Asymmetric synthesis of tetrahydroisoquinoline-fused spirooxindoles as Ras-GTP inhibitors that inhibit colon adenocarcinoma cell proliferation and invasion.
Zhao, Qian; Peng, Cheng; Huang, Hua; Liu, Shuai-Jiang; Zhong, Ya-Jun; Huang, Wei; He, Gu; Han, Bo; Chemical communications (Cambridge, England) 54 (2018) 8359–8362; doi:10.1039/c8cc04732d

data_7121949
_publ_section_title
;
 Asymmetric synthesis of tetrahydroisoquinoline-fused spirooxindoles as
 Ras-GTP inhibitors that inhibit colon adenocarcinoma cell proliferation
 and invasion.
;
_journal_issue                   60
_journal_name_full               'Chemical communications (Cambridge, England)'
_journal_page_first              8359
_journal_page_last               8362
_journal_paper_doi               10.1039/c8cc04732d
_journal_volume                  54
_journal_year                    2018
_chemical_formula_moiety         'C29 H28 N4 O8, C4 H8 O2'
_chemical_formula_sum            'C33 H36 N4 O10'
_chemical_formula_weight         648.66
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2ybc'
_space_group_name_H-M_alt        'P 1 21/c 1'
_symmetry_space_group_name_Hall  '-P 2ybc'
_symmetry_space_group_name_H-M   'P 1 21/c 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_audit_creation_date             2018-04-18
_audit_creation_method
;
Olex2 1.2
(compiled 2017.08.10 svn.r3458 for OlexSys, GUI svn.r5381)
;
_audit_update_record
;
2018-06-10 deposited with the CCDC.
2018-07-04 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90.3385(17)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   10.4543(2)
_cell_length_b                   13.8322(3)
_cell_length_c                   23.1289(5)
_cell_measurement_reflns_used    5693
_cell_measurement_temperature    295.12(15)
_cell_measurement_theta_max      72.3620
_cell_measurement_theta_min      4.6090
_cell_volume                     3344.52(12)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_collection
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      air
_diffrn_ambient_temperature      295.12(15)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 7.9797
_diffrn_detector_type            EosS2
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.974
_diffrn_measurement_details
;
  1 omega   25.00  103.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       36.0421   57.0000  -60.0000 78

  2 omega  106.00  155.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000   61.0000 -150.0000 49

  3 omega  113.00  150.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000   30.0000  -30.0000 37

  4 omega   92.00  162.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000   45.0000 -180.0000 70

  5 omega   70.00  104.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -94.0000 -180.0000 34

  6 omega   43.00   70.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -30.0000 -180.0000 27

  7 omega    2.00   70.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       36.0421  -99.0000 -150.0000 68

  8 omega    2.00   53.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       36.0421  -99.0000    0.0000 51

  9 omega   38.00   63.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       36.0421  -77.0000    0.0000 25

 10 omega    9.00   52.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       36.0421  -57.0000   60.0000 43

 11 omega    4.00   60.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       36.0421  -99.0000  120.0000 56

 12 omega   38.00   80.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -30.0000   60.0000 42

 13 omega   45.00   85.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -61.0000  120.0000 40

 14 omega  100.00  126.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -61.0000  120.0000 26

 15 omega   42.00  107.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -94.0000   90.0000 65

 16 omega   41.00   72.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000  -45.0000  150.0000 31

 17 omega  -27.00    4.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       36.0421  -57.0000   60.0000 31

 18 omega  -32.00   11.00   1.0000    1.0000
omega____ theta____ kappa____ phi______ frames
    -       36.0421  -38.0000  -60.0000 43

 19 omega  109.00  134.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000  178.0000  150.0000 25

 20 omega   78.00  104.00   1.0000    3.0700
omega____ theta____ kappa____ phi______ frames
    -      108.0000  178.0000  150.0000 26
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'New Gemini, Dual, Cu at zero, EosS2'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.0377714000
_diffrn_orient_matrix_UB_12      -0.1034783000
_diffrn_orient_matrix_UB_13      0.0176533000
_diffrn_orient_matrix_UB_21      -0.1246553000
_diffrn_orient_matrix_UB_22      0.0388493000
_diffrn_orient_matrix_UB_23      0.0265176000
_diffrn_orient_matrix_UB_31      -0.0688508000
_diffrn_orient_matrix_UB_32      -0.0137391000
_diffrn_orient_matrix_UB_33      -0.0585105000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0267
_diffrn_reflns_av_unetI/netI     0.0316
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.974
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       23
_diffrn_reflns_limit_l_min       -28
_diffrn_reflns_number            12960
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.974
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.502
_diffrn_reflns_theta_min         4.229
_diffrn_source                   'Enhance (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.804
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.71493
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.288
_exptl_crystal_description       block
_exptl_crystal_F_000             1368
_exptl_crystal_size_max          0.7
_exptl_crystal_size_mid          0.45
_exptl_crystal_size_min          0.35
_refine_diff_density_max         0.405
_refine_diff_density_min         -0.535
_refine_diff_density_rms         0.150
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.033
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     431
_refine_ls_number_reflns         6464
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.033
_refine_ls_R_factor_all          0.0875
_refine_ls_R_factor_gt           0.0782
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1380P)^2^+0.6843P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2011
_refine_ls_wR_factor_ref         0.2138
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5300
_reflns_number_total             6464
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c8cc04732d2.cif
_cod_data_source_block           lq-0410
_cod_depositor_comments          'Adding full bibliography for 7121949.cif.'
_cod_database_code               7121949
_shelx_shelxl_version_number     2014/7
_reflns_odcompleteness_completeness 99.87
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2.a Ternary CH refined with riding coordinates:
 C1(H1A)
2.b Secondary CH2 refined with riding coordinates:
 C8(H8A,H8B), C22(H22A,H22B), C31(H31A,H31B)
2.c Aromatic/amide H refined with riding coordinates:
 C5(H5), C3(H3), C11(H11), C14(H14), C13(H13), C28(H28), C24(H24), C26(H26),
 C27(H27), C25(H25)
2.d Idealised Me refined as rotating group:
 C33(H33A,H33B,H33C), C19(H19A,H19B,H19C), C20(H20A,H20B,H20C), C21(H21A,H21B,
 H21C), C29(H29A,H29B,H29C), C32(H32A,H32B,H32C)
2.e Idealised tetrahedral OH refined as rotating group:
 O1(H1)
;
_shelx_res_checksum              76382
_olex2_date_sample_data_collection 2018-04-18
_olex2_submission_special_instructions 'No special instructions were received'