Synthesis, and QSAR analysis of anti-oncological active spiro-alkaloids.
Girgis, Adel S.; Panda, Siva S.; Farag, I. S. Ahmed; El-Shabiny, A M; Moustafa, A. M.; Ismail, Nasser S. M.; Pillai, Girinath G.; Panda, Chandramukhi S.; Hall, C. Dennis; Katritzky, Alan R.; Organic & biomolecular chemistry 13 (2015) 1741–1753; doi:10.1039/c4ob02149e

data_7154243
_publ_section_title
;
 Synthesis, and QSAR analysis of anti-oncological active spiro-alkaloids.
;
_journal_issue                   6
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              1741
_journal_page_last               1753
_journal_paper_doi               10.1039/c4ob02149e
_journal_volume                  13
_journal_year                    2015
_chemical_absolute_configuration rm
_chemical_formula_iupac          'C32 H32 Cl1 N3 O2'
_chemical_formula_moiety         'C32 H32 Cl1 N3 O2'
_chemical_formula_sum            'C32 H32 Cl N3 O2'
_chemical_formula_weight         526.08
_chemical_melting_point          514(1)
_chemical_name_systematic
5-Chloro-1',1''-dimethyl-4'-(4-methylphenyl)-5''-[(4-methylphenyl)methylidene]-dispiro[3H-indole-3,2'-pyrrolidine-3',3''-piperidine]-2(1H),4''-dione
_space_group_IT_number           14
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_Hall  '-P 2yn'
_symmetry_space_group_name_H-M   'P 1 21/n 1'
_atom_sites_solution_hydrogens   difmap
_atom_sites_solution_primary     direct
_audit_update_record
;
2014-09-29 deposited with the CCDC.
2014-12-09 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 96.3419(17)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   11.6216(6)
_cell_length_b                   20.8276(9)
_cell_length_c                   11.8949(7)
_cell_measurement_reflns_used    4788
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      30
_cell_measurement_theta_min      3
_cell_volume                     2861.5(3)
_computing_cell_refinement       'DENZO/SCALEPACK (Otwinowski & Minor, 1997)'
_computing_data_collection       'COLLECT (Nonius, 2001).'
_computing_data_reduction        'DENZO/SCALEPACK (Otwinowski & Minor, 1997)'
_computing_molecular_graphics    'CAMERON (Watkin et al., 1996)'
_computing_publication_material  'CRYSTALS (Betteridge et al., 2003)'
_computing_structure_refinement  'CRYSTALS (Betteridge et al., 2003)'
_computing_structure_solution    'SIR92 (Altomare et al., 1994)'
_diffrn_ambient_temperature      298(2)
_diffrn_measured_fraction_theta_full 0.992
_diffrn_measured_fraction_theta_max 0.843
_diffrn_measurement_device       '95mm CCD camera on \k-goniostat'
_diffrn_measurement_device_type  'Nonius 590 KappaCCD'
_diffrn_measurement_method       '\f & \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           'Mo K\a'
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.151
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       25
_diffrn_reflns_limit_k_min       -24
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            9983
_diffrn_reflns_theta_full        25.087
_diffrn_reflns_theta_max         28.188
_diffrn_reflns_theta_min         3.039
_diffrn_standards_decay_%        0
_diffrn_standards_interval_count 0
_diffrn_standards_interval_time  0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.166
_exptl_absorpt_correction_T_max  1.00
_exptl_absorpt_correction_T_min  1.00
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'DENZO/SCALEPACK (Otwinowski & Minor, 1997)'
_exptl_crystal_colour            Colorless
_exptl_crystal_density_diffrn    1.221
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       Needle
_exptl_crystal_F_000             1112
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: n-butanol'
_exptl_crystal_size_max          0.16
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.08
_refine_diff_density_max         0.27
_refine_diff_density_min         -0.33
_refine_ls_extinction_method     None
_refine_ls_goodness_of_fit_ref   1.0301
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     236
_refine_ls_number_reflns         1569
_refine_ls_number_restraints     147
_refine_ls_R_factor_all          0.3533
_refine_ls_R_factor_gt           0.0685
_refine_ls_shift/su_max          0.0062096
_refine_ls_shift/su_mean         0.0004345
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
;
 Method= Modified Sheldrick 
 w=1/[\s^2^(F^2^) + ( 0.10P)^2^ + 0.00P] 
 ,where P=(max(Fo^2^,0) + 2Fc^2^)/3 
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_all         0.2459
_refine_ls_wR_factor_gt          0.1331
_refine_ls_wR_factor_ref         0.1331
_reflns_limit_h_max              14
_reflns_limit_h_min              -14
_reflns_limit_k_max              25
_reflns_limit_k_min              0
_reflns_limit_l_max              15
_reflns_limit_l_min              0
_reflns_number_gt                1569
_reflns_number_total             4939
_reflns_threshold_expression     I>2.0\s(I)
_oxford_refine_ls_scale          0.1762(3)
_iucr_refine_instructions_details_constraints
;
BLOCK 
CONT SCALE 
CONT CL   (    1 ,X'S,U'S)  UNTIL C    (   32 ) 
CONT H    (  103 ,X'S)  UNTIL H    (   91 ) 
CONT H    (  151 ,X'S)  UNTIL H    (  131 ) 
RIDE N   (   2,X'S) H   (  21,X'S) 
END                                                                             
;
_iucr_refine_instructions_details_restraints
;
NO 
REM   HREST   START (DO NOT REMOVE THIS LINE) 
REM NO H   NO #H U MULT DIST 
REM C-H 
REM >4           1.5    .96 DISORDER 
REM 1      1     1.2    .93 C C-H (ACETYLENE) 
REM 1      2     1.2    .93 C-C(H)-C 
REM 1      3     1.2    .98 (C)3-C-H 
REM 2      1     1.2    .93 C=C-H(2) 
REM 2      2     1.2    .97 (C)2-C-(H)2 
REM 3      1     1.5    .96 C-C-(H)3 
REM N-H 
REM >4           1.5    .89 DISORDER 
REM 1      1     1.2    .86 N-N/H 
REM 1      2     1.2    .86 (C)2-N-H 
REM 1      3     1.2    .89 (C)3-N-H 
REM 2      1     1.2    .86 C-N-(H)2 
REM 2      2     1.2    .89 (C)2-N-(H)2 
REM 3      1     1.2    .89 C-H-(H)3 
REM O-H 
REM 1      1     1.5    .82 O-H 
REM 
REM DIST      ESD = 0.02 
REM VIB       ESD = 0.002 
REM ANGLE     ESD = 2.0 
REM            H1-N-R2 
DIST 0.86, 0.02 = 
CONT N ( 2) TO H(21) 
REST 0.084, 0.002 = H(21,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(21) TO N ( 2) TO C(17) 
CONT H(21) TO N ( 2) TO C(18) 
REM            1 H ON SP 3 
DIST 0.98, 0.02 = 
CONT C ( 1) TO H(11) 
REST 0.090, 0.002 = H(11,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(11) TO C ( 1) TO C(2) 
CONT H(11) TO C ( 1) TO C(9) 
CONT H(11) TO C ( 1) TO C(19) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 3) TO H(31) 
REST 0.137, 0.002 = H(31,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(31) TO C ( 3) TO C(2) 
CONT H(31) TO C ( 3) TO C(4) 
PLANAR C ( 3) C(2) C(4) H(31) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 4) TO H(41) 
REST 0.148, 0.002 = H(41,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(41) TO C ( 4) TO C(3) 
CONT H(41) TO C ( 4) TO C(5) 
PLANAR C ( 4) C(3) C(5) H(41) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 6) TO H(61) 
REST 0.138, 0.002 = H(61,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(61) TO C ( 6) TO C(5) 
CONT H(61) TO C ( 6) TO C(7) 
PLANAR C ( 6) C(5) C(7) H(61) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 7) TO H(71) 
REST 0.116, 0.002 = H(71,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(71) TO C ( 7) TO C(6) 
CONT H(71) TO C ( 7) TO C(2) 
PLANAR C ( 7) C(6) C(2) H(71) 
REM            3 H ON SP 3 
DIST 0.96, 0.02 = 
CONT C ( 8) TO H(83) 
CONT C ( 8) TO H(81) 
CONT C ( 8) TO H(82) 
REST 0.226, 0.002 = H(83,U[ISO]) 
REST 0.226, 0.002 = H(81,U[ISO]) 
REST 0.226, 0.002 = H(82,U[ISO]) 
ANGLE 109.54, 2.0 = 
CONT C(5) TO C ( 8) TO H(83) 
CONT C(5) TO C ( 8) TO H(81) 
CONT C(5) TO C ( 8) TO H(82) 
ANGLE 0.0, 2.0 = MEAN H(83) TO C ( 8) TO H(81) 
CONT H(83) TO C ( 8) TO H(82) 
CONT H(81) TO C ( 8) TO H(82) 
REM            2 H ON SP 3 
DIST 0.97, 0.02 = 
CONT C ( 9) TO H(92) 
CONT C ( 9) TO H(91) 
REST 0.111, 0.002 = H(92,U[ISO]) 
REST 0.111, 0.002 = H(91,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(92) TO C ( 9) TO C(1) 
CONT H(92) TO C ( 9) TO N(3) 
CONT H(91) TO C ( 9) TO C(1) 
CONT H(91) TO C ( 9) TO N(3) 
ANGLE 109.54, 2.0 = 
CONT H(92) TO C ( 9) TO H(91) 
REM            3 H ON SP 3 
DIST 0.96, 0.02 = 
CONT C ( 10) TO H(103) 
CONT C ( 10) TO H(101) 
CONT C ( 10) TO H(102) 
REST 0.177, 0.002 = H(103,U[ISO]) 
REST 0.177, 0.002 = H(101,U[ISO]) 
REST 0.177, 0.002 = H(102,U[ISO]) 
ANGLE 109.54, 2.0 = 
CONT N(3) TO C ( 10) TO H(103) 
CONT N(3) TO C ( 10) TO H(101) 
CONT N(3) TO C ( 10) TO H(102) 
ANGLE 0.0, 2.0 = MEAN H(103) TO C ( 10) TO H(101) 
CONT H(103) TO C ( 10) TO H(102) 
CONT H(101) TO C ( 10) TO H(102) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 13) TO H(131) 
REST 0.106, 0.002 = H(131,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(131) TO C ( 13) TO C(12) 
CONT H(131) TO C ( 13) TO C(14) 
PLANAR C ( 13) C(12) C(14) H(131) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 15) TO H(151) 
REST 0.114, 0.002 = H(151,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(151) TO C ( 15) TO C(14) 
CONT H(151) TO C ( 15) TO C(16) 
PLANAR C ( 15) C(14) C(16) H(151) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 16) TO H(161) 
REST 0.096, 0.002 = H(161,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(161) TO C ( 16) TO C(15) 
CONT H(161) TO C ( 16) TO C(17) 
PLANAR C ( 16) C(15) C(17) H(161) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 22) TO H(221) 
REST 0.086, 0.002 = H(221,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(221) TO C ( 22) TO C(21) 
CONT H(221) TO C ( 22) TO C(23) 
PLANAR C ( 22) C(21) C(23) H(221) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 24) TO H(241) 
REST 0.103, 0.002 = H(241,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(241) TO C ( 24) TO C(23) 
CONT H(241) TO C ( 24) TO C(25) 
PLANAR C ( 24) C(23) C(25) H(241) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 25) TO H(251) 
REST 0.128, 0.002 = H(251,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(251) TO C ( 25) TO C(24) 
CONT H(251) TO C ( 25) TO C(26) 
PLANAR C ( 25) C(24) C(26) H(251) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 27) TO H(271) 
REST 0.121, 0.002 = H(271,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(271) TO C ( 27) TO C(26) 
CONT H(271) TO C ( 27) TO C(28) 
PLANAR C ( 27) C(26) C(28) H(271) 
REM            1 H ON SP 2 
DIST 0.93, 0.02 = 
CONT C ( 28) TO H(281) 
REST 0.101, 0.002 = H(281,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(281) TO C ( 28) TO C(23) 
CONT H(281) TO C ( 28) TO C(27) 
PLANAR C ( 28) C(23) C(27) H(281) 
REM            3 H ON SP 3 
DIST 0.96, 0.02 = 
CONT C ( 29) TO H(292) 
CONT C ( 29) TO H(293) 
CONT C ( 29) TO H(291) 
REST 0.250, 0.002 = H(292,U[ISO]) 
REST 0.250, 0.002 = H(293,U[ISO]) 
REST 0.250, 0.002 = H(291,U[ISO]) 
ANGLE 109.54, 2.0 = 
CONT C(26) TO C ( 29) TO H(292) 
CONT C(26) TO C ( 29) TO H(293) 
CONT C(26) TO C ( 29) TO H(291) 
ANGLE 0.0, 2.0 = MEAN H(292) TO C ( 29) TO H(293) 
CONT H(292) TO C ( 29) TO H(291) 
CONT H(293) TO C ( 29) TO H(291) 
REM            2 H ON SP 3 
DIST 0.97, 0.02 = 
CONT C ( 30) TO H(301) 
CONT C ( 30) TO H(302) 
REST 0.078, 0.002 = H(301,U[ISO]) 
REST 0.078, 0.002 = H(302,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(301) TO C ( 30) TO C(21) 
CONT H(301) TO C ( 30) TO N(1) 
CONT H(302) TO C ( 30) TO C(21) 
CONT H(302) TO C ( 30) TO N(1) 
ANGLE 109.54, 2.0 = 
CONT H(301) TO C ( 30) TO H(302) 
REM            2 H ON SP 3 
DIST 0.97, 0.02 = 
CONT C ( 31) TO H(312) 
CONT C ( 31) TO H(311) 
REST 0.087, 0.002 = H(312,U[ISO]) 
REST 0.087, 0.002 = H(311,U[ISO]) 
ANGLE 0.0, 2.0 = MEAN 
CONT H(312) TO C ( 31) TO C(19) 
CONT H(312) TO C ( 31) TO N(1) 
CONT H(311) TO C ( 31) TO C(19) 
CONT H(311) TO C ( 31) TO N(1) 
ANGLE 109.54, 2.0 = 
CONT H(312) TO C ( 31) TO H(311) 
REM            3 H ON SP 3 
DIST 0.96, 0.02 = 
CONT C ( 32) TO H(322) 
CONT C ( 32) TO H(323) 
CONT C ( 32) TO H(321) 
REST 0.125, 0.002 = H(322,U[ISO]) 
REST 0.125, 0.002 = H(323,U[ISO]) 
REST 0.125, 0.002 = H(321,U[ISO]) 
ANGLE 109.54, 2.0 = 
CONT N(1) TO C ( 32) TO H(322) 
CONT N(1) TO C ( 32) TO H(323) 
CONT N(1) TO C ( 32) TO H(321) 
ANGLE 0.0, 2.0 = MEAN H(322) TO C ( 32) TO H(323) 
CONT H(322) TO C ( 32) TO H(321) 
CONT H(323) TO C ( 32) TO H(321) 
REM   HREST   END (DO NOT REMOVE THIS LINE) 
END                                                                             
;
_cod_data_source_file            c4ob02149e2.cif
_cod_data_source_block           872_4a
_cod_depositor_comments          'Adding full bibliography for 7154243.cif.'
_cod_original_sg_symbol_H-M      'P 1 21/n 1 '
_cod_original_formula_sum        'C32 H32 Cl1 N3 O2'
_cod_database_code               7154243