Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807038391/zl2036sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807038391/zl2036Isup2.hkl |
CCDC reference: 660237
Key indicators
- Single-crystal X-ray study
- T = 223 K
- Mean (C-C) = 0.003 Å
- R factor = 0.039
- wR factor = 0.087
- Data-to-parameter ratio = 14.2
checkCIF/PLATON results
No syntax errors found
Alert level C ABSTM02_ALERT_3_C The ratio of expected to reported Tmax/Tmin(RR') is < 0.90 Tmin and Tmax reported: 0.720 0.948 Tmin(prime) and Tmax expected: 0.914 0.948 RR(prime) = 0.788 Please check that your absorption correction is appropriate. PLAT061_ALERT_3_C Tmax/Tmin Range Test RR' too Large ............. 0.79 PLAT411_ALERT_2_C Short Inter H...H Contact H12 .. H29 .. 2.13 Ang.
Alert level G REFLT03_ALERT_4_G 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. From the CIF: _diffrn_reflns_theta_max 25.34 From the CIF: _reflns_number_total 4678 Count of symmetry unique reflns 2622 Completeness (_total/calc) 178.41% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 2056 Fraction of Friedel pairs measured 0.784 Are heavy atom types Z>Si present yes PLAT791_ALERT_1_G Confirm the Absolute Configuration of C1 = . S PLAT791_ALERT_1_G Confirm the Absolute Configuration of C2 = . S PLAT791_ALERT_1_G Confirm the Absolute Configuration of C3 = . S PLAT791_ALERT_1_G Confirm the Absolute Configuration of C12 = . S PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints ....... 1
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 3 ALERT level C = Check and explain 6 ALERT level G = General alerts; check 4 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 1 ALERT type 2 Indicator that the structure model may be wrong or deficient 3 ALERT type 3 Indicator that the structure quality may be low 1 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check
For related literature, see: Casanovas et al. (2003); Huang et al. (2007); Jiménez et al. (2005); Royo et al. (2005); Su et al. (2003).
0.83 g (2.12 mmol) of 1-benzoylamino-2-(4-chloro-phenyl)-3-phenyl- cyclopropanecarboxylic acid (1), obtained by treatment of 1-benzoylamino-2-(4-chloro-phenyl)-3-phenyl-cyclopropanecarboxylic acid methyl ester with a solution of 2 M potassium hydroxide in anhydrous methanol (Su et al., 2003, Huang et al., 2007), was coupled with 2-amino-3-methyl-butyric acid methyl ester hydrochloride (0.36 g, 2.12 mmol) at 254 K by the classic mixed anhydride method using isobutyl chloroformate as the coupling agent. Then the resulting mixture of diastereoisomers (2 and 3 in Figure 3) (0.65 g, white solid) was aminolyzed in a 9.8 M methanolic solution of MeNH2 (15 ml). A careful column chromatography on silica gel (eluent: CHCl3/AcOEt 5:3, v/v) affords the corresponding enantiomerically pure dipeptides PhCO-(2S,3S)-c3diAr-Val-NHCH3 (4) and PhCO-(2R,3R)-c3diAr-Val-NHCH3 (5) in 36% and 26% yield respectively (Fig. 3). Recrystallization from CH2Cl2/CH3OH (5:1 v/v) afforded colourless crystals (m.p. 516–517 K) of PhCO-(2S,3S)-c3diAr-Val-NHCH3 (4).
The H atoms bound to C atoms were positioned geometrically and included in the refinement in the riding-model approximation, with C—H = 0.94–0.99 Å and with Uiso(H) = 1.5Ueq(C) for methyl and 1.2Ueq(C) for all other H atoms.
The synthesis of conformationally restricted model peptides has become one of the research foci in bioorganic and medicinal chemistry in recent years. One common strategy in the design of conformationally restricted model peptides is to incorporate conformationally restricted amino acids into peptide chains to reduce the degrees of freedom of the peptide, which will greatly enhance their selectivity to the receptor, a prerequisite for their successful use as biologically active compounds (Jiménez et al., 2005; Royo et al., 2005; Casanovas et al., 2003).
The title compound (I) (PhCO-c3diAr-Val-NHCH3) is a conformationally restricted model dipeptide. The absolute configuration of the c3diAr residue was established as (2S,3S) (Fig.1). The two substituents of the phenyl and p-chloro-phenyl on the three-membered ring are in a trans arrangement. The rigidity of the three-membered ring fixes the side chain in a well defined orientation and this disposition is different for each stereoisomer. There is a compromise between the inflexible molecule and its desire to form strong N—H···O hydrogen bonds that leads to a very short H···H contact of 2.134 (1) Angstrom (H29···H12). The crystal packing is stabilized by several N—H···O hydrogen bonds and there are also a several relatively short intermolecular C—H···O hydrogen bonds (Table 1). All these interactions link the molecules into one-dimensional chains and are attributable to stabilize the structure (Fig. 2).
For related literature, see: Casanovas et al. (2003); Huang et al. (2007); Jiménez et al. (2005); Royo et al. (2005); Su et al. (2003).
Data collection: CrystalClear (Rigaku/MSC, 2000); cell refinement: CrystalClear; data reduction: CrystalStructure (Rigaku, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 2000); software used to prepare material for publication: SHELXTL.
C29H30ClN3O3 | F(000) = 532 |
Mr = 504.01 | Dx = 1.247 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71070 Å |
Hall symbol: P 2yb | Cell parameters from 5213 reflections |
a = 10.8821 (19) Å | θ = 3.2–25.3° |
b = 9.5688 (16) Å | µ = 0.18 mm−1 |
c = 12.952 (2) Å | T = 223 K |
β = 95.754 (4)° | Block, colourless |
V = 1341.9 (4) Å3 | 0.50 × 0.36 × 0.30 mm |
Z = 2 |
Rigaku Mercury diffractometer | 4678 independent reflections |
Radiation source: fine-focus sealed tube | 4334 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.028 |
Detector resolution: 7.31 pixels mm-1 | θmax = 25.3°, θmin = 3.2° |
ω scans | h = −12→13 |
Absorption correction: multi-scan (Jacobson, 1998) | k = −11→11 |
Tmin = 0.720, Tmax = 0.948 | l = −15→15 |
13162 measured reflections |
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)] = 0.039 | H-atom parameters constrained |
wR(F2) = 0.087 | w = 1/[σ2(Fo2) + (0.0394P)2 + 0.1618P] where P = (Fo2 + 2Fc2)/3 |
S = 1.09 | (Δ/σ)max < 0.001 |
4678 reflections | Δρmax = 0.13 e Å−3 |
329 parameters | Δρmin = −0.19 e Å−3 |
1 restraint | Absolute structure: Flack (1983), with 2067 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.03 (7) |
C29H30ClN3O3 | V = 1341.9 (4) Å3 |
Mr = 504.01 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 10.8821 (19) Å | µ = 0.18 mm−1 |
b = 9.5688 (16) Å | T = 223 K |
c = 12.952 (2) Å | 0.50 × 0.36 × 0.30 mm |
β = 95.754 (4)° |
Rigaku Mercury diffractometer | 4678 independent reflections |
Absorption correction: multi-scan (Jacobson, 1998) | 4334 reflections with I > 2σ(I) |
Tmin = 0.720, Tmax = 0.948 | Rint = 0.028 |
13162 measured reflections |
R[F2 > 2σ(F2)] = 0.039 | H-atom parameters constrained |
wR(F2) = 0.087 | Δρmax = 0.13 e Å−3 |
S = 1.09 | Δρmin = −0.19 e Å−3 |
4678 reflections | Absolute structure: Flack (1983), with 2067 Friedel pairs |
329 parameters | Absolute structure parameter: 0.03 (7) |
1 restraint |
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 | ||
Cl1 | −0.04548 (6) | 0.93271 (10) | 0.97899 (5) | 0.0693 (2) | |
O1 | 0.51546 (14) | 0.93017 (16) | 0.76039 (11) | 0.0401 (4) | |
O2 | 0.44949 (13) | 1.03295 (14) | 0.51521 (12) | 0.0343 (3) | |
O3 | 0.69537 (14) | 0.97648 (15) | 0.32163 (12) | 0.0387 (4) | |
N1 | 0.40924 (14) | 0.75020 (17) | 0.68410 (12) | 0.0281 (4) | |
H1 | 0.3900 | 0.6620 | 0.6849 | 0.034* | |
N2 | 0.55739 (14) | 0.83074 (16) | 0.53124 (13) | 0.0276 (4) | |
H2 | 0.5547 | 0.7427 | 0.5478 | 0.033* | |
N3 | 0.61830 (17) | 0.75935 (18) | 0.32730 (13) | 0.0367 (4) | |
H3 | 0.5969 | 0.6912 | 0.3662 | 0.044* | |
C1 | 0.36200 (17) | 0.83804 (19) | 0.59967 (15) | 0.0271 (4) | |
C2 | 0.23957 (17) | 0.9144 (2) | 0.60451 (15) | 0.0308 (4) | |
H2B | 0.2357 | 1.0055 | 0.5681 | 0.037* | |
C3 | 0.24678 (18) | 0.7912 (2) | 0.53285 (15) | 0.0297 (4) | |
H3B | 0.2090 | 0.7044 | 0.5568 | 0.036* | |
C4 | 0.48463 (19) | 0.8075 (2) | 0.76281 (16) | 0.0319 (5) | |
C5 | 0.5331 (2) | 0.7109 (2) | 0.84811 (15) | 0.0344 (5) | |
C6 | 0.6533 (2) | 0.7319 (3) | 0.89339 (17) | 0.0434 (6) | |
H6 | 0.7002 | 0.8065 | 0.8710 | 0.052* | |
C7 | 0.7041 (3) | 0.6441 (3) | 0.97087 (19) | 0.0553 (7) | |
H7 | 0.7860 | 0.6574 | 0.9996 | 0.066* | |
C8 | 0.6352 (3) | 0.5375 (3) | 1.00590 (19) | 0.0567 (7) | |
H8 | 0.6701 | 0.4773 | 1.0582 | 0.068* | |
C9 | 0.5153 (3) | 0.5188 (3) | 0.9647 (2) | 0.0634 (8) | |
H9 | 0.4671 | 0.4477 | 0.9905 | 0.076* | |
C10 | 0.4646 (3) | 0.6050 (3) | 0.88447 (18) | 0.0510 (7) | |
H10 | 0.3831 | 0.5903 | 0.8553 | 0.061* | |
C11 | 0.46021 (17) | 0.9113 (2) | 0.54537 (14) | 0.0265 (4) | |
C12 | 0.66756 (17) | 0.8836 (2) | 0.48946 (15) | 0.0290 (4) | |
H12 | 0.6767 | 0.9831 | 0.5097 | 0.035* | |
C13 | 0.65934 (18) | 0.8770 (2) | 0.37172 (16) | 0.0308 (5) | |
C14 | 0.6078 (3) | 0.7401 (3) | 0.21541 (17) | 0.0482 (6) | |
H14A | 0.5414 | 0.7981 | 0.1835 | 0.072* | |
H14B | 0.5901 | 0.6428 | 0.1990 | 0.072* | |
H14C | 0.6848 | 0.7667 | 0.1890 | 0.072* | |
C15 | 0.78250 (18) | 0.8054 (2) | 0.53901 (17) | 0.0370 (5) | |
H15 | 0.7725 | 0.7052 | 0.5213 | 0.044* | |
C16 | 0.7953 (2) | 0.8184 (3) | 0.65662 (19) | 0.0559 (7) | |
H16A | 0.8710 | 0.7732 | 0.6851 | 0.084* | |
H16B | 0.7253 | 0.7740 | 0.6840 | 0.084* | |
H16C | 0.7978 | 0.9165 | 0.6758 | 0.084* | |
C17 | 0.8986 (2) | 0.8572 (4) | 0.4957 (2) | 0.0622 (8) | |
H17A | 0.8876 | 0.8524 | 0.4205 | 0.093* | |
H17B | 0.9680 | 0.7992 | 0.5216 | 0.093* | |
H17C | 0.9144 | 0.9532 | 0.5171 | 0.093* | |
C18 | 0.16989 (17) | 0.9123 (2) | 0.69795 (15) | 0.0325 (5) | |
C19 | 0.1195 (2) | 1.0362 (2) | 0.72906 (18) | 0.0394 (5) | |
H19 | 0.1309 | 1.1181 | 0.6910 | 0.047* | |
C20 | 0.0527 (2) | 1.0435 (3) | 0.81444 (19) | 0.0465 (6) | |
H20 | 0.0181 | 1.1286 | 0.8335 | 0.056* | |
C21 | 0.03798 (19) | 0.9244 (3) | 0.87064 (16) | 0.0435 (5) | |
C22 | 0.0854 (2) | 0.7992 (3) | 0.84255 (18) | 0.0434 (6) | |
H22 | 0.0742 | 0.7183 | 0.8817 | 0.052* | |
C23 | 0.1505 (2) | 0.7927 (2) | 0.75545 (17) | 0.0381 (5) | |
H23 | 0.1817 | 0.7064 | 0.7352 | 0.046* | |
C24 | 0.23451 (18) | 0.8098 (2) | 0.41708 (16) | 0.0308 (4) | |
C25 | 0.1599 (2) | 0.9128 (3) | 0.36832 (17) | 0.0420 (5) | |
H25 | 0.1180 | 0.9754 | 0.4084 | 0.050* | |
C26 | 0.1466 (2) | 0.9245 (3) | 0.26140 (19) | 0.0556 (7) | |
H26 | 0.0961 | 0.9951 | 0.2295 | 0.067* | |
C27 | 0.2066 (2) | 0.8335 (3) | 0.20145 (19) | 0.0543 (7) | |
H27 | 0.1963 | 0.8411 | 0.1287 | 0.065* | |
C28 | 0.2814 (2) | 0.7317 (3) | 0.24767 (17) | 0.0473 (6) | |
H28 | 0.3229 | 0.6696 | 0.2068 | 0.057* | |
C29 | 0.2959 (2) | 0.7204 (2) | 0.35476 (16) | 0.0378 (5) | |
H29 | 0.3483 | 0.6510 | 0.3860 | 0.045* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0616 (4) | 0.1030 (6) | 0.0466 (4) | −0.0071 (4) | 0.0225 (3) | −0.0152 (4) |
O1 | 0.0530 (9) | 0.0268 (8) | 0.0392 (8) | −0.0032 (7) | −0.0017 (7) | −0.0039 (7) |
O2 | 0.0374 (8) | 0.0221 (8) | 0.0439 (9) | 0.0009 (6) | 0.0059 (7) | 0.0054 (6) |
O3 | 0.0479 (9) | 0.0266 (8) | 0.0430 (9) | −0.0031 (7) | 0.0117 (7) | 0.0034 (6) |
N1 | 0.0325 (9) | 0.0230 (9) | 0.0283 (9) | −0.0006 (7) | 0.0012 (7) | 0.0025 (7) |
N2 | 0.0297 (8) | 0.0196 (8) | 0.0342 (9) | 0.0003 (7) | 0.0072 (7) | 0.0005 (7) |
N3 | 0.0503 (11) | 0.0292 (10) | 0.0313 (9) | −0.0060 (8) | 0.0071 (8) | −0.0007 (8) |
C1 | 0.0307 (10) | 0.0229 (10) | 0.0277 (10) | 0.0016 (8) | 0.0024 (8) | 0.0013 (8) |
C2 | 0.0285 (10) | 0.0289 (11) | 0.0349 (11) | 0.0023 (9) | 0.0031 (8) | 0.0039 (9) |
C3 | 0.0278 (10) | 0.0295 (11) | 0.0314 (11) | −0.0040 (8) | 0.0020 (8) | 0.0028 (9) |
C4 | 0.0355 (11) | 0.0307 (12) | 0.0298 (11) | 0.0021 (9) | 0.0052 (9) | −0.0040 (9) |
C5 | 0.0473 (13) | 0.0316 (11) | 0.0241 (10) | 0.0022 (10) | 0.0027 (9) | −0.0018 (9) |
C6 | 0.0494 (14) | 0.0499 (14) | 0.0302 (12) | 0.0028 (11) | 0.0000 (10) | −0.0003 (11) |
C7 | 0.0597 (16) | 0.073 (2) | 0.0304 (13) | 0.0187 (15) | −0.0062 (12) | 0.0018 (12) |
C8 | 0.085 (2) | 0.0533 (16) | 0.0292 (12) | 0.0142 (15) | −0.0068 (13) | 0.0020 (12) |
C9 | 0.099 (2) | 0.0501 (16) | 0.0384 (14) | −0.0173 (15) | −0.0051 (15) | 0.0113 (12) |
C10 | 0.0643 (17) | 0.0509 (15) | 0.0352 (13) | −0.0126 (13) | −0.0084 (12) | 0.0073 (12) |
C11 | 0.0285 (10) | 0.0242 (11) | 0.0260 (10) | −0.0022 (8) | −0.0010 (8) | −0.0018 (8) |
C12 | 0.0283 (10) | 0.0241 (10) | 0.0352 (11) | −0.0021 (8) | 0.0059 (9) | −0.0019 (8) |
C13 | 0.0280 (10) | 0.0271 (11) | 0.0377 (11) | 0.0024 (8) | 0.0061 (9) | −0.0017 (9) |
C14 | 0.0708 (16) | 0.0410 (14) | 0.0331 (12) | −0.0061 (13) | 0.0069 (11) | −0.0040 (10) |
C15 | 0.0301 (10) | 0.0408 (13) | 0.0397 (12) | 0.0033 (9) | 0.0007 (9) | −0.0066 (10) |
C16 | 0.0470 (14) | 0.076 (2) | 0.0427 (14) | 0.0094 (14) | −0.0037 (11) | 0.0017 (13) |
C17 | 0.0314 (12) | 0.093 (2) | 0.0618 (17) | −0.0015 (13) | 0.0043 (12) | 0.0001 (16) |
C18 | 0.0247 (9) | 0.0368 (12) | 0.0353 (11) | −0.0014 (9) | 0.0000 (8) | 0.0008 (10) |
C19 | 0.0376 (12) | 0.0381 (12) | 0.0424 (13) | 0.0015 (10) | 0.0041 (10) | −0.0028 (10) |
C20 | 0.0414 (13) | 0.0520 (15) | 0.0464 (14) | 0.0052 (12) | 0.0053 (11) | −0.0135 (12) |
C21 | 0.0331 (11) | 0.0657 (16) | 0.0318 (11) | −0.0050 (12) | 0.0044 (9) | −0.0103 (12) |
C22 | 0.0380 (12) | 0.0546 (15) | 0.0380 (13) | −0.0050 (11) | 0.0064 (10) | 0.0074 (11) |
C23 | 0.0353 (11) | 0.0380 (13) | 0.0413 (12) | 0.0009 (10) | 0.0057 (10) | 0.0020 (10) |
C24 | 0.0275 (10) | 0.0315 (11) | 0.0329 (11) | −0.0064 (9) | 0.0013 (8) | 0.0056 (9) |
C25 | 0.0404 (12) | 0.0446 (14) | 0.0397 (12) | 0.0048 (11) | −0.0023 (10) | 0.0077 (11) |
C26 | 0.0577 (15) | 0.0586 (16) | 0.0473 (14) | 0.0079 (14) | −0.0106 (12) | 0.0181 (14) |
C27 | 0.0585 (15) | 0.0732 (19) | 0.0300 (12) | −0.0068 (15) | −0.0016 (11) | 0.0097 (12) |
C28 | 0.0528 (14) | 0.0550 (15) | 0.0344 (13) | −0.0027 (13) | 0.0059 (11) | 0.0005 (11) |
C29 | 0.0398 (12) | 0.0373 (12) | 0.0357 (12) | −0.0004 (10) | 0.0008 (10) | 0.0030 (10) |
Cl1—C21 | 1.748 (2) | C12—H12 | 0.9900 |
O1—C4 | 1.222 (3) | C14—H14A | 0.9700 |
O2—C11 | 1.230 (2) | C14—H14B | 0.9700 |
O3—C13 | 1.238 (2) | C14—H14C | 0.9700 |
N1—C4 | 1.358 (3) | C15—C17 | 1.516 (3) |
N1—C1 | 1.433 (2) | C15—C16 | 1.521 (3) |
N1—H1 | 0.8700 | C15—H15 | 0.9900 |
N2—C11 | 1.336 (2) | C16—H16A | 0.9700 |
N2—C12 | 1.455 (2) | C16—H16B | 0.9700 |
N2—H2 | 0.8700 | C16—H16C | 0.9700 |
N3—C13 | 1.321 (3) | C17—H17A | 0.9700 |
N3—C14 | 1.454 (3) | C17—H17B | 0.9700 |
N3—H3 | 0.8700 | C17—H17C | 0.9700 |
C1—C11 | 1.510 (3) | C18—C19 | 1.384 (3) |
C1—C3 | 1.518 (3) | C18—C23 | 1.393 (3) |
C1—C2 | 1.526 (3) | C19—C20 | 1.385 (3) |
C2—C18 | 1.491 (3) | C19—H19 | 0.9400 |
C2—C3 | 1.507 (3) | C20—C21 | 1.370 (4) |
C2—H2B | 0.9900 | C20—H20 | 0.9400 |
C3—C24 | 1.503 (3) | C21—C22 | 1.369 (4) |
C3—H3B | 0.9900 | C22—C23 | 1.392 (3) |
C4—C5 | 1.496 (3) | C22—H22 | 0.9400 |
C5—C10 | 1.369 (3) | C23—H23 | 0.9400 |
C5—C6 | 1.393 (3) | C24—C25 | 1.389 (3) |
C6—C7 | 1.381 (3) | C24—C29 | 1.392 (3) |
C6—H6 | 0.9400 | C25—C26 | 1.382 (3) |
C7—C8 | 1.369 (4) | C25—H25 | 0.9400 |
C7—H7 | 0.9400 | C26—C27 | 1.375 (4) |
C8—C9 | 1.371 (4) | C26—H26 | 0.9400 |
C8—H8 | 0.9400 | C27—C28 | 1.368 (4) |
C9—C10 | 1.396 (3) | C27—H27 | 0.9400 |
C9—H9 | 0.9400 | C28—C29 | 1.384 (3) |
C10—H10 | 0.9400 | C28—H28 | 0.9400 |
C12—C13 | 1.520 (3) | C29—H29 | 0.9400 |
C12—C15 | 1.541 (3) | ||
C4—N1—C1 | 118.66 (16) | N3—C14—H14A | 109.5 |
C4—N1—H1 | 120.7 | N3—C14—H14B | 109.5 |
C1—N1—H1 | 120.7 | H14A—C14—H14B | 109.5 |
C11—N2—C12 | 122.92 (16) | N3—C14—H14C | 109.5 |
C11—N2—H2 | 118.5 | H14A—C14—H14C | 109.5 |
C12—N2—H2 | 118.5 | H14B—C14—H14C | 109.5 |
C13—N3—C14 | 122.09 (19) | C17—C15—C16 | 110.4 (2) |
C13—N3—H3 | 119.0 | C17—C15—C12 | 111.0 (2) |
C14—N3—H3 | 119.0 | C16—C15—C12 | 111.50 (18) |
N1—C1—C11 | 114.29 (16) | C17—C15—H15 | 107.9 |
N1—C1—C3 | 118.32 (16) | C16—C15—H15 | 107.9 |
C11—C1—C3 | 117.03 (16) | C12—C15—H15 | 107.9 |
N1—C1—C2 | 119.81 (16) | C15—C16—H16A | 109.5 |
C11—C1—C2 | 117.30 (16) | C15—C16—H16B | 109.5 |
C3—C1—C2 | 59.35 (13) | H16A—C16—H16B | 109.5 |
C18—C2—C3 | 123.47 (18) | C15—C16—H16C | 109.5 |
C18—C2—C1 | 122.95 (17) | H16A—C16—H16C | 109.5 |
C3—C2—C1 | 60.06 (13) | H16B—C16—H16C | 109.5 |
C18—C2—H2B | 113.4 | C15—C17—H17A | 109.5 |
C3—C2—H2B | 113.4 | C15—C17—H17B | 109.5 |
C1—C2—H2B | 113.4 | H17A—C17—H17B | 109.5 |
C24—C3—C2 | 121.14 (18) | C15—C17—H17C | 109.5 |
C24—C3—C1 | 121.31 (17) | H17A—C17—H17C | 109.5 |
C2—C3—C1 | 60.59 (13) | H17B—C17—H17C | 109.5 |
C24—C3—H3B | 114.5 | C19—C18—C23 | 117.56 (19) |
C2—C3—H3B | 114.5 | C19—C18—C2 | 118.3 (2) |
C1—C3—H3B | 114.5 | C23—C18—C2 | 124.2 (2) |
O1—C4—N1 | 120.99 (19) | C18—C19—C20 | 122.1 (2) |
O1—C4—C5 | 122.35 (19) | C18—C19—H19 | 119.0 |
N1—C4—C5 | 116.56 (18) | C20—C19—H19 | 119.0 |
C10—C5—C6 | 118.9 (2) | C21—C20—C19 | 118.7 (2) |
C10—C5—C4 | 123.2 (2) | C21—C20—H20 | 120.6 |
C6—C5—C4 | 117.9 (2) | C19—C20—H20 | 120.6 |
C7—C6—C5 | 120.5 (2) | C22—C21—C20 | 121.3 (2) |
C7—C6—H6 | 119.7 | C22—C21—Cl1 | 119.6 (2) |
C5—C6—H6 | 119.7 | C20—C21—Cl1 | 119.1 (2) |
C8—C7—C6 | 120.1 (3) | C21—C22—C23 | 119.4 (2) |
C8—C7—H7 | 119.9 | C21—C22—H22 | 120.3 |
C6—C7—H7 | 119.9 | C23—C22—H22 | 120.3 |
C7—C8—C9 | 120.0 (2) | C22—C23—C18 | 120.9 (2) |
C7—C8—H8 | 120.0 | C22—C23—H23 | 119.6 |
C9—C8—H8 | 120.0 | C18—C23—H23 | 119.6 |
C8—C9—C10 | 120.1 (3) | C25—C24—C29 | 117.74 (19) |
C8—C9—H9 | 119.9 | C25—C24—C3 | 121.83 (19) |
C10—C9—H9 | 119.9 | C29—C24—C3 | 120.41 (18) |
C5—C10—C9 | 120.4 (2) | C26—C25—C24 | 120.7 (2) |
C5—C10—H10 | 119.8 | C26—C25—H25 | 119.6 |
C9—C10—H10 | 119.8 | C24—C25—H25 | 119.6 |
O2—C11—N2 | 123.64 (18) | C27—C26—C25 | 120.4 (2) |
O2—C11—C1 | 122.59 (18) | C27—C26—H26 | 119.8 |
N2—C11—C1 | 113.75 (16) | C25—C26—H26 | 119.8 |
N2—C12—C13 | 113.02 (16) | C28—C27—C26 | 120.0 (2) |
N2—C12—C15 | 109.95 (16) | C28—C27—H27 | 120.0 |
C13—C12—C15 | 111.18 (16) | C26—C27—H27 | 120.0 |
N2—C12—H12 | 107.5 | C27—C28—C29 | 119.8 (2) |
C13—C12—H12 | 107.5 | C27—C28—H28 | 120.1 |
C15—C12—H12 | 107.5 | C29—C28—H28 | 120.1 |
O3—C13—N3 | 122.54 (19) | C28—C29—C24 | 121.3 (2) |
O3—C13—C12 | 120.27 (18) | C28—C29—H29 | 119.3 |
N3—C13—C12 | 117.11 (18) | C24—C29—H29 | 119.3 |
C4—N1—C1—C11 | 56.8 (2) | C11—N2—C12—C13 | −88.6 (2) |
C4—N1—C1—C3 | −159.11 (18) | C11—N2—C12—C15 | 146.52 (18) |
C4—N1—C1—C2 | −90.1 (2) | C14—N3—C13—O3 | −2.5 (3) |
N1—C1—C2—C18 | 5.4 (3) | C14—N3—C13—C12 | −179.27 (19) |
C11—C1—C2—C18 | −140.58 (19) | N2—C12—C13—O3 | 137.01 (18) |
C3—C1—C2—C18 | 112.6 (2) | C15—C12—C13—O3 | −98.8 (2) |
N1—C1—C2—C3 | −107.22 (19) | N2—C12—C13—N3 | −46.2 (2) |
C11—C1—C2—C3 | 106.77 (19) | C15—C12—C13—N3 | 78.0 (2) |
C18—C2—C3—C24 | 137.30 (19) | N2—C12—C15—C17 | 179.2 (2) |
C1—C2—C3—C24 | −110.9 (2) | C13—C12—C15—C17 | 53.3 (2) |
C18—C2—C3—C1 | −111.8 (2) | N2—C12—C15—C16 | −57.2 (2) |
N1—C1—C3—C24 | −139.70 (19) | C13—C12—C15—C16 | 176.83 (19) |
C11—C1—C3—C24 | 3.4 (3) | C3—C2—C18—C19 | −149.82 (19) |
C2—C1—C3—C24 | 110.6 (2) | C1—C2—C18—C19 | 136.7 (2) |
N1—C1—C3—C2 | 109.70 (19) | C3—C2—C18—C23 | 29.1 (3) |
C11—C1—C3—C2 | −107.23 (19) | C1—C2—C18—C23 | −44.3 (3) |
C1—N1—C4—O1 | −2.6 (3) | C23—C18—C19—C20 | 0.5 (3) |
C1—N1—C4—C5 | −178.99 (17) | C2—C18—C19—C20 | 179.5 (2) |
O1—C4—C5—C10 | 146.1 (2) | C18—C19—C20—C21 | 1.1 (3) |
N1—C4—C5—C10 | −37.5 (3) | C19—C20—C21—C22 | −1.5 (3) |
O1—C4—C5—C6 | −32.8 (3) | C19—C20—C21—Cl1 | 179.66 (17) |
N1—C4—C5—C6 | 143.5 (2) | C20—C21—C22—C23 | 0.3 (3) |
C10—C5—C6—C7 | 2.5 (3) | Cl1—C21—C22—C23 | 179.18 (17) |
C4—C5—C6—C7 | −178.5 (2) | C21—C22—C23—C18 | 1.3 (3) |
C5—C6—C7—C8 | −1.8 (4) | C19—C18—C23—C22 | −1.7 (3) |
C6—C7—C8—C9 | −0.6 (4) | C2—C18—C23—C22 | 179.35 (19) |
C7—C8—C9—C10 | 2.3 (4) | C2—C3—C24—C25 | −32.7 (3) |
C6—C5—C10—C9 | −0.8 (4) | C1—C3—C24—C25 | −105.0 (2) |
C4—C5—C10—C9 | −179.7 (2) | C2—C3—C24—C29 | 149.11 (19) |
C8—C9—C10—C5 | −1.6 (4) | C1—C3—C24—C29 | 76.8 (3) |
C12—N2—C11—O2 | 7.5 (3) | C29—C24—C25—C26 | 0.7 (3) |
C12—N2—C11—C1 | −174.07 (16) | C3—C24—C25—C26 | −177.6 (2) |
N1—C1—C11—O2 | −140.36 (18) | C24—C25—C26—C27 | 0.4 (4) |
C3—C1—C11—O2 | 75.1 (2) | C25—C26—C27—C28 | −0.9 (4) |
C2—C1—C11—O2 | 7.5 (3) | C26—C27—C28—C29 | 0.3 (4) |
N1—C1—C11—N2 | 41.2 (2) | C27—C28—C29—C24 | 0.8 (3) |
C3—C1—C11—N2 | −103.4 (2) | C25—C24—C29—C28 | −1.3 (3) |
C2—C1—C11—N2 | −170.97 (16) | C3—C24—C29—C28 | 177.0 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O3i | 0.87 | 2.00 | 2.854 (2) | 166 |
N2—H2···O2i | 0.87 | 2.17 | 2.912 (2) | 144 |
N3—H3···O2i | 0.87 | 2.25 | 3.114 (2) | 173 |
C14—H14B···O1i | 0.97 | 2.42 | 3.283 (3) | 148 |
Symmetry code: (i) −x+1, y−1/2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C29H30ClN3O3 |
Mr | 504.01 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 223 |
a, b, c (Å) | 10.8821 (19), 9.5688 (16), 12.952 (2) |
β (°) | 95.754 (4) |
V (Å3) | 1341.9 (4) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.18 |
Crystal size (mm) | 0.50 × 0.36 × 0.30 |
Data collection | |
Diffractometer | Rigaku Mercury |
Absorption correction | Multi-scan (Jacobson, 1998) |
Tmin, Tmax | 0.720, 0.948 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 13162, 4678, 4334 |
Rint | 0.028 |
(sin θ/λ)max (Å−1) | 0.602 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.039, 0.087, 1.09 |
No. of reflections | 4678 |
No. of parameters | 329 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.13, −0.19 |
Absolute structure | Flack (1983), with 2067 Friedel pairs |
Absolute structure parameter | 0.03 (7) |
Computer programs: CrystalClear (Rigaku/MSC, 2000), CrystalClear, CrystalStructure (Rigaku, 1999), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Sheldrick, 2000), SHELXTL.
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O3i | 0.87 | 2.00 | 2.854 (2) | 166.2 |
N2—H2···O2i | 0.87 | 2.17 | 2.912 (2) | 143.6 |
N3—H3···O2i | 0.87 | 2.25 | 3.114 (2) | 172.5 |
C14—H14B···O1i | 0.97 | 2.42 | 3.283 (3) | 147.9 |
Symmetry code: (i) −x+1, y−1/2, −z+1. |
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The synthesis of conformationally restricted model peptides has become one of the research foci in bioorganic and medicinal chemistry in recent years. One common strategy in the design of conformationally restricted model peptides is to incorporate conformationally restricted amino acids into peptide chains to reduce the degrees of freedom of the peptide, which will greatly enhance their selectivity to the receptor, a prerequisite for their successful use as biologically active compounds (Jiménez et al., 2005; Royo et al., 2005; Casanovas et al., 2003).
The title compound (I) (PhCO-c3diAr-Val-NHCH3) is a conformationally restricted model dipeptide. The absolute configuration of the c3diAr residue was established as (2S,3S) (Fig.1). The two substituents of the phenyl and p-chloro-phenyl on the three-membered ring are in a trans arrangement. The rigidity of the three-membered ring fixes the side chain in a well defined orientation and this disposition is different for each stereoisomer. There is a compromise between the inflexible molecule and its desire to form strong N—H···O hydrogen bonds that leads to a very short H···H contact of 2.134 (1) Angstrom (H29···H12). The crystal packing is stabilized by several N—H···O hydrogen bonds and there are also a several relatively short intermolecular C—H···O hydrogen bonds (Table 1). All these interactions link the molecules into one-dimensional chains and are attributable to stabilize the structure (Fig. 2).