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_4518258
_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 ad
_chemical_formula_moiety         'C26 H33 N O4 S'
_chemical_formula_sum            'C26 H33 N O4 S'
_chemical_formula_weight         455.59
_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             2020-06-04
_audit_creation_method
;
Olex2 1.3-ac4
(compiled 2019.10.09 svn.r3662 for Rigaku Oxford Diffraction, GUI svn.r5959)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   9.18072(12)
_cell_length_b                   9.24659(12)
_cell_length_c                   26.9361(3)
_cell_measurement_reflns_used    27018
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      76.2380
_cell_measurement_theta_min      3.2620
_cell_volume                     2286.62(5)
_computing_cell_refinement       'CrysAlisPro 1.171.40.63a (Rigaku OD, 2019)'
_computing_data_collection       'CrysAlisPro 1.171.40.63a (Rigaku OD, 2019)'
_computing_data_reduction        'CrysAlisPro 1.171.40.63a (Rigaku OD, 2019)'
_computing_molecular_graphics    'Olex2 1.3-ac4 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3-ac4 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT n/a (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.00(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_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    -25.00  68.00   0.50    0.12    --   46.75 -71.00  -4.00  186
  2  \w     26.00 119.00   0.50    0.12    --   46.75  71.00 126.00  186
  3  \w   -160.00 -67.00   0.50    0.49    --  -88.50 -71.00  -4.00  186
  4  \w    -87.00 -15.00   0.50    0.49    --  -88.50  71.00 126.00  144
  5  \w     86.00 178.00   0.50    0.49    --  106.69  71.00 126.00  184
  6  \w     34.00  87.00   0.50    0.49    --  106.69 -71.00  -4.00  106
  7  \w   -119.00 -25.00   0.50    0.12    --  -46.75 -71.00  -4.00  188
  8  \w   -119.00 -87.00   0.50    0.12    --  -46.75-125.00 150.00   64
  9  \w    -30.00  29.00   0.50    0.12    --  -46.75  19.00  90.00  118
 10  \w   -119.00 -87.00   0.50    0.12    --  -46.75-125.00 -60.00   64
 11  \w    -68.00  26.00   0.50    0.12    --  -46.75  71.00 126.00  188
 12  \w    -29.00  30.00   0.50    0.12    --   46.75 -19.00-120.00  118
 13  \w     83.00 119.00   0.50    0.12    --   46.75  57.00-150.00   72
 14  \w     83.00 119.00   0.50    0.12    --   46.75  57.00 120.00   72
 15  \w   -160.00-101.00   0.50    0.49    --  -88.50 -77.00  90.00  118
 16  \w   -160.00 -91.00   0.50    0.49    --  -88.50 -61.00 -30.00  138
 17  \w    -51.00 -16.00   0.50    0.49    --  -88.50  45.00 -30.00   70
 18  \w   -160.00-101.00   0.50    0.49    --  -88.50 -77.00  60.00  118
 19  \w    -51.00 -16.00   0.50    0.49    --  -88.50  45.00 -60.00   70
 20  \w   -160.00-101.00   0.50    0.49    --  -88.50 -77.00 -60.00  118
 21  \w     34.00 111.00   0.50    0.49    --  106.69-125.00 150.00  154
 22  \w     34.00  71.00   0.50    0.49    --  106.69 -61.00   0.00   74
 23  \w     34.00 105.00   0.50    0.49    --  106.69 -94.00-120.00  142
 24  \w     90.00 178.00   0.50    0.49    --  106.69  54.00  67.09  176
 25  \w     89.00 178.00   0.50    0.49    --  106.69  15.00-150.00  178
 26  \w     34.00 105.00   0.50    0.49    --  106.69 -94.00 -60.00  142
 27  \w     91.00 178.00   0.50    0.49    --  106.69  30.00 -90.00  174
 28  \w     34.00 111.00   0.50    0.49    --  106.69-125.00-120.00  154
 29  \w     34.00 107.00   0.50    0.49    --  106.69-102.00-166.37  146
 30  \w     34.00 101.00   0.50    0.49    --  106.69 -77.00 -60.00  134
 31  \w     34.00 111.00   0.50    0.49    --  106.69-125.00-150.00  154
 32  \w     34.00 101.00   0.50    0.49    --  106.69 -77.00-150.00  134
 33  \w     34.00 111.00   0.50    0.49    --  106.69-125.00  90.00  154
 34  \w     34.00 101.00   0.50    0.49    --  106.69 -77.00-120.00  134
 35  \w     95.00 178.00   0.50    0.49    --  106.69 125.00 150.00  166
 36  \w     34.00  71.00   0.50    0.49    --  106.69 -61.00  60.00   74
 37  \w     34.00 107.00   0.50    0.49    --  106.69-106.00  83.09  146
 38  \w   -119.00 -31.00   0.50    0.12    --  -46.75 -55.00  48.92  176
 39  \w     31.00 109.00   0.50    0.12    --   46.75  55.00 -50.90  156
 40  \w     32.00 119.00   0.50    0.12    --   46.75  52.00-127.71  174
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0827327000
_diffrn_orient_matrix_UB_12      0.1305006000
_diffrn_orient_matrix_UB_13      -0.0217690000
_diffrn_orient_matrix_UB_21      -0.1185805000
_diffrn_orient_matrix_UB_22      0.0178891000
_diffrn_orient_matrix_UB_23      -0.0399864000
_diffrn_orient_matrix_UB_31      -0.0851749000
_diffrn_orient_matrix_UB_32      0.1020082000
_diffrn_orient_matrix_UB_33      0.0346160000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0628
_diffrn_reflns_av_unetI/netI     0.0246
_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       33
_diffrn_reflns_limit_l_min       -32
_diffrn_reflns_number            43299
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 1.000
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.485
_diffrn_reflns_theta_min         3.281
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.525
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.573
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.63a (Rigaku Oxford Diffraction, 2019)
Numerical absorption correction based on gaussian integration over
			a multifaceted crystal model
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    1.323
_exptl_crystal_description       plate
_exptl_crystal_F_000             976
_exptl_crystal_size_max          0.161
_exptl_crystal_size_mid          0.129
_exptl_crystal_size_min          0.034
_refine_diff_density_max         0.191
_refine_diff_density_min         -0.321
_refine_diff_density_rms         0.039
_refine_ls_abs_structure_details
;
 Flack x determined using 1825 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.050(14)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.026
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     292
_refine_ls_number_reflns         4531
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.026
_refine_ls_R_factor_all          0.0346
_refine_ls_R_factor_gt           0.0338
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0410P)^2^+1.0078P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0839
_refine_ls_wR_factor_ref         0.0844
_reflns_Friedel_coverage         0.741
_reflns_Friedel_fraction_full    0.999
_reflns_Friedel_fraction_max     0.999
_reflns_number_gt                4412
_reflns_number_total             4531
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ml0c00534_si_002.cif
_cod_data_source_block           hpd114a
_cod_database_code               4518258
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         S1N1C20O5H20
_chemical_oxdiff_usercomment     NAC-01-192
_shelx_estimated_absorpt_t_max   0.950
_shelx_estimated_absorpt_t_min   0.791
_reflns_odcompleteness_completeness 99.96
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_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
2.a Ternary CH refined with riding coordinates:
 C2(H2), C16(H16), C7(H7), C13(H13), C17(H17), C11(H11), C10(H10), C1(H1)
2.b Secondary CH2 refined with riding coordinates:
 C6(H6A,H6B), C9(H9A,H9B), C12(H12A,H12B), C14(H14A,H14B), C15(H15A,H15B),
 C5(H5A,H5B)
2.c Aromatic/amide H refined with riding coordinates:
 C25(H25), C21(H21), C22(H22), C24(H24)
2.d Idealised Me refined as rotating group:
 C26(H26A,H26B,H26C), C18(H18A,H18B,H18C), C19(H19A,H19B,H19C)
;
_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 1.444
_oxdiff_exptl_absorpt_empirical_full_min 0.798