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_1566133
_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 ad
_chemical_formula_moiety         'C21 H27 N O4, C3 H6 O'
_chemical_formula_sum            'C24 H33 N O5'
_chemical_formula_weight         415.51
_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     direct
_cell_angle_alpha                90
_cell_angle_beta                 107.1578(16)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   11.34175(18)
_cell_length_b                   8.21411(13)
_cell_length_c                   12.44906(19)
_cell_measurement_reflns_used    18852
_cell_measurement_temperature    99.98(12)
_cell_measurement_theta_max      73.8870
_cell_measurement_theta_min      3.6710
_cell_volume                     1108.17(3)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_collection
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2008)'
_computing_structure_solution    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      99.98(12)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.3537
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.994
_diffrn_measurement_details
;
  1 omega    7.00   34.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       42.0000   87.0000   41.4590 27

  2 omega -113.00  -16.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -      -42.4357  -57.0000 -150.0000 97

  3 omega -121.00   -6.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -      -42.4357  -19.0000   90.0000 115

  4 omega -113.00  -16.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -      -42.4357  -57.0000  -60.0000 97

  5 omega -115.00  -20.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -      -42.4357  -38.0000    0.0000 95

  6 omega   23.00   97.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       42.4357 -125.0000    0.0000 74

  7 omega   14.00  113.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       42.4357   65.0000   61.9032 99

  8 omega   23.00   97.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       42.4357 -125.0000 -150.0000 74

  9 omega    1.00   82.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       42.4357  -99.0000   90.0000 81

 10 omega   14.00   46.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       46.0000   81.0000  140.9322 32

 11 omega   17.00   45.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       50.0000   82.0000  -77.6395 28

 12 omega   17.00   45.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       50.0000   82.0000 -151.7162 28

 13 omega   27.00  131.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       58.0000   75.0000  168.8449 104

 14 omega   31.00  136.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       62.0000   77.0000   62.9293 105

 15 omega   31.00  135.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       62.0000   76.0000    3.0156 104

 16 omega   32.00  134.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       62.0000   73.0000  -85.7784 102

 17 omega   35.00  140.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       66.0000   77.0000   90.8591 105

 18 omega   35.00  139.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       66.0000   74.0000  -37.8503 104

 19 omega   35.00  139.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       66.0000   76.0000  118.3799 104

 20 omega   39.00  143.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       70.0000   75.0000 -151.4715 104

 21 omega   45.00  141.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       70.0000   51.0000 -156.6275 96

 22 omega   43.00  148.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       74.0000   77.0000  123.7087 105

 23 omega   46.00  144.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       74.0000   63.0000    6.5051 98

 24 omega   44.00  146.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       74.0000   72.0000   19.3713 102

 25 omega   43.00  147.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       74.0000   76.0000  -83.0060 104

 26 omega   55.00  152.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -       82.0000   60.0000   71.3805 97

 27 omega   52.00  154.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -       82.0000   70.0000   93.3808 102

 28 omega   59.00  156.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -       86.0000   60.0000  -99.9646 97

 29 omega   58.00  156.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -       86.0000   61.0000  -12.4797 98

 30 omega   59.00  163.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -       90.0000   76.0000  -55.4984 104

 31 omega   68.00  170.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -       98.0000   72.0000  -81.3507 102

 32 omega   94.00  178.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257  125.0000 -150.0000 84

 33 omega   75.00  178.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   77.0000  150.0000 103

 34 omega   75.00  178.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   77.0000   60.0000 103

 35 omega   75.00  178.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   77.0000 -180.0000 103

 36 omega   25.00  109.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257  -94.0000  -30.0000 84

 37 omega   75.00  178.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   77.0000  -60.0000 103

 38 omega   25.00  109.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257  -94.0000  120.0000 84

 39 omega   79.00  177.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   61.0000  150.0000 98

 40 omega   35.00   99.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257  -45.0000  -30.0000 64

 41 omega   75.00  178.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   77.0000    0.0000 103

 42 omega   35.00  122.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257 -125.0000  -60.0000 87

 43 omega   75.00  178.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   77.0000  -30.0000 103

 44 omega   79.00  177.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   61.0000  123.6998 98

 45 omega   75.00  178.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   77.0000  120.0000 103

 46 omega   75.00  178.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   77.0000   90.0000 103

 47 omega   79.00  177.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   61.0000 -150.0000 98

 48 omega   75.00  178.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   77.0000   30.0000 103

 49 omega   25.00  109.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257  -94.0000 -180.0000 84

 50 omega   75.00  178.00   1.0000    5.5750
omega____ theta____ kappa____ phi______ frames
    -      106.6257   77.0000 -120.0000 103

 51 omega    7.00   33.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       42.0000   89.0000  -77.7349 26

 52 omega  -50.00   30.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -      -42.4357   38.0000 -180.0000 80

 53 omega -121.00   -6.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -      -42.4357  -19.0000  -60.0000 115

 54 omega   18.00   47.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       50.0000   79.0000   58.0839 29

 55 omega   27.00  131.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       58.0000   76.0000   46.7335 104

 56 omega   27.00  131.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       58.0000   75.0000 -150.4686 104

 57 omega   33.00  133.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       62.0000   66.0000  -89.9884 100

 58 omega   39.00  143.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       70.0000   75.0000  -60.9584 104

 59 omega   40.00  142.00   1.0000    1.3950
omega____ theta____ kappa____ phi______ frames
    -       70.0000   71.0000   71.6763 102
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.1021187000
_diffrn_orient_matrix_UB_12      -0.0311481000
_diffrn_orient_matrix_UB_13      0.0561709000
_diffrn_orient_matrix_UB_21      -0.0975466000
_diffrn_orient_matrix_UB_22      0.0015585000
_diffrn_orient_matrix_UB_23      -0.1162691000
_diffrn_orient_matrix_UB_31      0.0164012000
_diffrn_orient_matrix_UB_32      -0.1848841000
_diffrn_orient_matrix_UB_33      -0.0103850000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0373
_diffrn_reflns_av_unetI/netI     0.0165
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.994
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            39001
_diffrn_reflns_point_group_measured_fraction_full 0.982
_diffrn_reflns_point_group_measured_fraction_max 0.965
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.439
_diffrn_reflns_theta_min         3.716
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.699
_exptl_absorpt_correction_T_max  0.809
_exptl_absorpt_correction_T_min  0.508
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
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            grey
_exptl_crystal_colour_primary    grey
_exptl_crystal_density_diffrn    1.245
_exptl_crystal_description       rod
_exptl_crystal_F_000             448
_exptl_crystal_size_max          0.2589
_exptl_crystal_size_mid          0.1037
_exptl_crystal_size_min          0.0591
_refine_diff_density_max         0.199
_refine_diff_density_min         -0.256
_refine_diff_density_rms         0.035
_refine_ls_abs_structure_details
;
 Flack x determined using 1819 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.07(6)
_refine_ls_extinction_coef       .
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.043
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     283
_refine_ls_number_reflns         4374
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.043
_refine_ls_R_factor_all          0.0345
_refine_ls_R_factor_gt           0.0323
_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^)+(0.0490P)^2^+0.2580P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0837
_refine_ls_wR_factor_ref         0.0857
_reflns_Friedel_coverage         0.809
_reflns_Friedel_fraction_full    0.961
_reflns_Friedel_fraction_max     0.931
_reflns_number_gt                4185
_reflns_number_total             4374
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            3b.cif
_cod_data_source_block           3b
_cod_database_code               1566133
_chemical_oxdiff_formula         'C12 H27 N O4'
_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:
 C1(H1), C9(H9), C10(H10), C13(H13)
2.b Secondary CH2 refined with riding coordinates:
 C3(H3A,H3B), C4(H4A,H4B), C7(H7A,H7B), C8(H8A,H8B), C15(H15A,H15B)
2.c Aromatic/amide H refined with riding coordinates:
 C5(H5), C17(H17), C18(H18), C20(H20), C21(H21)
2.d Idealised Me refined as rotating group:
 C11(H11A,H11B,H11C), C12(H12A,H12B,H12C), C102(H10A,H10B,H10C), C103(H10D,
 H10E,H10F)
;
_shelx_res_checksum              28560
_shelx_hkl_checksum              38214
_olex2_submission_special_instructions 'No special instructions were received'