Discovery of a Potent α-Galactosidase Inhibitor by in Situ Analysis of a Library of Pyrrolizidine-(Thio)urea Hybrid Molecules Generated via Click Chemistry.
Elías-Rodríguez, Pilar; Pingitore, Valeria; Carmona, Ana T.; Moreno-Vargas, Antonio J; Ide, Daisuke; Miyawaki, Shota; Kato, Atsushi; Álvarez, Eleuterio; Robina, Inmaculada; The Journal of organic chemistry 83 (2018) 8863–8873; doi:10.1021/acs.joc.8b01073

data_4035300
_publ_section_title
;
 Discovery of a Potent \a-Galactosidase Inhibitor by in Situ Analysis of a
 Library of Pyrrolizidine-(Thio)urea Hybrid Molecules Generated via Click
 Chemistry.
;
_journal_issue                   16
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              8863
_journal_page_last               8873
_journal_paper_doi               10.1021/acs.joc.8b01073
_journal_volume                  83
_journal_year                    2018
_chemical_absolute_configuration rmad
_chemical_formula_moiety         'C19 H21 F6 N3 O2 S, C H2 Cl2'
_chemical_formula_sum            'C20 H23 Cl2 F6 N3 O2 S'
_chemical_formula_weight         554.37
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   mixed
_audit_creation_method           SHELXL-2016/6
_cell_angle_alpha                90
_cell_angle_beta                 99.023(2)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   9.9180(4)
_cell_length_b                   9.8167(4)
_cell_length_c                   12.7446(5)
_cell_measurement_reflns_used    9922
_cell_measurement_temperature    193(2)
_cell_measurement_theta_max      30.47
_cell_measurement_theta_min      2.63
_cell_volume                     1225.49(9)
_computing_cell_refinement       'Bruker SAINT'
_computing_data_collection       'Bruker APEX2'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-2016/6 (Sheldrick, 2016)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 2008)'
_diffrn_ambient_temperature      193(2)
_diffrn_detector_area_resol_mean 8.26
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_diffrn_measurement_device_type
;
 Bruker-Nonius X8kappa APEX II CCD area detector
;
_diffrn_measurement_method       'phi and omega scans with narrow frames'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0289
_diffrn_reflns_av_unetI/netI     0.0256
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            18120
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 1.000
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         25.244
_diffrn_reflns_theta_min         2.079
_exptl_absorpt_coefficient_mu    0.419
_exptl_absorpt_correction_T_max  0.7461
_exptl_absorpt_correction_T_min  0.5275
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
program SADABS, Bruker (2001).
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.502
_exptl_crystal_description       needle
_exptl_crystal_F_000             568
_exptl_crystal_size_max          0.500
_exptl_crystal_size_mid          0.400
_exptl_crystal_size_min          0.400
_refine_diff_density_max         0.763
_refine_diff_density_min         -0.684
_refine_diff_density_rms         0.077
_refine_ls_abs_structure_details
; 
 Flack x determined using 1886 quotients [(I+)-(I-)]/[(I+)+(I-)] 
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259). 
;
_refine_ls_abs_structure_Flack   0.04(2)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.047
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     342
_refine_ls_number_reflns         4446
_refine_ls_number_restraints     135
_refine_ls_restrained_S_all      1.080
_refine_ls_R_factor_all          0.0514
_refine_ls_R_factor_gt           0.0494
_refine_ls_shift/su_max          0.024
_refine_ls_shift/su_mean         0.001
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1030P)^2^+0.7980P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1448
_refine_ls_wR_factor_ref         0.1465
_reflns_Friedel_coverage         0.882
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     1.000
_reflns_number_gt                4250
_reflns_number_total             4446
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo8b01073_si_002.cif
_cod_data_source_block           8a
_cod_original_sg_symbol_H-M      'P 21'
_cod_database_code               4035300
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_min   0.818
_shelx_estimated_absorpt_t_max   0.850
_shelx_res_checksum              89190
_shelx_hkl_checksum              89654
_shelx_fab_checksum              65135