Synthesis and Biological Evaluations of Electrophilic Steroids Inspired by the Taccalonolides
Clanton, Nicholas A.; Hastings, Shayne D.; Foultz, Griffin B.; Contreras, Julie A.; Yee, Samantha S.; Arman, Hadi D.; Risinger, April L.; Frantz, Doug E.; ACS Medicinal Chemistry Letters  (2020) –; doi:10.1021/acsmedchemlett.0c00534

data_4518259
_publ_section_title
;
 Synthesis and Biological Evaluations of Electrophilic Steroids Inspired
 by the Taccalonolides
;
_journal_name_full               'ACS Medicinal Chemistry Letters'
_journal_paper_doi               10.1021/acsmedchemlett.0c00534
_journal_year                    2020
_chemical_absolute_configuration unk
_chemical_formula_moiety         'C19 H26 O2'
_chemical_formula_sum            'C19 H26 O2'
_chemical_formula_weight         286.40
_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   geom
_audit_creation_date             2020-09-23
_audit_creation_method
;
Olex2 1.3
(compiled 2020.07.31 svn.rc2a77460 for OlexSys, GUI svn.r6145)
;
_cell_angle_alpha                90
_cell_angle_beta                 100.184(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   7.6756(2)
_cell_length_b                   20.7238(5)
_cell_length_c                   9.8982(3)
_cell_measurement_reflns_used    11421
_cell_measurement_temperature    98(2)
_cell_measurement_theta_max      29.0930
_cell_measurement_theta_min      2.8300
_cell_volume                     1549.68(7)
_computing_cell_refinement       'CrysAlisPro 1.171.39.28e (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.39.28e (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.39.28e (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2014/7 (Sheldrick, 2015)'
_diffrn_ambient_temperature      98(2)
_diffrn_detector                 'CCD plate'
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
--------------------------------------------------------------------------
  1  \w    -85.00  36.00   1.00   15.00    --    4.20 -67.00-161.00  121
  2  \w    -39.00  82.00   1.00   15.00    --   -7.60  67.00 -27.00  121
  3  \w    -32.00  82.00   1.00   15.00    --   -7.60  38.00  90.00  114
  4  \w    -32.00  82.00   1.00   15.00    --   -7.60  38.00 -90.00  114
  5  \w    -97.00 -44.00   1.00   15.00    --   -7.60 -72.00 150.00   53
  6  \w    -40.00  82.00   1.00   15.00    --   -7.60  72.00 150.00  122
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB AFC12 (RCD3): Kappa single'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0872573000
_diffrn_orient_matrix_UB_12      -0.0020619000
_diffrn_orient_matrix_UB_13      -0.0141564000
_diffrn_orient_matrix_UB_21      0.0181563000
_diffrn_orient_matrix_UB_22      -0.0260803000
_diffrn_orient_matrix_UB_23      0.0467610000
_diffrn_orient_matrix_UB_31      -0.0295228000
_diffrn_orient_matrix_UB_32      -0.0220710000
_diffrn_orient_matrix_UB_33      -0.0539713000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Mo K\a'
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0360
_diffrn_reflns_av_unetI/netI     0.0283
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       25
_diffrn_reflns_limit_k_min       -25
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            29503
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.999
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         25.996
_diffrn_reflns_theta_min         2.310
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.077
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.97922
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.28e (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.228
_exptl_crystal_description       block
_exptl_crystal_F_000             624
_exptl_crystal_size_max          0.36
_exptl_crystal_size_mid          0.33
_exptl_crystal_size_min          0.3
_refine_diff_density_max         0.498
_refine_diff_density_min         -0.219
_refine_diff_density_rms         0.040
_refine_ls_abs_structure_details
;
 Flack x determined using 2620 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.1(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.064
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     392
_refine_ls_number_reflns         6090
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.064
_refine_ls_R_factor_all          0.0464
_refine_ls_R_factor_gt           0.0457
_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^)+(0.0400P)^2^+0.8000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1024
_refine_ls_wR_factor_ref         0.1028
_reflns_Friedel_coverage         0.943
_reflns_Friedel_fraction_full    0.999
_reflns_Friedel_fraction_max     0.999
_reflns_number_gt                6003
_reflns_number_total             6090
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ml0c00534_si_003.cif
_cod_data_source_block           cd1831
_cod_database_code               4518259
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         O2C19H26
_chemical_oxdiff_usercomment     NAC-224-89
_shelx_estimated_absorpt_t_max   0.977
_shelx_estimated_absorpt_t_min   0.973
_reflns_odcompleteness_completeness 99.88
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.32
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, {H20A,H20B,H20} of C20, {H35A,H35B,H35} of C35, All C(H,H)
  groups
 At 1.5 times of:
  {H19A,H19B,H19C} of C19, {H37A,H37B,H37C} of C37, {H38A,H38B,H38C} of C38,
  {H18A,H18B,H18C} of C18
2. Others
 Fixed Sof: O3A(0.65) H36A(0.65) H36(0.35) H20A(0.35) H20B(0.35) H20(0.65)
 H35A(0.65) H35B(0.65) H35(0.35) O3B(0.35)
3.a Ternary CH refined with riding coordinates:
 C31(H31), C4(H4), C23(H23), C30(H30), C12(H12), C11(H11), C17(H17), C34(H34),
 C15(H15), C1(H1), C36(H36A), C36(H36), C20(H20), C35(H35)
3.b Secondary CH2 refined with riding coordinates:
 C25(H25A,H25B), C24(H24A,H24B), C5(H5A,H5B), C6(H6A,H6B), C2(H2A,H2B),
 C13(H13A,H13B), C21(H21A,H21B), C33(H33A,H33B), C32(H32A,H32B), C14(H14A,H14B),
  C16(H16A,H16B), C20(H20A,H20B), C35(H35A,H35B)
3.c Aromatic/amide H refined with riding coordinates:
 C28(H28), C29(H29), C9(H9), C10(H10)
3.d Idealised Me refined as rotating group:
 C37(H37A,H37B,H37C), C38(H38A,H38B,H38C), C19(H19A,H19B,H19C), C18(H18A,H18B,
 H18C)
;
_shelx_res_checksum              87985
_shelx_hkl_checksum              71137
_olex2_exptl_crystal_mounting_method 'nylon loop'
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.050
_oxdiff_exptl_absorpt_empirical_full_min 0.947