Modular Total Synthesis and Cell-Based Anticancer Activity Evaluation of Ouabagenin and Other Cardiotonic Steroids with Varying Degrees of Oxygenation.
Khatri, Hem Raj; Bhattarai, Bijay; Kaplan, Will; Li, Zhongzheng; Curtis Long, Marcus John; Aye, Yimon; Nagorny, Pavel; Journal of the American Chemical Society 141 (2019) 4849–4860; doi:10.1021/jacs.8b12870

data_4129023
_publ_section_title
;
 Modular Total Synthesis and Cell-Based Anticancer Activity Evaluation of
 Ouabagenin and Other Cardiotonic Steroids with Varying Degrees of
 Oxygenation.
;
_journal_issue                   12
_journal_name_full               'Journal of the American Chemical Society'
_journal_page_first              4849
_journal_page_last               4860
_journal_paper_doi               10.1021/jacs.8b12870
_journal_volume                  141
_journal_year                    2019
_chemical_absolute_configuration syn
_chemical_formula_moiety         'C19 H26 O5'
_chemical_formula_sum            'C19 H26 O5'
_chemical_formula_weight         334.40
_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'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2017-01-11
_audit_creation_method
;
Olex2 1.2
(compiled 2017.01.04 svn.r3372 for OlexSys, GUI svn.r5289)
;
_audit_update_record
;
????
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.3267(2)
_cell_length_b                   8.6439(3)
_cell_length_c                   29.680(2)
_cell_measurement_reflns_used    11270
_cell_measurement_temperature    95
_cell_measurement_theta_max      66.5
_cell_measurement_theta_min      6.8
_cell_volume                     1623.12(13)
_computing_cell_refinement
;
CrystalClear-SM Expert 2.0 r15 (Rigaku, 2011)
;
_computing_data_collection
;
CrystalClear-SM Expert 2.0 r15 (Rigaku, 2011)
;
_computing_data_reduction
;
CrystalClear-SM Expert 2.0 r15 (Rigaku, 2011)
;
_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      95
_diffrn_detector                 'Image Plate'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            'Rigaku IP'
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_details
;
scan:
	Number of images: 72
	           Slice: 20.0000 - 200.0000
	     Image width: 2.5000
	        Exp time: 360.0000
	   Rotation axis: Omega
	           Omega: 0.0000
	             Chi: 54.0000
	             Phi: 0.0000
	             XTD: 127.4000
	          2theta: 0.0000
scan:
	Number of images: 72
	           Slice: 20.0000 - 200.0000
	     Image width: 2.5000
	        Exp time: 360.0000
	   Rotation axis: Omega
	           Omega: 0.0000
	             Chi: 54.0000
	             Phi: 90.0000
	             XTD: 127.4000
	          2theta: 0.0000
scan:
	Number of images: 72
	           Slice: 20.0000 - 200.0000
	     Image width: 2.5000
	        Exp time: 360.0000
	   Rotation axis: Omega
	           Omega: 0.0000
	             Chi: 54.0000
	             Phi: 180.0000
	             XTD: 127.4000
	          2theta: 0.0000
scan:
	Number of images: 72
	           Slice: 20.0000 - 200.0000
	     Image width: 2.5000
	        Exp time: 360.0000
	   Rotation axis: Omega
	           Omega: 0.0000
	             Chi: 0.0000
	             Phi: 0.0000
	             XTD: 127.4000
	          2theta: 0.0000
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Rigaku R-AXIS SPIDER IP'
_diffrn_measurement_method       '\w scans'
_diffrn_measurement_specimen_support Fiber
_diffrn_orient_matrix_type       FS_PROCESS
_diffrn_orient_matrix_UB_11      -0.032922
_diffrn_orient_matrix_UB_12      -0.113137
_diffrn_orient_matrix_UB_13      -0.000443
_diffrn_orient_matrix_UB_21      -0.098647
_diffrn_orient_matrix_UB_22      0.014147
_diffrn_orient_matrix_UB_23      0.026009
_diffrn_orient_matrix_UB_31      -0.119030
_diffrn_orient_matrix_UB_32      0.019589
_diffrn_orient_matrix_UB_33      -0.021415
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0301
_diffrn_reflns_av_unetI/netI     0.0182
_diffrn_reflns_Laue_measured_fraction_full 0.996
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       35
_diffrn_reflns_limit_l_min       -35
_diffrn_reflns_number            2861
_diffrn_reflns_point_group_measured_fraction_full 0.994
_diffrn_reflns_point_group_measured_fraction_max 0.994
_diffrn_reflns_theta_full        66.547
_diffrn_reflns_theta_max         66.547
_diffrn_reflns_theta_min         6.801
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_current           40.0
_diffrn_source_power             2.0
_diffrn_source_target            Mo
_diffrn_source_voltage           50.0
_exptl_absorpt_coefficient_mu    0.800
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.918
_exptl_absorpt_correction_type   empirical
_exptl_absorpt_process_details   'empirical process implemented in FS_Process'
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.368
_exptl_crystal_description       block
_exptl_crystal_F_000             720
_exptl_crystal_preparation       '1 mg sample was dissolved in 100 ul methanol'
_exptl_crystal_recrystallization_method
'Slow evapration from methanolic solution at room temperature for a week'
_exptl_crystal_size_max          0.14
_exptl_crystal_size_mid          0.14
_exptl_crystal_size_min          0.12
_refine_diff_density_max         0.352
_refine_diff_density_min         -0.226
_refine_diff_density_rms         0.078
_refine_ls_abs_structure_details
;
 Flack x determined using 1088 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.03(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.145
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     222
_refine_ls_number_reflns         2861
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.145
_refine_ls_R_factor_all          0.0435
_refine_ls_R_factor_gt           0.0415
_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^)+(0.0564P)^2^+0.9929P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1017
_refine_ls_wR_factor_ref         0.1111
_reflns_Friedel_coverage         0.685
_reflns_Friedel_fraction_full    0.991
_reflns_Friedel_fraction_max     0.991
_reflns_number_gt                2780
_reflns_number_total             2861
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ja8b12870_si_005.cif
_cod_data_source_block           merge-nofrpair-new
_cod_original_cell_volume        1623.10(14)
_cod_database_code               4129023
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_max   0.856
_shelx_estimated_absorpt_t_min   0.856
_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:
 C5(H5A), C6(H6), C9(H9), C13(H13)
2.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C3(H3A,H3B), C7(H7A,H7B), C10(H10A,H10B), C11(H11A,H11B),
 C18(H18A,H18B)
2.c Aromatic/amide H refined with riding coordinates:
 C14(H14), C15(H15), C17(H17)
2.d Idealised Me refined as rotating group:
 C19(H19A,H19B,H19C)
2.e Idealised tetrahedral OH refined as rotating group:
 O2(H2), O3(H3), O4(H4), O5(H5)
;
_olex2_exptl_crystal_mounting_method
'coated in mineral oil and mount in a cryoloop'
_olex2_submission_original_sample_id HK-I-214-b
_olex2_submission_special_instructions 'No special instructions were received'