Δ/σ)max < 0.001
243 parameters	Δρmax = 0.32 e Å−3
5 restraints	Δρmin = −0.23 e Å−3

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
C02	1.389 (2)	0.5256 (5)	0.1660 (5)	0.118 (3)
H02	1.4846	0.4846	0.1698	0.141*
C3B	0.793 (2)	−0.1324 (4)	0.1074 (5)	0.120 (3)
H3B1	0.7123	−0.1758	0.1212	0.144*
H3B2	0.6699	−0.1099	0.0759	0.144*
C06	1.051 (3)	0.5922 (5)	0.1164 (6)	0.161 (4)
H06	0.9095	0.5983	0.0860	0.194*
C3C	1.050 (3)	−0.1472 (6)	0.0703 (7)	0.177 (5)
H3C1	1.1610	−0.1754	0.1001	0.212*
H3C2	1.1434	−0.1037	0.0638	0.212*
C04	1.327 (5)	0.6385 (11)	0.2032 (8)	0.205 (11)
H04	1.3823	0.6749	0.2308	0.246*
C05	1.131 (5)	0.6467 (6)	0.1615 (11)	0.227 (10)
H05	1.0399	0.6885	0.1605	0.272*
C03	1.449 (4)	0.5791 (9)	0.2068 (6)	0.170 (6)
H03	1.5833	0.5736	0.2394	0.204*
C3D	1.033 (5)	−0.1837 (12)	−0.0004 (9)	0.326 (13)
H3D1	1.2106	−0.1923	−0.0174	0.489*
H3D2	0.9385	−0.1546	−0.0322	0.489*
H3D3	0.9389	−0.2266	0.0045	0.489*
H3	1.140 (14)	−0.013 (3)	0.156 (3)	0.082 (18)*
H3A	0.634 (15)	−0.076 (3)	0.184 (3)	0.085 (18)*
O3	1.2086 (8)	−0.1099 (2)	0.2416 (2)	0.0781 (11)
O2	0.5636 (8)	0.0281 (2)	0.1214 (2)	0.0778 (11)
N3	0.9505 (9)	−0.0208 (2)	0.1555 (3)	0.0688 (12)
C2A	0.9611 (10)	0.0969 (2)	0.1159 (3)	0.0652 (13)
H2A1	1.0607	0.1104	0.1565	0.078*
H2A2	1.0892	0.0875	0.0796	0.078*
N1	0.6659 (10)	0.3373 (2)	0.1138 (2)	0.0674 (11)
H1	0.5879	0.3575	0.1477	0.081*
C2'	0.8037 (10)	0.0320 (3)	0.1312 (3)	0.0593 (12)
O1	0.9811 (8)	0.23128 (19)	0.1640 (2)	0.0730 (10)
O08	0.9223 (10)	0.43006 (18)	0.1063 (2)	0.0864 (13)
C1'	0.8092 (10)	0.2157 (2)	0.1204 (3)	0.0586 (12)
O4	0.8419 (9)	−0.1744 (2)	0.2531 (3)	0.1091 (18)
H4	0.9301	−0.1940	0.2828	0.164*
O0	0.9319 (11)	0.3519 (2)	0.0213 (2)	0.0946 (15)
C1A	0.5999 (11)	0.2674 (2)	0.0977 (3)	0.0645 (13)
H1A1	0.5757	0.2635	0.0484	0.077*
H1A2	0.4304	0.2560	0.1193	0.077*
N2	0.7901 (9)	0.1528 (2)	0.0953 (2)	0.0652 (11)
H2	0.6687	0.1447	0.0650	0.078*
C3'	0.9838 (11)	−0.1230 (3)	0.2268 (3)	0.0727 (15)
C01	1.1876 (17)	0.5311 (3)	0.1188 (4)	0.092 (2)
C0'	0.8478 (13)	0.3711 (3)	0.0767 (3)	0.0683 (14)
C3A	0.8252 (14)	−0.0865 (3)	0.1714 (4)	0.0841 (17)
C07	1.1156 (18)	0.4727 (3)	0.0718 (4)	0.100 (2)
H07A	1.0404	0.4905	0.0294	0.120*
H07B	1.2742	0.4460	0.0607	0.120*

	U11	U22	U33	U12	U13	U23
C02	0.120 (6)	0.132 (7)	0.101 (6)	0.005 (6)	0.001 (6)	0.002 (5)
C3B	0.131 (6)	0.083 (4)	0.145 (6)	−0.026 (4)	−0.064 (5)	0.029 (4)
C06	0.163 (9)	0.094 (6)	0.228 (12)	0.020 (7)	0.003 (11)	0.006 (7)
C3C	0.150 (8)	0.165 (9)	0.215 (11)	0.058 (8)	−0.072 (7)	−0.103 (9)
C04	0.26 (2)	0.206 (18)	0.151 (12)	−0.117 (19)	0.104 (14)	−0.084 (13)
C05	0.26 (2)	0.080 (7)	0.34 (3)	−0.005 (11)	0.09 (2)	−0.068 (11)
C03	0.191 (13)	0.209 (14)	0.110 (8)	−0.065 (13)	0.013 (8)	−0.043 (9)
C3D	0.30 (2)	0.42 (3)	0.255 (19)	0.06 (3)	−0.050 (19)	−0.17 (2)
O3	0.062 (2)	0.103 (3)	0.069 (2)	0.005 (2)	0.0027 (19)	0.023 (2)
O2	0.062 (2)	0.078 (2)	0.093 (3)	0.0043 (19)	−0.012 (2)	0.018 (2)
N3	0.052 (2)	0.062 (3)	0.092 (3)	0.004 (2)	−0.009 (2)	0.017 (2)
C2A	0.059 (3)	0.057 (3)	0.080 (3)	0.004 (2)	−0.010 (3)	0.001 (2)
N1	0.079 (3)	0.056 (2)	0.067 (3)	0.003 (2)	0.019 (2)	−0.0038 (19)
C2'	0.052 (3)	0.065 (3)	0.061 (3)	0.008 (2)	−0.008 (2)	−0.004 (2)
O1	0.069 (2)	0.071 (2)	0.079 (2)	−0.003 (2)	−0.016 (2)	−0.0113 (18)
O08	0.112 (3)	0.059 (2)	0.088 (3)	−0.015 (2)	0.034 (3)	−0.0024 (18)
C1'	0.052 (2)	0.061 (3)	0.063 (3)	−0.004 (2)	0.012 (3)	0.001 (2)
O4	0.070 (2)	0.108 (3)	0.150 (5)	0.000 (3)	−0.012 (3)	0.067 (3)
O0	0.120 (4)	0.094 (3)	0.070 (3)	−0.017 (3)	0.036 (3)	−0.013 (2)
C1A	0.063 (3)	0.059 (3)	0.071 (3)	0.003 (3)	0.006 (3)	0.001 (2)
N2	0.066 (2)	0.058 (2)	0.072 (3)	0.006 (2)	−0.018 (2)	−0.0061 (19)
C3'	0.053 (3)	0.075 (3)	0.090 (4)	0.004 (3)	0.001 (3)	0.025 (3)
C01	0.111 (5)	0.060 (3)	0.105 (5)	−0.012 (4)	0.042 (5)	0.008 (3)
C0'	0.081 (3)	0.057 (3)	0.067 (3)	−0.005 (3)	0.011 (3)	0.005 (2)
C3A	0.067 (3)	0.074 (4)	0.111 (5)	−0.005 (3)	−0.021 (4)	0.032 (3)
C07	0.126 (6)	0.083 (4)	0.090 (4)	−0.039 (4)	0.032 (4)	−0.004 (3)

C02—C03	1.341 (15)	N3—H3	0.96 (7)
C02—C01	1.364 (12)	C2A—N2	1.435 (6)
C02—H02	0.9300	C2A—C2'	1.511 (7)
C3B—C3C	1.501 (16)	C2A—H2A1	0.9700
C3B—C3A	1.540 (11)	C2A—H2A2	0.9700
C3B—H3B1	0.9700	N1—C0'	1.333 (7)
C3B—H3B2	0.9700	N1—C1A	1.427 (6)
C06—C01	1.365 (12)	N1—H1	0.8600
C06—C05	1.428 (19)	O1—C1'	1.244 (6)
C06—H06	0.9300	O08—C0'	1.331 (6)
C3C—C3D	1.551 (17)	O08—C07	1.436 (7)
C3C—H3C1	0.9700	C1'—N2	1.317 (6)
C3C—H3C2	0.9700	C1'—C1A	1.513 (7)
C04—C05	1.28 (3)	O4—C3'	1.324 (7)
C04—C03	1.30 (2)	O4—H4	0.8200
C04—H04	0.9300	O0—C0'	1.216 (6)
C05—H05	0.9300	C1A—H1A1	0.9700
C03—H03	0.9300	C1A—H1A2	0.9700
C3D—H3D1	0.9600	N2—H2	0.8600
C3D—H3D2	0.9600	C3'—C3A	1.513 (8)
C3D—H3D3	0.9600	C01—C07	1.499 (9)
O3—C3'	1.185 (7)	C3A—H3A	1.01 (7)
O2—C2'	1.214 (6)	C07—H07A	0.9700
N3—C2'	1.343 (7)	C07—H07B	0.9700
N3—C3A	1.452 (8)
C03—C02—C01	120.1 (11)	C0'—N1—C1A	120.3 (4)
C03—C02—H02	119.9	C0'—N1—H1	119.9
C01—C02—H02	119.9	C1A—N1—H1	119.9
C3C—C3B—C3A	114.2 (7)	O2—C2'—N3	123.0 (5)
C3C—C3B—H3B1	108.7	O2—C2'—C2A	122.2 (5)
C3A—C3B—H3B1	108.7	N3—C2'—C2A	114.8 (4)
C3C—C3B—H3B2	108.7	C0'—O08—C07	118.6 (5)
C3A—C3B—H3B2	108.7	O1—C1'—N2	121.8 (5)
H3B1—C3B—H3B2	107.6	O1—C1'—C1A	121.0 (4)
C01—C06—C05	118.7 (14)	N2—C1'—C1A	117.1 (5)
C01—C06—H06	120.6	C3'—O4—H4	109.5
C05—C06—H06	120.6	N1—C1A—C1'	113.8 (4)
C3B—C3C—C3D	117.8 (13)	N1—C1A—H1A1	108.8
C3B—C3C—H3C1	107.8	C1'—C1A—H1A1	108.8
C3D—C3C—H3C1	107.8	N1—C1A—H1A2	108.8
C3B—C3C—H3C2	107.8	C1'—C1A—H1A2	108.8
C3D—C3C—H3C2	107.8	H1A1—C1A—H1A2	107.7
H3C1—C3C—H3C2	107.2	C1'—N2—C2A	123.5 (4)
C05—C04—C03	120.0 (17)	C1'—N2—H2	118.2
C05—C04—H04	120.0	C2A—N2—H2	118.2
C03—C04—H04	120.0	O3—C3'—O4	125.0 (5)
C04—C05—C06	120.7 (17)	O3—C3'—C3A	124.5 (5)
C04—C05—H05	119.6	O4—C3'—C3A	110.3 (5)
C06—C05—H05	119.6	C02—C01—C06	117.2 (8)
C04—C03—C02	123.2 (16)	C02—C01—C07	121.8 (8)
C04—C03—H03	118.4	C06—C01—C07	121.0 (9)
C02—C03—H03	118.4	O0—C0'—N1	124.4 (5)
C3C—C3D—H3D1	109.5	O0—C0'—O08	123.4 (5)
C3C—C3D—H3D2	109.5	N1—C0'—O08	112.2 (5)
H3D1—C3D—H3D2	109.5	N3—C3A—C3'	109.7 (5)
C3C—C3D—H3D3	109.5	N3—C3A—C3B	112.2 (6)
H3D1—C3D—H3D3	109.5	C3'—C3A—C3B	111.3 (6)
H3D2—C3D—H3D3	109.5	N3—C3A—H3A	107 (4)
C2'—N3—C3A	120.6 (4)	C3'—C3A—H3A	114 (4)
C2'—N3—H3	115 (4)	C3B—C3A—H3A	102 (4)
C3A—N3—H3	124 (4)	O08—C07—C01	108.0 (5)
N2—C2A—C2'	112.0 (4)	O08—C07—H07A	110.1
N2—C2A—H2A1	109.2	C01—C07—H07A	110.1
C2'—C2A—H2A1	109.2	O08—C07—H07B	110.1
N2—C2A—H2A2	109.2	C01—C07—H07B	110.1
C2'—C2A—H2A2	109.2	H07A—C07—H07B	108.4
H2A1—C2A—H2A2	107.9
C3A—C3B—C3C—C3D	−171.1 (13)	C05—C06—C01—C02	1.7 (16)
C03—C04—C05—C06	−3 (3)	C05—C06—C01—C07	−178.9 (11)
C01—C06—C05—C04	0 (3)	C1A—N1—C0'—O0	14.0 (9)
C05—C04—C03—C02	4 (3)	C1A—N1—C0'—O08	−167.9 (5)
C01—C02—C03—C04	−2 (2)	C07—O08—C0'—O0	−1.1 (10)
C3A—N3—C2'—O2	0.0 (9)	C07—O08—C0'—N1	−179.3 (6)
C3A—N3—C2'—C2A	−179.2 (5)	C2'—N3—C3A—C3'	−152.6 (6)
N2—C2A—C2'—O2	5.3 (7)	C2'—N3—C3A—C3B	83.1 (8)
N2—C2A—C2'—N3	−175.5 (5)	O3—C3'—C3A—N3	−18.6 (10)
C0'—N1—C1A—C1'	76.2 (7)	O4—C3'—C3A—N3	165.6 (6)
O1—C1'—C1A—N1	17.7 (7)	O3—C3'—C3A—C3B	106.2 (8)
N2—C1'—C1A—N1	−166.6 (4)	O4—C3'—C3A—C3B	−69.7 (8)
O1—C1'—N2—C2A	0.5 (8)	C3C—C3B—C3A—N3	57.1 (9)
C1A—C1'—N2—C2A	−175.2 (4)	C3C—C3B—C3A—C3'	−66.3 (9)
C2'—C2A—N2—C1'	133.1 (5)	C0'—O08—C07—C01	−173.7 (6)
C03—C02—C01—C06	−1.0 (14)	C02—C01—C07—O08	87.8 (9)
C03—C02—C01—C07	179.6 (9)	C06—C01—C07—O08	−91.5 (9)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O3i	0.86	2.47	3.061 (6)	127
N2—H2···O0ii	0.86	2.06	2.891 (6)	164
N3—H3···O2iii	0.96 (7)	2.36 (7)	3.268 (6)	159 (5)
O4—H4···O1iv	0.82	1.83	2.593 (5)	153

Table 1

Hydrogen-bond geometry (, )

DHA	DH	HA	D A	DHA
N1H1O3i	0.86	2.47	3.061(6)	127
N2H2O0ii	0.86	2.06	2.891(6)	164
N3H3O2iii	0.96(7)	2.36(7)	3.268(6)	159(5)
O4H4O1iv	0.82	1.83	2.593(5)	153

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .