(S)-2-[(2R,3S)-2-Ammonio-3-hydr-oxy-3-(4-nitro-phen-yl)propanamido]-4-methyl-penta-noate monohydrate.

The structure of the title compound, C(15)H(21)N(3)O(6)·H(2)O, is of inter-est with respect to assumed anti-cancer activity. The title mol-ecules are linked through inter-molecular O-H⋯O hydrogen-bonded chains along the a axis. These chains are connected by inter-molecular N-H⋯O hydrogen bonds through the crystallographic screw axis along [010], forming layers, which are stabilized by other N-H⋯O bonds with water O atoms as acceptors and O-H⋯O bonds with water H atoms as donors. The H atoms of the protonated amino cation are also involved in inter-molecular N-H⋯O bonding inter-actions.

Related literature

For various medicinal agents similar to the title compound, see: Shinagawa et al. (1987 ▶); Shin & Pyo (1984 ▶). For anti-cancer and anti-inflammatory biological properties, see: Aozuka et al. (2004 ▶). For amino­peptidase N (APN/CD13) inhibitors, see: Xu & Li (2005 ▶). For the synthesis of the starting material, see: Testa et al. (2004 ▶).

Experimental

Crystal data

C15H21N3O6·H2O

M = 357.36

Monoclinic,

a = 8.9787 (7) Å

b = 6.7850 (5) Å

c = 14.7148 (11) Å

β = 95.362 (5)°

V = 892.51 (12) Å3

Z = 2

Mo Kα radiation

μ = 0.11 mm−1

T = 296 (2) K

0.50 × 0.20 × 0.15 mm

Data collection

Bruker APEXII CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T min = 0.949, T max = 0.984

8245 measured reflections

2254 independent reflections

1853 reflections with I > 2σ(I)

R int = 0.028

Refinement

R[F 2 > 2σ(F 2)] = 0.041

wR(F 2) = 0.104

S = 1.04

2254 reflections

243 parameters

1 restraint

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.19 e Å−3

Δρmin = −0.16 e Å−3

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: APEX2 and SAINT (Bruker, 2005 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808039056/si2128sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808039056/si2128Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C15H21N3O6·H2O	F000 = 380
Mr = 357.36	Dx = 1.330 Mg m−3
Monoclinic, P21	Melting point = 556.2–558.6 K
Hall symbol: P 2yb	Mo Kα radiation λ = 0.71073 Å
a = 8.9787 (7) Å	Cell parameters from 2639 reflections
b = 6.7850 (5) Å	θ = 2.8–24.2º
c = 14.7148 (11) Å	µ = 0.11 mm−1
β = 95.362 (5)º	T = 296 (2) K
V = 892.51 (12) Å3	Prism, colourless
Z = 2	0.50 × 0.20 × 0.15 mm

Bruker APEXII CCD area-detector diffractometer	2254 independent reflections
Radiation source: fine-focus sealed tube	1853 reflections with I > 2σ(I)
Monochromator: graphite	Rint = 0.028
T = 296(2) K	θmax = 27.6º
φ and ω scans	θmin = 2.3º
Absorption correction: multi-scan(SADABS; Bruker, 2005)	h = −11→11
Tmin = 0.949, Tmax = 0.984	k = −8→8
8245 measured reflections	l = −19→18

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)] = 0.041	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.105	w = 1/[σ2(Fo2) + (0.059P)2 + 0.0778P] where P = (Fo2 + 2Fc2)/3
S = 1.04	(Δ/σ)max < 0.001
2254 reflections	Δρmax = 0.19 e Å−3
243 parameters	Δρmin = −0.16 e Å−3
1 restraint	Extinction correction: none
Primary atom site location: structure-invariant direct methods

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
C1	0.1171 (3)	1.0193 (5)	0.8450 (2)	0.0593 (8)
C2	0.1386 (3)	1.1114 (5)	0.7646 (2)	0.0576 (8)
H2	0.1620	1.2449	0.7637	0.069*
C3	0.1250 (3)	1.0037 (4)	0.68503 (19)	0.0466 (6)
H10	0.1388	1.0647	0.6298	0.056*
C4	0.0906 (2)	0.8025 (4)	0.68693 (16)	0.0350 (5)
C5	0.0699 (3)	0.7141 (5)	0.76921 (18)	0.0487 (7)
H5	0.0466	0.5806	0.7708	0.058*
C6	0.0834 (3)	0.8219 (6)	0.8498 (2)	0.0627 (9)
H6	0.0700	0.7624	0.9053	0.075*
C7	0.0792 (2)	0.6835 (4)	0.59945 (16)	0.0320 (5)
H7	0.0586	0.5457	0.6137	0.038*
C8	0.2268 (2)	0.6944 (3)	0.55531 (14)	0.0303 (5)
H8	0.2570	0.8326	0.5509	0.036*
C9	0.3482 (2)	0.5812 (4)	0.61333 (15)	0.0313 (5)
C10	0.7060 (2)	0.5166 (4)	0.64655 (17)	0.0386 (6)
C11	0.5895 (2)	0.6028 (4)	0.70569 (15)	0.0368 (5)
H11	0.5533	0.4984	0.7441	0.044*
C12	0.6643 (3)	0.7644 (5)	0.76667 (18)	0.0469 (6)
H12A	0.7440	0.7047	0.8064	0.056*
H12B	0.7100	0.8583	0.7280	0.056*
C13	0.5625 (4)	0.8776 (7)	0.8260 (2)	0.0707 (10)
H13	0.4790	0.9317	0.7860	0.085*
C14	0.6501 (6)	1.0509 (8)	0.8721 (3)	0.1067 (16)
H14A	0.7269	1.0011	0.9159	0.160*
H14B	0.5832	1.1331	0.9025	0.160*
H14C	0.6950	1.1266	0.8268	0.160*
C15	0.4992 (5)	0.7477 (10)	0.8948 (3)	0.1045 (17)
H15A	0.5792	0.6944	0.9353	0.157*
H15B	0.4442	0.6420	0.8640	0.157*
H15C	0.4337	0.8232	0.9292	0.157*
N1	0.1333 (4)	1.1348 (8)	0.9301 (3)	0.0933 (13)
N2	0.2080 (2)	0.6066 (3)	0.46217 (14)	0.0345 (4)
N3	0.46309 (18)	0.6869 (3)	0.64893 (13)	0.0346 (4)
H3A	0.4634	0.8115	0.6381	0.042*
O1	0.1562 (6)	1.3125 (7)	0.9239 (3)	0.1463 (17)
O2	0.1267 (4)	1.0520 (8)	1.0013 (2)	0.1297 (16)
O3	−0.03561 (16)	0.7538 (3)	0.53411 (11)	0.0371 (4)
H4	−0.1147	0.6988	0.5420	0.056*
O4	0.33299 (19)	0.4031 (3)	0.62517 (14)	0.0482 (5)
O5	0.71194 (18)	0.5906 (3)	0.56790 (12)	0.0471 (5)
O6	0.7901 (2)	0.3852 (3)	0.67915 (14)	0.0548 (5)
O7	0.50705 (17)	0.5833 (3)	0.42343 (12)	0.0410 (4)
H7W	0.5421	0.5886	0.4840	0.086 (12)*
H8W	0.5327	0.6792	0.3873	0.071 (10)*
H2B	0.154 (3)	0.500 (5)	0.4578 (19)	0.045 (8)*
H2C	0.162 (4)	0.702 (5)	0.416 (2)	0.055 (8)*
H2A	0.305 (4)	0.564 (5)	0.448 (2)	0.060 (9)*

	U11	U22	U33	U12	U13	U23
C1	0.0459 (16)	0.076 (2)	0.0564 (18)	0.0056 (15)	0.0037 (13)	−0.0238 (17)
C2	0.0583 (18)	0.0473 (16)	0.0666 (19)	0.0060 (14)	0.0025 (14)	−0.0134 (16)
C3	0.0478 (15)	0.0390 (14)	0.0530 (16)	0.0044 (12)	0.0046 (12)	−0.0038 (13)
C4	0.0207 (10)	0.0405 (13)	0.0438 (13)	0.0056 (9)	0.0035 (9)	−0.0001 (11)
C5	0.0405 (14)	0.0568 (18)	0.0502 (15)	−0.0030 (12)	0.0117 (11)	0.0034 (14)
C6	0.0536 (17)	0.092 (3)	0.0436 (16)	−0.0035 (18)	0.0122 (13)	0.0009 (17)
C7	0.0198 (9)	0.0319 (10)	0.0443 (12)	0.0009 (9)	0.0030 (8)	0.0040 (10)
C8	0.0212 (10)	0.0278 (10)	0.0420 (12)	−0.0012 (8)	0.0041 (8)	−0.0011 (10)
C9	0.0234 (10)	0.0322 (12)	0.0389 (11)	0.0043 (9)	0.0063 (8)	−0.0008 (10)
C10	0.0236 (10)	0.0444 (14)	0.0469 (14)	−0.0012 (10)	−0.0007 (9)	−0.0097 (11)
C11	0.0246 (10)	0.0462 (14)	0.0394 (12)	0.0048 (10)	0.0019 (8)	0.0056 (11)
C12	0.0376 (13)	0.0602 (16)	0.0419 (13)	0.0076 (12)	−0.0014 (10)	−0.0077 (13)
C13	0.0663 (19)	0.099 (3)	0.0454 (16)	0.034 (2)	−0.0050 (14)	−0.0190 (18)
C14	0.143 (4)	0.097 (3)	0.079 (3)	0.024 (3)	−0.001 (3)	−0.040 (3)
C15	0.084 (3)	0.170 (5)	0.064 (2)	0.017 (3)	0.0297 (19)	−0.009 (3)
N1	0.085 (2)	0.126 (4)	0.069 (2)	0.004 (2)	0.0054 (17)	−0.041 (2)
N2	0.0247 (10)	0.0361 (11)	0.0433 (11)	−0.0023 (9)	0.0057 (8)	−0.0012 (10)
N3	0.0223 (9)	0.0356 (10)	0.0458 (11)	−0.0005 (8)	0.0027 (7)	0.0025 (9)
O1	0.222 (5)	0.107 (3)	0.105 (3)	0.002 (3)	−0.009 (3)	−0.062 (3)
O2	0.155 (3)	0.180 (4)	0.0575 (16)	−0.041 (3)	0.0267 (18)	−0.043 (2)
O3	0.0214 (7)	0.0398 (9)	0.0495 (9)	0.0015 (7)	0.0012 (6)	0.0023 (8)
O4	0.0373 (9)	0.0318 (9)	0.0742 (12)	0.0033 (8)	−0.0014 (8)	0.0039 (9)
O5	0.0272 (8)	0.0707 (13)	0.0439 (10)	0.0003 (9)	0.0073 (7)	−0.0007 (10)
O6	0.0444 (10)	0.0550 (12)	0.0641 (12)	0.0190 (10)	0.0003 (9)	−0.0045 (10)
O7	0.0323 (8)	0.0407 (9)	0.0507 (10)	−0.0021 (8)	0.0070 (7)	0.0013 (9)

C1—C2	1.368 (5)	C11—C12	1.532 (4)
C1—C6	1.376 (5)	C11—H11	0.9800
C1—N1	1.473 (4)	C12—C13	1.528 (4)
C2—C3	1.376 (4)	C12—H12A	0.9700
C2—H2	0.9300	C12—H12B	0.9700
C3—C4	1.401 (4)	C13—C15	1.494 (6)
C3—H10	0.9300	C13—C14	1.537 (6)
C4—C5	1.379 (3)	C13—H13	0.9800
C4—C7	1.515 (3)	C14—H14A	0.9600
C5—C6	1.388 (4)	C14—H14B	0.9600
C5—H5	0.9300	C14—H14C	0.9600
C6—H6	0.9300	C15—H15A	0.9600
C7—O3	1.424 (3)	C15—H15B	0.9600
C7—C8	1.531 (3)	C15—H15C	0.9600
C7—H7	0.9800	N1—O2	1.195 (6)
C8—N2	1.489 (3)	N1—O1	1.228 (7)
C8—C9	1.528 (3)	N2—H2B	0.87 (3)
C8—H8	0.9800	N2—H2C	0.99 (3)
C9—O4	1.231 (3)	N2—H2A	0.95 (3)
C9—N3	1.323 (3)	N3—H3A	0.8600
C10—O6	1.236 (3)	O3—H4	0.8200
C10—O5	1.267 (3)	O7—H7W	0.9174
C10—C11	1.538 (3)	O7—H8W	0.8845
C11—N3	1.461 (3)
C2—C1—C6	122.5 (3)	C12—C11—H11	109.3
C2—C1—N1	118.8 (4)	C10—C11—H11	109.3
C6—C1—N1	118.6 (4)	C13—C12—C11	116.2 (2)
C1—C2—C3	119.0 (3)	C13—C12—H12A	108.2
C1—C2—H2	120.5	C11—C12—H12A	108.2
C3—C2—H2	120.5	C13—C12—H12B	108.2
C2—C3—C4	120.2 (3)	C11—C12—H12B	108.2
C2—C3—H10	119.9	H12A—C12—H12B	107.4
C4—C3—H10	119.9	C15—C13—C12	112.1 (4)
C5—C4—C3	119.3 (3)	C15—C13—C14	111.3 (3)
C5—C4—C7	120.7 (2)	C12—C13—C14	109.2 (3)
C3—C4—C7	120.0 (2)	C15—C13—H13	108.1
C4—C5—C6	120.8 (3)	C12—C13—H13	108.1
C4—C5—H5	119.6	C14—C13—H13	108.1
C6—C5—H5	119.6	C13—C14—H14A	109.5
C1—C6—C5	118.1 (3)	C13—C14—H14B	109.5
C1—C6—H6	120.9	H14A—C14—H14B	109.5
C5—C6—H6	120.9	C13—C14—H14C	109.5
O3—C7—C4	112.48 (18)	H14A—C14—H14C	109.5
O3—C7—C8	107.33 (17)	H14B—C14—H14C	109.5
C4—C7—C8	110.03 (18)	C13—C15—H15A	109.5
O3—C7—H7	109.0	C13—C15—H15B	109.5
C4—C7—H7	109.0	H15A—C15—H15B	109.5
C8—C7—H7	109.0	C13—C15—H15C	109.5
N2—C8—C9	109.07 (18)	H15A—C15—H15C	109.5
N2—C8—C7	110.07 (17)	H15B—C15—H15C	109.5
C9—C8—C7	109.85 (18)	O2—N1—O1	123.3 (4)
N2—C8—H8	109.3	O2—N1—C1	119.1 (5)
C9—C8—H8	109.3	O1—N1—C1	117.6 (4)
C7—C8—H8	109.3	C8—N2—H2B	114.5 (19)
O4—C9—N3	124.7 (2)	C8—N2—H2C	111.6 (18)
O4—C9—C8	119.3 (2)	H2B—N2—H2C	107 (3)
N3—C9—C8	116.0 (2)	C8—N2—H2A	107.1 (19)
O6—C10—O5	124.3 (2)	H2B—N2—H2A	104 (3)
O6—C10—C11	118.5 (2)	H2C—N2—H2A	112 (3)
O5—C10—C11	117.1 (2)	C9—N3—C11	123.3 (2)
N3—C11—C12	109.3 (2)	C9—N3—H3A	118.3
N3—C11—C10	111.00 (19)	C11—N3—H3A	118.3
C12—C11—C10	108.64 (19)	C7—O3—H4	109.5
N3—C11—H11	109.3	H7W—O7—H8W	118.1
C6—C1—C2—C3	0.5 (5)	C7—C8—C9—O4	61.9 (3)
N1—C1—C2—C3	179.3 (3)	N2—C8—C9—N3	122.4 (2)
C1—C2—C3—C4	−0.3 (4)	C7—C8—C9—N3	−116.9 (2)
C2—C3—C4—C5	0.2 (4)	O6—C10—C11—N3	−155.5 (2)
C2—C3—C4—C7	−178.6 (2)	O5—C10—C11—N3	26.6 (3)
C3—C4—C5—C6	−0.2 (4)	O6—C10—C11—C12	84.4 (3)
C7—C4—C5—C6	178.6 (2)	O5—C10—C11—C12	−93.6 (3)
C2—C1—C6—C5	−0.5 (5)	N3—C11—C12—C13	54.7 (3)
N1—C1—C6—C5	−179.3 (3)	C10—C11—C12—C13	175.9 (3)
C4—C5—C6—C1	0.4 (4)	C11—C12—C13—C15	64.0 (4)
C5—C4—C7—O3	119.8 (2)	C11—C12—C13—C14	−172.3 (3)
C3—C4—C7—O3	−61.3 (3)	C2—C1—N1—O2	−174.0 (4)
C5—C4—C7—C8	−120.6 (2)	C6—C1—N1—O2	4.9 (5)
C3—C4—C7—C8	58.2 (3)	C2—C1—N1—O1	4.6 (6)
O3—C7—C8—N2	−47.8 (2)	C6—C1—N1—O1	−176.5 (4)
C4—C7—C8—N2	−170.52 (19)	O4—C9—N3—C11	1.5 (3)
O3—C7—C8—C9	−167.95 (18)	C8—C9—N3—C11	−179.66 (19)
C4—C7—C8—C9	69.4 (2)	C12—C11—N3—C9	−156.1 (2)
N2—C8—C9—O4	−58.8 (3)	C10—C11—N3—C9	84.1 (3)

D—H···A	D—H	H···A	D···A	D—H···A
O7—H7W···O5	0.92	1.87	2.679 (2)	146
O7—H8W···O4i	0.88	1.96	2.734 (3)	146
N2—H2B···O3ii	0.87 (3)	1.99 (3)	2.854 (3)	172 (3)
O3—H4···O5iii	0.82	1.79	2.612 (2)	175
N3—H3A···O7i	0.86	2.08	2.914 (3)	163
N2—H2C···O6i	0.99 (3)	1.96 (3)	2.811 (3)	143 (3)
N2—H2A···O7	0.95 (3)	1.89 (3)	2.801 (2)	158 (3)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O7—H7W⋯O5	0.92	1.87	2.679 (2)	146
O7—H8W⋯O4i	0.88	1.96	2.734 (3)	146
N2—H2B⋯O3ii	0.87 (3)	1.99 (3)	2.854 (3)	172 (3)
O3—H4⋯O5iii	0.82	1.79	2.612 (2)	175
N3—H3A⋯O7i	0.86	2.08	2.914 (3)	163
N2—H2C⋯O6i	0.99 (3)	1.96 (3)	2.811 (3)	143 (3)
N2—H2A⋯O7	0.95 (3)	1.89 (3)	2.801 (2)	158 (3)

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