Synthesis of Thioether Andrographolide Derivatives and Their Inhibitory Effect Against Cancer Cells
Cheng, Chunru; Liu, Yi; Liang, Ren-Ming; Ma, Qing-Ping; Xu, Kai; Liang, Xin-Yong; Huang, Wei; Sutton, Robert; Ding, Jie; ONeill, P M; Med. Chem. Commun.  (2017) –; doi:10.1039/C7MD00169J

data_7120055
_publ_section_title
;
 Synthesis of Thioether Andrographolide Derivatives and Their Inhibitory
 Effect Against Cancer Cells
;
_journal_name_full               'Med. Chem. Commun.'
_journal_paper_doi               10.1039/C7MD00169J
_journal_year                    2017
_chemical_absolute_configuration syn
_chemical_formula_moiety         'C24 H32 O4 S2'
_chemical_formula_sum            'C24 H32 O4 S2'
_chemical_formula_weight         448.61
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2016-08-17
_audit_creation_method
;
Olex2 1.2-beta
(compiled 2016.07.08 svn.r3312 for OlexSys, GUI svn.r5206)
;
_audit_update_record
;
2016-10-05 deposited with the CCDC.
2017-04-26 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   9.859(3)
_cell_length_b                   13.570(5)
_cell_length_c                   17.593(6)
_cell_measurement_reflns_used    4185
_cell_measurement_temperature    296
_cell_measurement_theta_max      20.717
_cell_measurement_theta_min      2.316
_cell_volume                     2353.7(14)
_computing_cell_refinement       'SAINT v8.34A (Bruker, 2013)'
_computing_data_reduction        'SAINT v8.34A (Bruker, 2013)'
_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_temperature      296.15
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0397
_diffrn_reflns_av_unetI/netI     0.0466
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -22
_diffrn_reflns_number            16219
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.992
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.597
_diffrn_reflns_theta_min         1.895
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.253
_exptl_absorpt_correction_T_max  0.7456
_exptl_absorpt_correction_T_min  0.6601
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2014/5 (Bruker,2014/5) was used for absorption correction.
wR2(int) was 0.1178 before and 0.0623 after correction.
The Ratio of minimum to maximum transmission is 0.8853.
The \l/2 correction factor is 0.00150.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.266
_exptl_crystal_description       block
_exptl_crystal_F_000             960
_exptl_crystal_size_max          0.3
_exptl_crystal_size_mid          0.2
_exptl_crystal_size_min          0.15
_refine_diff_density_max         0.214
_refine_diff_density_min         -0.203
_refine_diff_density_rms         0.044
_refine_ls_abs_structure_details
;
 Flack x determined using 1069 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.02(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.009
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     293
_refine_ls_number_reflns         5421
_refine_ls_number_restraints     34
_refine_ls_restrained_S_all      1.030
_refine_ls_R_factor_all          0.1011
_refine_ls_R_factor_gt           0.0575
_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^)+(0.1098P)^2^+0.1042P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1611
_refine_ls_wR_factor_ref         0.1915
_reflns_Friedel_coverage         0.766
_reflns_Friedel_fraction_full    0.998
_reflns_Friedel_fraction_max     0.987
_reflns_number_gt                3254
_reflns_number_total             5421
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c7md00169j2.cif
_cod_data_source_block           mo_2016406_0m
_cod_database_code               7120055
_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. Restrained distances
 S2'-C21 = S2'-C24
 1.74 with sigma of 0.02
 C22-C21 = C23-C24
 1.3 with sigma of 0.02
 C22-C23
 1.54 with sigma of 0.02
 S2-C21 = S2-C23
 1.74 with sigma of 0.02
 C23-C24 = C21-C22'
 1.3 with sigma of 0.02
 C24-C22'
 1.58 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
Uanis(S2') \\sim Ueq, Uanis(C22') \\sim Ueq: with sigma of 0.1 and sigma for
terminal atoms of 0.2
Uanis(S2) \\sim Ueq, Uanis(C22') \\sim Ueq: with sigma of 0.1 and sigma for
terminal atoms of 0.2
Uanis(C24) \\sim Ueq, Uanis(C22') \\sim Ueq: with sigma of 0.005 and sigma for
terminal atoms of 0.01
4. Others
 Fixed Sof: S2(0.5) S2'(0.5) H24(0.5) H24A(0.5) H23A(0.5) H23(0.5) C22'(0.5)
 H22'(0.5) C22(0.5) H22(0.5)
5.a Ternary CH refined with riding coordinates:
 C11(H11), C5(H5), C16(H16), C7(H7)
5.b Secondary CH2 refined with riding coordinates:
 C15(H15A,H15B), C9(H9A,H9B), C4(H4A,H4B), C13(H13A,H13B), C19(H19A,H19B),
 C3(H3A,H3B), C8(H8A,H8B)
5.c Aromatic/amide H refined with riding coordinates:
 C20(H20), C24(H24), C24(H24A), C23(H23A), C23(H23), C22'(H22'), C22(H22)
5.d X=CH2 refined with riding coordinates:
 C1(H1A,H1B)
5.e Idealised Me refined as rotating group:
 C12(H12A,H12B,H12C), C14(H14A,H14B,H14C)
5.f Idealised tetrahedral OH refined as rotating group:
 O1(H1), O2(H2)
;
_shelx_shelxl_version_number     2014/7
_olex2_submission_special_instructions 'No special instructions were received'