Chemical modification of ovatodiolide revealed a promising amino-prodrug with improved pharmacokinetic profile.
Xiang, Junhong; Zhang, Xuemei; Wang, Dehong; Li, Jiaxin; Li, Qiuying; Wang, Qin; Ding, Yahui; Chen, Tianyang; Sun, Yuanjun; Bao, Shiqi; Chen, Jing; Li, Dongmei; Wang, Liang; Chen, Yue; Chemical communications (Cambridge, England) 56 (2020) 11018–11021; doi:10.1039/c9cc07573a

data_7127103
_publ_section_title
;
 Chemical modification of ovatodiolide revealed a promising amino-prodrug
 with improved pharmacokinetic profile.
;
_journal_issue                   75
_journal_name_full
'Chemical communications (Cambridge, England)'
_journal_page_first              11018
_journal_page_last               11021
_journal_paper_doi               10.1039/c9cc07573a
_journal_volume                  56
_journal_year                    2020
_chemical_formula_moiety         'C25 H36 N2 O4'
_chemical_formula_sum            'C25 H36 N2 O4'
_chemical_formula_weight         428.56
_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
_atom_sites_solution_primary     dual
_audit_creation_date             2018-10-10
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2018-12-21 deposited with the CCDC.	2020-08-17 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 92.6127(4)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   13.93601(6)
_cell_length_b                   13.66097(8)
_cell_length_c                   14.35128(7)
_cell_measurement_reflns_used    40264
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      78.8050
_cell_measurement_theta_min      3.0900
_cell_volume                     2729.35(2)
_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_temperature      293(2)
_diffrn_detector                 'CCD plate'
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.989
_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      5.00  32.00   0.50    0.50    --    5.00 -15.00  80.00   54
  2  \w   -135.00 -93.00   0.50    0.50    --  -49.30 -15.00  80.00   84
  3  \w    -90.00 -58.00   0.50    0.50    --  -49.30 -15.00  80.00   64
  4  \w   -179.00-153.00   0.50    0.61    -- -110.00  15.00-108.00   52
  5  \w   -136.00 -42.00   0.50    0.61    -- -110.00 -15.00  80.00  188
  6  \w     29.00  94.00   0.50    0.50    --    5.00  57.00 -60.00  130
  7  \w     -3.00  24.00   0.50    0.50    --    5.00  57.00 -60.00   54
  8  \w    -78.00 -19.00   0.50    0.50    --  -49.30 -57.00   0.00  118
  9  \w    -52.00  34.00   0.50    0.50    --  -49.30  15.00-108.00  172
 10  \w   -139.00 -20.00   0.50    0.50    --  -49.30 -49.00 -59.02  238
 11  \w    -74.00  39.00   0.50    0.50    --  -49.30  38.00  60.00  226
 12  \w    -55.00 -29.00   0.50    0.50    --  -49.30  57.00   0.00   52
 13  \w   -102.00 -76.00   0.50    0.61    -- -110.00 -72.00 -60.00   52
 14  \w   -199.00 -52.00   0.50    0.61    -- -110.00 -19.00-120.00  294
 15  \w    -48.00 -22.00   0.50    0.61    -- -110.00  72.00   0.00   52
 16  \w   -157.00-132.00   0.50    0.61    -- -110.00 -72.00  71.62   50
 17  \w   -105.00 -79.00   0.50    0.61    -- -110.00 -72.00  71.62   52
 18  \w   -102.00 -77.00   0.50    0.61    -- -110.00 -71.00 -53.10   50
 19  \w    -69.00 -22.00   0.50    0.61    -- -110.00  57.00  30.00   94
 20  \w   -144.00 -21.00   0.50    0.61    -- -110.00  72.00  90.00  246
 21  \w   -186.00-137.00   0.50    0.61    -- -110.00 -47.00  62.12   98
 22  \w   -103.00 -77.00   0.50    0.61    -- -110.00 -72.00   0.00   52
 23  \w   -104.00 -78.00   0.50    0.61    -- -110.00 -69.00 -73.05   52
 24  \w   -106.00 -80.00   0.50    0.61    -- -110.00 -43.00 -85.66   52
 25  \w   -105.00 -80.00   0.50    0.61    -- -110.00 -47.00  62.12   50
 26  \w   -101.00 -76.00   0.50    0.61    -- -110.00 -72.00  60.00   50
 27  \w   -101.00 -76.00   0.50    0.61    -- -110.00 -72.00   9.49   50
 28  \w   -101.00 -76.00   0.50    0.61    -- -110.00 -72.00 -30.00   50
 29  \w   -113.00 -79.00   0.50    0.61    -- -110.00 -44.00 -42.48   68
 30  \w   -103.00 -77.00   0.50    0.61    -- -110.00 -68.00  39.21   52
 31  \w   -194.00-168.00   0.50    0.61    -- -110.00 -71.00 -53.10   52
 32  \w   -193.00-157.00   0.50    0.61    -- -110.00 -61.00 -13.78   72
 33  \w   -114.00 -75.00   0.50    0.61    -- -110.00  57.00  30.00   78
 34  \w   -105.00 -78.00   0.50    0.61    -- -110.00 -38.00 -60.00   54
 35  \w   -161.00 -79.00   0.50    0.61    -- -110.00 -38.00  30.00  164
 36  \w   -139.00 -22.00   0.50    0.61    -- -110.00  72.00  30.00  234
 37  \w   -101.00 -76.00   0.50    0.61    -- -110.00 -72.00  18.81   50
 38  \w   -199.00-171.00   0.50    0.61    -- -110.00 -38.00 -30.00   56
 39  \w   -104.00 -79.00   0.50    0.61    -- -110.00 -45.00 -59.12   50
 40  \w   -163.00-138.00   0.50    0.61    -- -110.00 -38.00 -30.00   50
 41  \w   -129.00 -77.00   0.50    0.61    -- -110.00 -38.00 -30.00  104
 42  \w   -195.00-169.00   0.50    0.61    -- -110.00 -70.00  50.52   52
 43  \w   -108.00 -76.00   0.50    0.61    -- -110.00 -37.00 -20.02   64
 44  \w   -101.00 -76.00   0.50    0.61    -- -110.00 -72.00 -90.00   50
 45  \w   -106.00 -80.00   0.50    0.61    -- -110.00 -41.00  17.12   52
 46  \w   -103.00 -77.00   0.50    0.61    -- -110.00 -69.00 -13.44   52
 47  \w   -104.00 -78.00   0.50    0.61    -- -110.00 -71.00 -34.35   52
 48  \w   -102.00 -77.00   0.50    0.61    -- -110.00 -70.00 -15.85   50
 49  \w   -109.00 -82.00   0.50    0.61    -- -110.00 -48.00  69.08   54
 50  \w   -101.00 -76.00   0.50    0.61    -- -110.00 -72.00 -40.61   50
 51  \w   -199.00 -79.00   0.50    0.61    -- -110.00 -44.00  51.18  240
 52  \w   -104.00 -79.00   0.50    0.61    -- -110.00 -43.00 -28.54   50
 53  \w   -105.00 -79.00   0.50    0.61    -- -110.00 -61.00  39.94   52
 54  \w   -103.00 -77.00   0.50    0.61    -- -110.00 -71.00 -77.65   52
 55  \w   -102.00 -24.00   0.50    0.61    -- -110.00  72.00  60.00  156
 56  \w   -105.00 -80.00   0.50    0.61    -- -110.00 -50.00   9.75   50
 57  \w   -105.00 -80.00   0.50    0.61    -- -110.00 -47.00  30.32   50
 58  \w   -105.00 -80.00   0.50    0.61    -- -110.00 -57.00  14.78   50
 59  \w   -113.00 -79.00   0.50    0.61    -- -110.00 -43.00 -89.84   68
 60  \w   -106.00 -80.00   0.50    0.61    -- -110.00 -49.00  41.81   52
 61  \w   -105.00 -79.00   0.50    0.61    -- -110.00 -61.00 -13.78   52
 62  \w   -104.00 -79.00   0.50    0.61    -- -110.00 -61.00  32.61   50
 63  \w   -104.00 -78.00   0.50    0.61    -- -110.00 -66.00 -75.28   52
 64  \w   -101.00 -76.00   0.50    0.61    -- -110.00 -72.00  30.00   50
 65  \w   -104.00 -78.00   0.50    0.61    -- -110.00 -69.00 -77.73   52
 66  \w   -103.00 -77.00   0.50    0.61    -- -110.00 -71.00  41.17   52
 67  \w   -101.00 -76.00   0.50    0.61    -- -110.00 -72.00  16.19   50
 68  \w   -173.00 -80.00   0.50    0.61    -- -110.00 -51.00 -68.19  186
 69  \w   -106.00 -80.00   0.50    0.61    -- -110.00 -57.00  60.00   52
 70  \w   -199.00-107.00   0.50    0.61    -- -110.00 -72.00  30.00  184
 71  \w   -105.00 -80.00   0.50    0.61    -- -110.00 -57.00 -54.80   50
 72  \w   -103.00 -77.00   0.50    0.61    -- -110.00 -69.00 -21.82   52
 73  \w   -105.00 -79.00   0.50    0.61    -- -110.00 -44.00-102.29   52
 74  \w   -105.00 -79.00   0.50    0.61    -- -110.00 -45.00 -62.54   52
 75  \w   -104.00 -78.00   0.50    0.61    -- -110.00 -64.00 -54.03   52
 76  \w   -104.00 -78.00   0.50    0.61    -- -110.00 -65.00 -68.34   52
 77  \w   -109.00 -78.00   0.50    0.61    -- -110.00 -65.00 -59.99   62
 78  \w   -104.00 -79.00   0.50    0.61    -- -110.00 -38.00   0.00   50
 79  \w   -104.00 -78.00   0.50    0.61    -- -110.00 -39.00 -31.91   52
 80  \w   -194.00-169.00   0.50    0.61    -- -110.00 -72.00  18.81   50
 81  \w   -104.00 -78.00   0.50    0.61    -- -110.00 -70.00  50.52   52
 82  \w   -105.00 -79.00   0.50    0.61    -- -110.00 -70.00 -86.15   52
 83  \w   -107.00 -81.00   0.50    0.61    -- -110.00 -70.00 -22.06   52
 84  \w   -198.00-145.00   0.50    0.61    -- -110.00 -72.00   0.00  106
 85  \w   -101.00 -75.00   0.50    0.61    -- -110.00 -36.00 -87.72   52
 86  \w   -108.00 -83.00   0.50    0.61    -- -110.00  72.00   0.00   50
;
_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      -0.0724778000
_diffrn_orient_matrix_UB_12      -0.0223376000
_diffrn_orient_matrix_UB_13      0.0750843000
_diffrn_orient_matrix_UB_21      -0.0829615000
_diffrn_orient_matrix_UB_22      0.0055069000
_diffrn_orient_matrix_UB_23      -0.0745401000
_diffrn_orient_matrix_UB_31      0.0105115000
_diffrn_orient_matrix_UB_32      -0.1103769000
_diffrn_orient_matrix_UB_33      -0.0189111000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0277
_diffrn_reflns_av_unetI/netI     0.0233
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.989
_diffrn_reflns_limit_h_max       17
_diffrn_reflns_limit_h_min       -17
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            65502
_diffrn_reflns_point_group_measured_fraction_full 0.967
_diffrn_reflns_point_group_measured_fraction_max 0.951
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         79.221
_diffrn_reflns_theta_min         3.082
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.702
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.11618
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46 (Rigaku Oxford Diffraction, 2018)
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    1.304
_exptl_crystal_description       block
_exptl_crystal_F_000             1160
_exptl_crystal_size_max          0.34
_exptl_crystal_size_mid          0.28
_exptl_crystal_size_min          0.26
_refine_diff_density_max         2.171
_refine_diff_density_min         -0.423
_refine_diff_density_rms         0.155
_refine_ls_abs_structure_details
;
 Flack x determined using 4723 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.04(7)
_refine_ls_extinction_coef       0.013(2)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2014/7 (Sheldrick 2014'
_refine_ls_goodness_of_fit_ref   1.607
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     566
_refine_ls_number_reflns         11249
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.607
_refine_ls_R_factor_all          0.1229
_refine_ls_R_factor_gt           0.1223
_refine_ls_shift/su_max          0.766
_refine_ls_shift/su_mean         0.029
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.2000P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.3198
_refine_ls_wR_factor_ref         0.3221
_reflns_Friedel_coverage         0.843
_reflns_Friedel_fraction_full    0.932
_reflns_Friedel_fraction_max     0.909
_reflns_number_gt                10908
_reflns_number_total             11249
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c9cc07573a2.cif
_cod_data_source_block           p20181010d
_cod_depositor_comments
;
Adding full bibliography for 7127102--7127103.cif.

2025-03-04
Z value changed to be consistent with given formula
                 miguel
;
_cod_original_formula_moiety         '0.8(C25 H36 N2 O4)'
_cod_original_formula_units_Z            5
_cod_database_code               7127103
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         C25H36N2O4
_reflns_odcompleteness_completeness 99.71
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     74.33
_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:
 C29(H29), C33(H33), C34(H34), C35(H35), C4(H4), C8(H8), C9(H9), C10(H10)
2.b Secondary CH2 refined with riding coordinates:
 C30(H30A,H30B), C37(H37A,H37B), C38(H38A,H38B), C41(H41A,H41B), C42(H42A,
 H42B), C45(H45A,H45B), C46(H46A,H46B), C47(H47A,H47B), C48(H48A,H48B),
 C49(H49A,H49B), C5(H5A,H5B), C12(H12A,H12B), C13(H13A,H13B), C16(H16A,H16B),
 C17(H17A,H17B), C20(H20A,H20B), C21(H21A,H21B), C22(H22A,H22B), C23(H23A,H23B),
  C24(H24A,H24B)
2.c Aromatic/amide H refined with riding coordinates:
 C28(H28), C32(H32), C40(H40), C3(H3A), C7(H7), C15(H15)
2.d Idealised Me refined as rotating group:
 C43(H43A,H43B,H43C), C44(H44A,H44B,H44C), C50(H50A,H50B,H50C), C18(H18A,H18B,
 H18C), C19(H19A,H19B,H19C), C25(H25A,H25B,H25C)
;
_shelx_res_checksum              36666
_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 6.868
_oxdiff_exptl_absorpt_empirical_full_min 0.714