Aniline-containing derivatives of parthenolide: Synthesis and anti-chronic lymphocytic leukaemia activity
Quy, Alex S.; Li, Xingjian; Male, Louise; Stankovic, Tatjana; Agathanggelou, Angelo; Fossey, John S.; Tetrahedron 76 (2020) 131631–; doi:10.1016/j.tet.2020.131631

data_1566134
_publ_section_title
;
 Aniline-containing derivatives of parthenolide: Synthesis and
 anti-chronic lymphocytic leukaemia activity
;
_journal_issue                   48
_journal_name_full               Tetrahedron
_journal_page_first              131631
_journal_paper_doi               10.1016/j.tet.2020.131631
_journal_volume                  76
_journal_year                    2020
_chemical_absolute_configuration syn
_chemical_formula_moiety         'C22 H29 N O3'
_chemical_formula_sum            'C22 H29 N O3'
_chemical_formula_weight         355.46
_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
_atom_sites_solution_primary     dual
_cell_angle_alpha                90
_cell_angle_beta                 93.143(2)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   11.1281(3)
_cell_length_b                   7.1835(2)
_cell_length_c                   11.8050(3)
_cell_measurement_reflns_used    17102
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      74.0470
_cell_measurement_theta_min      5.6180
_cell_volume                     942.26(4)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_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_environment      N~2~
_diffrn_ambient_temperature      100.00(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.1768
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.996
_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      1.00  28.00   1.00    2.57    --   38.00  92.00 118.64   27
  2  \w      0.00  26.00   1.00    2.57    --   38.00  94.00-130.37   26
  3  \w      7.00  33.00   1.00    2.57    --   42.00  88.00 -53.46   26
  4  \w    -74.00  32.00   1.00    2.57    --  -42.31  77.00-180.00  106
  5  \w   -115.00 -20.00   1.00    2.57    --  -42.31 -38.00 -90.00   95
  6  \w   -121.00  -5.00   1.00    2.57    --  -42.31 -19.00  60.00  116
  7  \w    -79.00  36.00   1.00    2.57    --  -42.31  19.00  60.00  115
  8  \w   -115.00 -20.00   1.00    2.57    --  -42.31 -38.00  60.00   95
  9  \w     16.00 112.00   1.00    2.57    --   42.31  57.00-120.00   96
 10  \w     23.00  97.00   1.00    2.57    --   42.31-125.00  30.00   74
 11  \w     13.00  40.00   1.00    2.57    --   46.00  83.00-101.14   27
 12  \w     18.00  45.00   1.00    2.57    --   50.00  78.00  35.04   27
 13  \w     27.00 132.00   1.00    2.57    --   58.00  77.00 -46.46  105
 14  \w     31.00 135.00   1.00    2.57    --   62.00  74.00 162.86  104
 15  \w     31.00 136.00   1.00    2.57    --   62.00  77.00-173.86  105
 16  \w     31.00 136.00   1.00    2.57    --   62.00  77.00  92.83  105
 17  \w     31.00 136.00   1.00    2.57    --   62.00  77.00 126.32  105
 18  \w     35.00 139.00   1.00    2.57    --   66.00  75.00 -80.00  104
 19  \w     35.00 139.00   1.00    2.57    --   66.00  76.00  58.37  104
 20  \w     37.00 137.00   1.00    2.57    --   66.00  67.00 142.80  100
 21  \w     41.00 141.00   1.00    2.57    --   70.00  68.00  83.22  100
 22  \w     39.00 143.00   1.00    2.57    --   70.00  76.00-138.56  104
 23  \w     39.00 143.00   1.00    2.57    --   70.00  75.00 -29.10  104
 24  \w     43.00 148.00   1.00    2.57    --   74.00  77.00  -3.60  105
 25  \w     43.00 148.00   1.00    2.57    --   74.00  77.00-100.76  105
 26  \w     43.00 147.00   1.00    2.57    --   74.00  76.00-114.85  104
 27  \w     43.00 147.00   1.00    2.57    --   74.00  76.00  18.63  104
 28  \w     60.00 162.00   1.00   10.29    --   90.00  71.00 -54.25  102
 29  \w     63.00 167.00   1.00   10.29    --   94.00  76.00  -0.52  104
 30  \w     33.00 113.00   1.00   10.29    --  106.63-118.00  91.00   80
 31  \w     79.00 177.00   1.00   10.29    --  106.63  61.00 -30.00   98
 32  \w     78.00 177.00   1.00   10.29    --  106.63  65.00  49.86   99
 33  \w     75.00 178.00   1.00   10.29    --  106.63  77.00 -90.00  103
 34  \w     79.00 177.00   1.00   10.29    --  106.63  61.00-120.00   98
 35  \w     25.00 109.00   1.00   10.29    --  106.63 -94.00 -90.00   84
 36  \w     75.00 178.00   1.00   10.29    --  106.63  77.00 120.00  103
 37  \w     79.00 177.00   1.00   10.29    --  106.63  61.00 120.00   98
 38  \w     79.00 177.00   1.00   10.29    --  106.63  61.00  90.00   98
 39  \w     75.00 178.00   1.00   10.29    --  106.63  77.00 150.00  103
 40  \w     79.00 177.00   1.00   10.29    --  106.63  61.00-150.00   98
 41  \w     25.00 109.00   1.00   10.29    --  106.63 -94.00-150.00   84
 42  \w     25.00 109.00   1.00   10.29    --  106.63 -94.00 -30.00   84
 43  \w     75.00 178.00   1.00   10.29    --  106.63  77.00 -60.00  103
 44  \w     79.00 177.00   1.00   10.29    --  106.63  61.00  30.00   98
 45  \w     79.00 177.00   1.00   10.29    --  106.63  61.00 150.00   98
 46  \w     75.00 178.00   1.00   10.29    --  106.63  77.00  90.00  103
 47  \w     25.00 109.00   1.00   10.29    --  106.63 -94.00 120.00   84
 48  \w     75.00 178.00   1.00   10.29    --  106.63  77.00-120.00  103
 49  \w     79.00 177.00   1.00   10.29    --  106.63  61.00-180.00   98
 50  \w     75.00 178.00   1.00   10.29    --  106.63  77.00  60.00  103
 51  \w     23.00  97.00   1.00    2.57    --   42.31-125.00 -90.00   74
 52  \w     16.00 118.00   1.00    2.57    --   46.00  73.00  67.04  102
 53  \w     18.00  45.00   1.00    2.57    --   50.00  79.00 -64.25   27
 54  \w     18.00  45.00   1.00    2.57    --   50.00  80.00  -1.94   27
 55  \w     23.00 127.00   1.00    2.57    --   54.00  75.00 -12.54  104
 56  \w     27.00 132.00   1.00    2.57    --   58.00  77.00 175.50  105
 57  \w     35.00 140.00   1.00    2.57    --   66.00  77.00-116.60  105
 58  \w     35.00 139.00   1.00    2.57    --   66.00  76.00-136.90  104
 59  \w     35.00 139.00   1.00    2.57    --   66.00  75.00-157.87  104
 60  \w     39.00 144.00   1.00    2.57    --   70.00  77.00  33.35  105
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.1051359000
_diffrn_orient_matrix_UB_12      -0.0109053000
_diffrn_orient_matrix_UB_13      -0.0902902000
_diffrn_orient_matrix_UB_21      -0.0900856000
_diffrn_orient_matrix_UB_22      0.0307678000
_diffrn_orient_matrix_UB_23      0.0927664000
_diffrn_orient_matrix_UB_31      0.0075892000
_diffrn_orient_matrix_UB_32      0.2119257000
_diffrn_orient_matrix_UB_33      -0.0180758000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0431
_diffrn_reflns_av_unetI/netI     0.0198
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            33890
_diffrn_reflns_point_group_measured_fraction_full 0.975
_diffrn_reflns_point_group_measured_fraction_max 0.961
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.427
_diffrn_reflns_theta_min         3.750
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.654
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.710
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46 (Rigaku Oxford Diffraction, 2018)
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            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.253
_exptl_crystal_description       plate
_exptl_crystal_F_000             384
_exptl_crystal_size_max          0.184
_exptl_crystal_size_mid          0.129
_exptl_crystal_size_min          0.026
_refine_diff_density_max         0.163
_refine_diff_density_min         -0.145
_refine_diff_density_rms         0.031
_refine_ls_abs_structure_details
;
 Flack x determined using 1513 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.03(8)
_refine_ls_extinction_coef       .
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.003
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     242
_refine_ls_number_reflns         3695
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.003
_refine_ls_R_factor_all          0.0303
_refine_ls_R_factor_gt           0.0287
_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^)+(0.0393P)^2^+0.1963P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0708
_refine_ls_wR_factor_ref         0.0719
_reflns_Friedel_coverage         0.782
_reflns_Friedel_fraction_full    0.945
_reflns_Friedel_fraction_max     0.920
_reflns_number_gt                3558
_reflns_number_total             3695
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            3d.cif
_cod_data_source_block           3d
_cod_database_code               1566134
_chemical_oxdiff_formula         'C22 H29 O3 N1'
_reflns_odcompleteness_completeness 100.00
_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), C3(H3), C4(H4), C5(H5)
2.b Secondary CH2 refined with riding coordinates:
 C7(H7A,H7B), C8(H8A,H8B), C11(H11A,H11B), C12(H12A,H12B), C15(H15A,H15B)
2.c Aromatic/amide H refined with riding coordinates:
 C9(H9), C17(H17), C18(H18), C20(H20), C21(H21)
2.d Idealised Me refined as rotating group:
 C13(H13A,H13B,H13C), C14(H14A,H14B,H14C), C22(H22A,H22B,H22C)
;
_shelx_res_checksum              28522
_shelx_hkl_checksum              12874
_olex2_date_sample_data_collection 2019-03-29
_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 1.417
_oxdiff_exptl_absorpt_empirical_full_min 0.741