Buy article online - an online subscription or single-article purchase is required to access this article.
The title compound, C19H23N2O5P, is one of two diastereomers of an arylphosphonamide hydroxamate. The absolute configuration has been determined to establish the relationship between the stereochemistry at the P atom and the activity in inhibition of matrix metalloproteinases.
Supporting information
CCDC reference: 175349
Key indicators
- Single-crystal X-ray study
- T = 294 K
- Mean (C-C) = 0.004 Å
- R factor = 0.041
- wR factor = 0.102
- Data-to-parameter ratio = 10.6
checkCIF results
No syntax errors found
ADDSYM reports no extra symmetry
Alert Level A:
PLAT_706 Alert A H...A Calc 44.44(2), Rep 2.12(2), Dev. 2116.00 Sigma
H10 -O1 1.555 3.566
PLAT_707 Alert A D...A Calc 44.458(9), Rep 2.951(2), Dev. 4611.89 Sigma
N2 -O1 1.555 3.566
PLAT_708 Alert A D-H..A Calc 90.3(14), Rep 158(2), Dev. 48.36 Sigma
N2 -H10 -O1 1.555 1.555 3.566
Alert Level B:
THETM_01 Alert B The value of sine(theta_max)/wavelength is less than 0.575
Calculated sin(theta_max)/wavelength = 0.5726
General Notes
REFLT_03
From the CIF: _diffrn_reflns_theta_max 61.99
From the CIF: _reflns_number_total 3303
Count of symmetry unique reflns 1731
Completeness (_total/calc) 190.81%
TEST3: Check Friedels for noncentro structure
Estimate of Friedel pairs measured 1572
Fraction of Friedel pairs measured 0.908
Are heavy atom types Z>Si present yes
Please check that the estimate of the number of Friedel pairs is
correct. If it is not, please give the correct count in the
_publ_section_exptl_refinement section of the submitted CIF.
3 Alert Level A = Potentially serious problem
1 Alert Level B = Potential problem
0 Alert Level C = Please check
The synthesis of the title compound is reported elsewhere (Sawa et al.,
2001). Crystals of (I) were obtained by recrystallization from EtOH at 293 K.
The melting point of (I) is 440.0–440.5 K. The optical rotation of (I),
[α]D20, is +68.43° (c 1.02, MeOH) and that of (II) is +18.48° (c 1.10,
MeOH).
θmax(Cu Kα) = 62°, which was lower than 67°, because of the restriction of
the diffractometer. The methyl H atoms on C12 and C19 were placed at
geometrically idealized positions (C—H = 0.95 Å) and not refined. All
other H atoms were found from the difference Fourier maps and refined
isotropically. The C—H, N—H and O—H bond lengths are 0.90 (3)–1.07 (4),
0.88 (3) and 0.90 (4) Å, respectively.
Data collection: Rigaku/AFC Diffractometer Control (Rigaku, 1998); cell refinement: Rigaku/AFC Diffractometer Control; data reduction: TEXSAN (Molecular Structure Corporation, 1999); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: TEXSAN; molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: TEXSAN.
Crystal data top
C19H23N2O5P | Dx = 1.364 Mg m−3 |
Mr = 390.37 | Melting point: 440-440.5K K |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.5418 Å |
a = 10.156 (2) Å | Cell parameters from 21 reflections |
b = 19.733 (1) Å | θ = 27.5–30.0° |
c = 9.486 (1) Å | µ = 1.57 mm−1 |
V = 1901.1 (3) Å3 | T = 294 K |
Z = 4 | Prismatic, colorless |
F(000) = 824.00 | 0.20 × 0.10 × 0.10 mm |
Data collection top
Rigaku AFC-5R diffractometer | Rint = 0.016 |
ω–2θ scans | θmax = 62.0° |
Absorption correction: ψ scan (North et al., 1968) | h = −9→11 |
Tmin = 0.757, Tmax = 0.854 | k = −22→22 |
3303 measured reflections | l = −10→10 |
3303 independent reflections | 3 standard reflections every 150 reflections |
2991 reflections with F2 > 2σ(F2) | intensity decay: 3.7% |
Refinement top
Refinement on F2 | w = 1/[σ2(Fo2) + {0.019[Max(Fo2,0) + 2Fc2]/3}2] |
R[F2 > 2σ(F2)] = 0.041 | (Δ/σ)max = 0.013 |
wR(F2) = 0.102 | Δρmax = 0.17 e Å−3 |
S = 1.65 | Δρmin = −0.20 e Å−3 |
3303 reflections | Absolute structure: Flack (1983), 1571 Friedel pairs |
313 parameters | Absolute structure parameter: 0.01 (3) |
H atoms treated by a mixture of independent and constrained refinement | |
Crystal data top
C19H23N2O5P | V = 1901.1 (3) Å3 |
Mr = 390.37 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 10.156 (2) Å | µ = 1.57 mm−1 |
b = 19.733 (1) Å | T = 294 K |
c = 9.486 (1) Å | 0.20 × 0.10 × 0.10 mm |
Data collection top
Rigaku AFC-5R diffractometer | 2991 reflections with F2 > 2σ(F2) |
Absorption correction: ψ scan (North et al., 1968) | Rint = 0.016 |
Tmin = 0.757, Tmax = 0.854 | θmax = 62.0° |
3303 measured reflections | 3 standard reflections every 150 reflections |
3303 independent reflections | intensity decay: 3.7% |
Refinement top
R[F2 > 2σ(F2)] = 0.041 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.102 | Δρmax = 0.17 e Å−3 |
S = 1.65 | Δρmin = −0.20 e Å−3 |
3303 reflections | Absolute structure: Flack (1983), 1571 Friedel pairs |
313 parameters | Absolute structure parameter: 0.01 (3) |
Special details top
Refinement. Refinement using reflections with F2 > -10.0 σ(F2). 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) top | x | y | z | Uiso*/Ueq | |
P1 | −0.56426 (6) | −0.21711 (3) | −0.84469 (6) | 0.0333 (1) | |
O1 | −0.9337 (2) | −0.2599 (1) | −0.5117 (2) | 0.0560 (6) | |
O2 | −0.7287 (2) | −0.3095 (1) | −0.3626 (2) | 0.0580 (6) | |
O3 | −0.4248 (2) | −0.19923 (9) | −0.8208 (2) | 0.0477 (5) | |
O4 | −0.6258 (2) | −0.17889 (9) | −0.9759 (2) | 0.0408 (5) | |
O5 | −0.6213 (2) | −0.51177 (10) | −0.9532 (3) | 0.0773 (7) | |
N1 | −0.6571 (2) | −0.19471 (10) | −0.7116 (2) | 0.0327 (5) | |
N2 | −0.7173 (2) | −0.2728 (1) | −0.4865 (2) | 0.0404 (6) | |
C1 | −0.6238 (2) | −0.1313 (1) | −0.6357 (3) | 0.0369 (7) | |
C2 | −0.7937 (2) | −0.2187 (1) | −0.6989 (2) | 0.0341 (6) | |
C3 | −0.8914 (3) | −0.1622 (1) | −0.7332 (3) | 0.0398 (7) | |
C4 | −0.9687 (3) | −0.0586 (2) | −0.6001 (4) | 0.0548 (9) | |
C5 | −0.9445 (3) | −0.0036 (2) | −0.5150 (4) | 0.0646 (9) | |
C6 | −0.8180 (3) | 0.0092 (1) | −0.4663 (4) | 0.0605 (9) | |
C7 | −0.7159 (3) | −0.0334 (1) | −0.5056 (3) | 0.0474 (8) | |
C8 | −0.7386 (2) | −0.0884 (1) | −0.5939 (2) | 0.0358 (6) | |
C9 | −0.8658 (2) | −0.1018 (1) | −0.6419 (3) | 0.0385 (6) | |
C10 | −0.8202 (3) | −0.2513 (1) | −0.5558 (3) | 0.0355 (6) | |
C11 | −0.5551 (4) | −0.1765 (2) | −1.1094 (3) | 0.0562 (9) | |
C12 | −0.6434 (4) | −0.1502 (2) | −1.2186 (3) | 0.080 (1) | |
C13 | −0.5915 (2) | −0.3055 (1) | −0.8773 (2) | 0.0372 (6) | |
C14 | −0.6706 (3) | −0.3284 (1) | −0.9858 (3) | 0.0410 (7) | |
C15 | −0.6843 (3) | −0.3969 (1) | −1.0160 (3) | 0.0493 (8) | |
C16 | −0.6160 (3) | −0.4430 (1) | −0.9350 (3) | 0.0531 (8) | |
C17 | −0.5378 (3) | −0.4211 (2) | −0.8238 (4) | 0.0640 (9) | |
C18 | −0.5236 (3) | −0.3534 (2) | −0.7955 (3) | 0.0551 (8) | |
C19 | −0.6829 (4) | −0.5385 (2) | −1.0744 (5) | 0.081 (1) | |
H1 | −0.570 (3) | −0.102 (1) | −0.691 (3) | 0.052 (8)* | |
H2 | −0.574 (2) | −0.138 (1) | −0.558 (3) | 0.031 (6)* | |
H3 | −0.814 (2) | −0.253 (1) | −0.764 (2) | 0.025 (6)* | |
H4 | −0.881 (2) | −0.149 (1) | −0.838 (3) | 0.038 (6)* | |
H5 | −0.974 (2) | −0.178 (1) | −0.719 (2) | 0.030 (6)* | |
H6 | −1.058 (3) | −0.071 (1) | −0.628 (3) | 0.046 (7)* | |
H7 | −1.016 (3) | 0.024 (1) | −0.482 (3) | 0.052 (8)* | |
H8 | −0.794 (3) | 0.045 (1) | −0.406 (3) | 0.063 (9)* | |
H9 | −0.624 (2) | −0.024 (1) | −0.473 (3) | 0.037 (7)* | |
H10 | −0.633 (2) | −0.270 (1) | −0.507 (3) | 0.035 (7)* | |
H11 | −0.803 (3) | −0.301 (2) | −0.314 (3) | 0.08 (1)* | |
H12 | −0.517 (3) | −0.218 (1) | −1.133 (3) | 0.051 (8)* | |
H13 | −0.471 (3) | −0.144 (1) | −1.102 (3) | 0.069 (9)* | |
H14 | −0.6798 | −0.1082 | −1.1873 | 0.0968* | |
H15 | −0.5952 | −0.1431 | −1.3025 | 0.0968* | |
H16 | −0.7122 | −0.1816 | −1.2344 | 0.0968* | |
H17 | −0.727 (3) | −0.301 (1) | −1.039 (3) | 0.054 (8)* | |
H18 | −0.745 (3) | −0.412 (1) | −1.093 (3) | 0.051 (8)* | |
H19 | −0.484 (3) | −0.448 (1) | −0.777 (3) | 0.056 (9)* | |
H20 | −0.470 (3) | −0.339 (1) | −0.716 (3) | 0.059 (8)* | |
H21 | −0.7720 | −0.5242 | −1.0776 | 0.0950* | |
H22 | −0.6384 | −0.5224 | −1.1567 | 0.0950* | |
H23 | −0.6790 | −0.5865 | −1.0726 | 0.0950* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
P1 | 0.0284 (3) | 0.0447 (3) | 0.0267 (3) | 0.0009 (3) | 0.0019 (3) | 0.0008 (3) |
O1 | 0.0266 (9) | 0.071 (1) | 0.070 (1) | −0.0017 (9) | 0.007 (1) | 0.028 (1) |
O2 | 0.043 (1) | 0.076 (1) | 0.055 (1) | 0.012 (1) | 0.013 (1) | 0.033 (1) |
O3 | 0.0313 (8) | 0.074 (1) | 0.0381 (9) | −0.0069 (9) | 0.0054 (8) | 0.0000 (9) |
O4 | 0.046 (1) | 0.0471 (10) | 0.0293 (8) | 0.0045 (9) | 0.0027 (8) | 0.0024 (7) |
O5 | 0.084 (2) | 0.0412 (10) | 0.107 (2) | 0.004 (1) | −0.010 (2) | −0.003 (1) |
N1 | 0.0277 (10) | 0.041 (1) | 0.0293 (10) | −0.0048 (8) | 0.0006 (8) | −0.0035 (8) |
N2 | 0.027 (1) | 0.055 (1) | 0.039 (1) | −0.0001 (10) | 0.0072 (10) | 0.0083 (10) |
C1 | 0.033 (1) | 0.041 (1) | 0.037 (1) | −0.004 (1) | −0.005 (1) | −0.001 (1) |
C2 | 0.029 (1) | 0.040 (1) | 0.034 (1) | −0.0047 (10) | −0.001 (1) | −0.007 (1) |
C3 | 0.029 (1) | 0.054 (1) | 0.036 (1) | −0.001 (1) | −0.006 (1) | 0.004 (1) |
C4 | 0.043 (2) | 0.054 (2) | 0.068 (2) | 0.011 (1) | 0.010 (1) | 0.014 (1) |
C5 | 0.063 (2) | 0.045 (1) | 0.087 (2) | 0.015 (1) | 0.028 (2) | 0.003 (1) |
C6 | 0.073 (2) | 0.040 (2) | 0.068 (2) | 0.004 (1) | 0.015 (2) | −0.008 (2) |
C7 | 0.056 (2) | 0.041 (1) | 0.045 (1) | −0.006 (1) | 0.000 (1) | −0.001 (1) |
C8 | 0.040 (1) | 0.036 (1) | 0.031 (1) | 0.001 (1) | 0.001 (1) | 0.0083 (9) |
C9 | 0.038 (1) | 0.042 (1) | 0.036 (1) | 0.0017 (10) | 0.001 (1) | 0.0132 (10) |
C10 | 0.029 (1) | 0.036 (1) | 0.041 (1) | 0.000 (1) | 0.005 (1) | −0.001 (1) |
C11 | 0.077 (2) | 0.057 (2) | 0.035 (1) | 0.006 (2) | 0.021 (1) | 0.002 (1) |
C12 | 0.125 (3) | 0.084 (2) | 0.030 (1) | 0.006 (2) | −0.009 (2) | 0.007 (2) |
C13 | 0.035 (1) | 0.046 (1) | 0.031 (1) | 0.009 (1) | 0.0025 (10) | −0.0006 (10) |
C14 | 0.037 (1) | 0.047 (1) | 0.039 (1) | 0.007 (1) | −0.005 (1) | 0.000 (1) |
C15 | 0.043 (2) | 0.050 (1) | 0.054 (2) | −0.002 (1) | −0.005 (1) | −0.004 (1) |
C16 | 0.052 (2) | 0.043 (1) | 0.064 (2) | 0.006 (1) | 0.008 (1) | 0.003 (1) |
C17 | 0.072 (2) | 0.051 (1) | 0.070 (2) | 0.019 (2) | −0.018 (2) | 0.009 (2) |
C18 | 0.064 (2) | 0.055 (1) | 0.046 (2) | 0.015 (1) | −0.017 (1) | −0.001 (1) |
C19 | 0.077 (3) | 0.052 (2) | 0.113 (3) | −0.008 (2) | 0.009 (2) | −0.024 (2) |
Geometric parameters (Å, º) top
P1—O3 | 1.477 (2) | C15—C16 | 1.378 (5) |
P1—O4 | 1.584 (2) | C16—C17 | 1.389 (6) |
P1—N1 | 1.636 (3) | C17—C18 | 1.372 (5) |
P1—C13 | 1.793 (3) | O2—H11 | 0.90 (4) |
O1—C10 | 1.238 (4) | N2—H10 | 0.88 (3) |
O2—N2 | 1.386 (4) | C1—H1 | 0.95 (3) |
O4—C11 | 1.456 (4) | C1—H2 | 0.90 (3) |
O5—C16 | 1.369 (4) | C2—H3 | 0.94 (3) |
O5—C19 | 1.411 (6) | C3—H4 | 1.03 (3) |
N1—C1 | 1.482 (4) | C3—H5 | 0.91 (3) |
N1—C2 | 1.471 (4) | C4—H6 | 0.97 (3) |
N2—C10 | 1.305 (4) | C5—H7 | 0.95 (3) |
C1—C8 | 1.494 (4) | C6—H8 | 0.95 (4) |
C2—C3 | 1.526 (4) | C7—H9 | 1.00 (3) |
C2—C10 | 1.526 (4) | C11—H12 | 0.93 (3) |
C3—C9 | 1.496 (5) | C11—H13 | 1.07 (4) |
C4—C5 | 1.376 (6) | C12—H14 | 0.954 |
C4—C9 | 1.406 (5) | C12—H15 | 0.945 |
C5—C6 | 1.388 (6) | C12—H16 | 0.946 |
C6—C7 | 1.387 (5) | C14—H17 | 0.94 (3) |
C7—C8 | 1.390 (4) | C15—H18 | 1.00 (3) |
C8—C9 | 1.395 (4) | C17—H19 | 0.88 (4) |
C11—C12 | 1.466 (6) | C18—H20 | 0.97 (4) |
C13—C14 | 1.381 (4) | C19—H21 | 0.948 |
C13—C18 | 1.404 (5) | C19—H22 | 0.957 |
C14—C15 | 1.389 (4) | C19—H23 | 0.949 |
| | | |
O1···N2i | 2.951 (4) | O2···C3iii | 3.588 (4) |
O1···C1i | 3.209 (4) | O3···C14iv | 3.214 (4) |
O1···N1i | 3.231 (4) | O3···C15iv | 3.458 (4) |
O1···O3i | 3.257 (4) | O4···C6v | 3.398 (4) |
O1···O2i | 3.503 (4) | O5···C7vi | 3.473 (5) |
O2···O3i | 2.650 (3) | O5···C1vi | 3.532 (4) |
O2···C12ii | 3.536 (6) | N2···C12ii | 3.588 (5) |
| | | |
O3—P1—O4 | 112.6 (1) | N1—C1—H2 | 113 (2) |
O3—P1—N1 | 111.7 (1) | C8—C1—H1 | 105 (2) |
O3—P1—C13 | 114.0 (1) | C8—C1—H2 | 108 (2) |
O4—P1—N1 | 104.5 (1) | H1—C1—H2 | 103 (3) |
O4—P1—C13 | 105.5 (1) | N1—C2—H3 | 113 (2) |
N1—P1—C13 | 107.9 (1) | C3—C2—H3 | 104 (2) |
P1—O4—C11 | 120.3 (2) | C10—C2—H3 | 105 (2) |
C16—O5—C19 | 119.3 (4) | C2—C3—H4 | 109 (2) |
P1—N1—C1 | 118.1 (2) | C2—C3—H5 | 109 (2) |
P1—N1—C2 | 121.4 (2) | C9—C3—H4 | 109 (2) |
C1—N1—C2 | 116.5 (2) | C9—C3—H5 | 110 (2) |
O2—N2—C10 | 122.0 (3) | H4—C3—H5 | 109 (3) |
N1—C1—C8 | 115.4 (3) | C5—C4—H6 | 121 (2) |
N1—C2—C3 | 111.2 (3) | C9—C4—H6 | 118 (2) |
N1—C2—C10 | 112.0 (3) | C4—C5—H7 | 120 (2) |
C3—C2—C10 | 112.5 (3) | C6—C5—H7 | 120 (2) |
C2—C3—C9 | 110.2 (3) | C5—C6—H8 | 125 (2) |
C5—C4—C9 | 120.8 (4) | C7—C6—H8 | 116 (2) |
C4—C5—C6 | 120.2 (4) | C6—C7—H9 | 120 (2) |
C5—C6—C7 | 119.5 (4) | C8—C7—H9 | 119 (2) |
C6—C7—C8 | 120.8 (4) | O4—C11—H12 | 112 (2) |
C1—C8—C7 | 118.2 (3) | O4—C11—H13 | 111 (2) |
C1—C8—C9 | 121.9 (3) | C12—C11—H12 | 113 (2) |
C7—C8—C9 | 119.9 (3) | C12—C11—H13 | 109 (2) |
C3—C9—C4 | 121.1 (3) | H12—C11—H13 | 102 (3) |
C3—C9—C8 | 120.1 (3) | C11—C12—H14 | 108.96 |
C4—C9—C8 | 118.8 (3) | C11—C12—H15 | 109.30 |
O1—C10—N2 | 122.1 (3) | C11—C12—H16 | 109.39 |
O1—C10—C2 | 121.4 (3) | H14—C12—H15 | 109.53 |
N2—C10—C2 | 116.4 (3) | H14—C12—H16 | 109.41 |
O4—C11—C12 | 108.9 (3) | H15—C12—H16 | 110.22 |
P1—C13—C14 | 122.5 (2) | C13—C14—H17 | 125 (2) |
P1—C13—C18 | 118.9 (3) | C15—C14—H17 | 113 (2) |
C14—C13—C18 | 118.5 (3) | C14—C15—H18 | 121 (2) |
C13—C14—C15 | 122.0 (3) | C16—C15—H18 | 121 (2) |
C14—C15—C16 | 118.5 (4) | C16—C17—H19 | 123 (2) |
O5—C16—C15 | 124.4 (4) | C18—C17—H19 | 115 (2) |
O5—C16—C17 | 115.2 (4) | C13—C18—H20 | 120 (2) |
C15—C16—C17 | 120.4 (3) | C17—C18—H20 | 120 (2) |
C16—C17—C18 | 120.7 (4) | O5—C19—H21 | 109.79 |
C13—C18—C17 | 119.8 (4) | O5—C19—H22 | 109.37 |
N2—O2—H11 | 114 (3) | O5—C19—H23 | 109.89 |
O2—N2—H10 | 108 (2) | H21—C19—H22 | 109.06 |
C10—N2—H10 | 130 (2) | H21—C19—H23 | 109.74 |
N1—C1—H1 | 111 (2) | H22—C19—H23 | 108.98 |
| | | |
P1—O4—C11—C12 | 169.1 (3) | C1—N1—P1—C13 | 161.4 (2) |
P1—N1—C1—C8 | 139.4 (3) | C1—N1—C2—C3 | 51.0 (3) |
P1—N1—C2—C3 | −106.0 (3) | C1—N1—C2—C10 | −75.9 (3) |
P1—N1—C2—C10 | 127.2 (2) | C1—C8—C7—C6 | 178.3 (3) |
P1—C13—C14—C15 | 175.7 (3) | C1—C8—C9—C3 | 2.5 (5) |
P1—C13—C18—C17 | −176.5 (3) | C1—C8—C9—C4 | −178.9 (3) |
O1—C10—N2—O2 | 3.4 (5) | C2—N1—P1—C13 | −42.0 (3) |
O1—C10—C2—N1 | 162.6 (3) | C2—N1—C1—C8 | −18.3 (4) |
O1—C10—C2—C3 | 36.4 (4) | C2—C3—C9—C4 | −148.8 (3) |
O2—N2—C10—C2 | −173.2 (3) | C2—C3—C9—C8 | 29.7 (4) |
O3—P1—O4—C11 | 47.2 (3) | C3—C9—C4—C5 | 179.4 (3) |
O3—P1—N1—C1 | 35.3 (3) | C3—C9—C8—C7 | −178.1 (3) |
O3—P1—N1—C2 | −168.1 (2) | C4—C5—C6—C7 | 0.9 (6) |
O3—P1—C13—C14 | −133.6 (3) | C4—C9—C8—C7 | 0.5 (5) |
O3—P1—C13—C18 | 42.3 (3) | C5—C4—C9—C8 | 0.8 (5) |
O4—P1—N1—C1 | −86.8 (2) | C5—C6—C7—C8 | 0.5 (6) |
O4—P1—N1—C2 | 69.9 (2) | C6—C5—C4—C9 | −1.5 (6) |
O4—P1—C13—C14 | −9.5 (3) | C6—C7—C8—C9 | −1.2 (5) |
O4—P1—C13—C18 | 166.3 (3) | C9—C3—C2—C10 | 71.1 (3) |
O5—C16—C15—C14 | 179.7 (4) | C11—O4—P1—C13 | −77.7 (3) |
O5—C16—C17—C18 | 179.4 (4) | C13—C14—C15—C16 | −0.3 (5) |
N1—P1—O4—C11 | 168.7 (3) | C13—C18—C17—C16 | 1.6 (7) |
N1—P1—C13—C14 | 101.8 (3) | C14—C13—C18—C17 | −0.5 (6) |
N1—P1—C13—C18 | −82.4 (3) | C14—C15—C16—C17 | 1.4 (6) |
N1—C1—C8—C7 | 171.1 (3) | C15—C14—C13—C18 | −0.1 (5) |
N1—C1—C8—C9 | −9.5 (4) | C15—C16—O5—C19 | 10.3 (6) |
N1—C2—C3—C9 | −55.4 (3) | C15—C16—C17—C18 | −2.1 (6) |
N1—C2—C10—N2 | −20.8 (4) | C17—C16—O5—C19 | −171.3 (4) |
N2—C10—C2—C3 | −147.0 (3) | | |
Symmetry codes: (i) x−1/2, −y−1/2, −z−1; (ii) x, y, z+1; (iii) x+1/2, −y−1/2, −z−1; (iv) x+1/2, −y−1/2, −z−2; (v) −x−3/2, −y, z−1/2; (vi) −x−1, y−1/2, −z−3/2. |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H11···O1 | 0.90 (4) | 2.44 (3) | 2.701 (2) | 97 (2) |
N2—H10···N1 | 0.88 (3) | 2.46 (2) | 2.703 (2) | 96 (1) |
N2—H10···O1vii | 0.88 (3) | 2.12 (2) | 2.951 (2) | 158 (2) |
Symmetry code: (vii) x+1/2, −y+3/2, −z+1. |
Experimental details
Crystal data |
Chemical formula | C19H23N2O5P |
Mr | 390.37 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 294 |
a, b, c (Å) | 10.156 (2), 19.733 (1), 9.486 (1) |
V (Å3) | 1901.1 (3) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 1.57 |
Crystal size (mm) | 0.20 × 0.10 × 0.10 |
|
Data collection |
Diffractometer | Rigaku AFC-5R diffractometer |
Absorption correction | ψ scan (North et al., 1968) |
Tmin, Tmax | 0.757, 0.854 |
No. of measured, independent and observed [F2 > 2σ(F2)] reflections | 3303, 3303, 2991 |
Rint | 0.016 |
θmax (°) | 62.0 |
(sin θ/λ)max (Å−1) | 0.573 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.041, 0.102, 1.65 |
No. of reflections | 3303 |
No. of parameters | 313 |
No. of restraints | ? |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.17, −0.20 |
Absolute structure | Flack (1983), 1571 Friedel pairs |
Absolute structure parameter | 0.01 (3) |
Selected geometric parameters (Å, º) topP1—O3 | 1.477 (2) | P1—N1 | 1.636 (3) |
P1—O4 | 1.584 (2) | P1—C13 | 1.793 (3) |
| | | |
O3—P1—O4 | 112.6 (1) | O4—P1—N1 | 104.5 (1) |
O3—P1—N1 | 111.7 (1) | O4—P1—C13 | 105.5 (1) |
O3—P1—C13 | 114.0 (1) | N1—P1—C13 | 107.9 (1) |
| | | |
N1—C1—C8—C9 | −9.5 (4) | C2—C3—C9—C8 | 29.7 (4) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H11···O1 | 0.90 (4) | 2.44 (3) | 2.701 (2) | 97 (2) |
N2—H10···N1 | 0.88 (3) | 2.46 (2) | 2.703 (2) | 96 (1) |
N2—H10···O1i | 0.88 (3) | 2.12 (2) | 2.951 (2) | 158 (2) |
Symmetry code: (i) x+1/2, −y+3/2, −z+1. |
Subscribe to Acta Crystallographica Section E: Crystallographic Communications
The full text of this article is available to subscribers to the journal.
If you have already registered and are using a computer listed in your registration details, please email
support@iucr.org for assistance.
Matrix metalloproteinases (MMPs) are a family of zinc–metalloproteinases involved in the extracellular matrix degradation (Woessner, 1991). So far, more than 20 MMPs have been isolated and they are implicated in the pathological processes of a variety diseases associated with excessive degradation of the extracellular matrix, such as tumor metastasis (Yip et al., 1999), rheumatoid arthritis and osteoarthritis (Clark et al., 2000), multiple sclerosis (Gijbels et al., 1994). Therefore, a number of laboratories have energetically conducted the development of MMP inhibitors for the curatives of the diseases (Whittaker et al., 1999).
Recently, our group has reported that a phosphonamide-based hydroxamate showed potent inhibitory activities against MMP-1, -3, -9 (Sawa et al., 2001). It was found that one of the two diastereomers derived from the chirality at the P atom only showed potent inhibition against MMPs [active isomer: (II)], while the another isomer was inactive [inactive isomer: (I)]. This result suggested that the stereochemistry at the P atom was very important for the inhibition of the enzymes. Therefore, the establishment of the absolute configuration of the P atom would be a great help to study the interactions of the inhibitor in the active sites of MMPs. Moreover, it seems to be worthwhile information for the design of protease inhibitors. The inactive isomer (I) was used to X-ray analysis instead of the active isomer (II), because (I) could be much easily crystallized than (II).
As shown in Fig. 1, the configuration of the P atom of the inactive isomer (I) was determined to be S. The configuration of one of the two chiral centers, the α-carbon of the hydroxamate group was already known, because both (I) and (II) were synthesized from the known R-form of the starting material. The obtained configuration of the α-carbon, C2 is consistent with this stereochemistry (R configuration). Hence, the P atom of the active isomer (II) is in THE R configuration. Recently, Pikul et al. (1999) reported that a phosphinamide-based hydroxamate (III) having AN R configuration at the P atom exhibited inhibitory activities against MMPs, while the S isomer at the P atom was a poor inhibitor. As expected, the stereochemistry of the P atom of (II) was consistent with that of (III).
The structural data of (I) reveals that the non-aromatic portion in the tetrahydroisoquinoline unit adopts a half-chair conformation. The torsion angles C2—C3—C9—C8 and N1—C1—C8—C9 are 29.7 (4) and -9.5 (4)°, respectively. Comparison of the phosphonamide portion of (I) with the corresponding phosphinamide portion of (III) reveals that the structural differences as follows: The bond lengths around the P atom of (I), P1—O3, P1—N1 and P1—C13 are similar to the corresponding bond lengths of (III) in the range of 0.02 Å. On the other hand, the bond angles around the P atom of (I) are different from those of (III). The O3—P1—C13 bond angle of (I) is larger than the corresponding bond angle of (III) [114.0 (1) and 108.3°, respectively], whereas the O4—P1—C13 and N1—P1—C13 bond angles are smaller than those of (III) [O4—P1—C13 105.5 (1)° for (I) and 108.3° for (III); N1—P1—C13 107.9 (1)° for (I) and 110.5° for (III)]. Namely, P1—C13 bond of (I) leans to the N1—P1—O4 plane compared to that of (III).