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_7127102
_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_absolute_configuration ad
_chemical_formula_moiety         'C25 H36 N2 O6, 2(H2 O)'
_chemical_formula_sum            'C25 H40 N2 O8'
_chemical_formula_weight         496.59
_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
_audit_creation_date             2018-09-27
_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                 113.2519(6)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   10.65993(6)
_cell_length_b                   11.44033(5)
_cell_length_c                   11.66689(6)
_cell_measurement_reflns_used    25290
_cell_measurement_temperature    294.15
_cell_measurement_theta_max      78.6510
_cell_measurement_theta_min      3.8710
_cell_volume                     1307.250(13)
_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      294.15
_diffrn_detector                 PILT
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.995
_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    -84.00  37.00   0.50    0.50    --    5.00 -66.00  -9.00  242
  2  \w   -139.00 -17.00   0.50    0.50    --  -49.30 -66.00  -9.00  244
  3  \w   -142.00 -21.00   0.50    0.50    -- -110.00  66.00 125.00  242
  4  \w   -199.00 -78.00   0.50    0.50    -- -110.00 -66.00  -9.00  242
  5  \w    -27.00  94.00   0.50    0.50    --    5.00  66.00 125.00  242
  6  \w    -25.00  94.00   0.50    0.50    --    5.00  57.00-180.00  238
  7  \w   -139.00 -19.00   0.50    0.50    --  -49.30 -48.00  42.15  240
  8  \w   -139.00 -17.00   0.50    0.50    --  -49.30 -41.00-140.73  244
  9  \w    -83.00  40.00   0.50    0.50    --  -49.30  71.00-173.57  246
 10  \w   -199.00 -79.00   0.50    0.50    -- -110.00 -62.00  56.71  240
 11  \w   -199.00 -78.00   0.50    0.50    -- -110.00 -42.00-178.95  242
 12  \w   -199.00 -80.00   0.50    0.50    -- -110.00 -57.00  78.80  238
 13  \w   -140.00 -21.00   0.50    0.50    -- -110.00  57.00-120.00  238
 14  \w   -199.00 -77.00   0.50    0.50    -- -110.00 -38.00-150.00  244
 15  \w   -199.00 -52.00   0.50    0.50    -- -110.00 -19.00 -90.00  294
 16  \w   -199.00 -76.00   0.50    0.50    -- -110.00 -72.00  13.81  246
 17  \w   -199.00 -79.00   0.50    0.50    -- -110.00 -44.00-104.60  240
 18  \w   -199.00 -78.00   0.50    0.50    -- -110.00 -64.00 119.57  242
 19  \w   -199.00 -76.00   0.50    0.50    -- -110.00 -72.00  52.85  246
 20  \w   -199.00 -78.00   0.50    0.50    -- -110.00 -64.00 -38.53  242
 21  \w   -199.00 -76.00   0.50    0.50    -- -110.00 -72.00 -90.00  246
 22  \w   -199.00 -79.00   0.50    0.50    -- -110.00 -45.00  51.74  240
 23  \w   -199.00 -52.00   0.50    0.50    -- -110.00 -19.00 -90.00  294
 24  \w   -140.00 -21.00   0.50    0.50    -- -110.00  57.00 150.00  238
 25  \w   -199.00 -80.00   0.50    0.50    -- -110.00 -57.00-150.00  238
 26  \w   -199.00 -80.00   0.50    0.50    -- -110.00 -48.00-115.50  238
 27  \w   -139.00 -18.00   0.50    0.50    --  -49.30 -45.00 122.53  242
 28  \w   -139.00 -15.00   0.50    0.50    --  -49.30 -72.00 -72.00  248
 29  \w    -80.00  40.00   0.50    0.50    --  -49.30  57.00  30.00  240
 30  \w    -83.00  40.00   0.50    0.50    --  -49.30  38.00   0.00  246
;
_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      0.0043408000
_diffrn_orient_matrix_UB_12      0.0537829000
_diffrn_orient_matrix_UB_13      -0.1194611000
_diffrn_orient_matrix_UB_21      0.1105794000
_diffrn_orient_matrix_UB_22      0.0867386000
_diffrn_orient_matrix_UB_23      0.0797345000
_diffrn_orient_matrix_UB_31      0.1117493000
_diffrn_orient_matrix_UB_32      -0.0878649000
_diffrn_orient_matrix_UB_33      0.0056265000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0238
_diffrn_reflns_av_unetI/netI     0.0117
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.995
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            31811
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.988
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         78.962
_diffrn_reflns_theta_min         4.124
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.773
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.64811
_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    1.262
_exptl_crystal_description       block
_exptl_crystal_F_000             536
_exptl_crystal_size_max          0.28
_exptl_crystal_size_mid          0.24
_exptl_crystal_size_min          0.22
_refine_diff_density_max         0.156
_refine_diff_density_min         -0.140
_refine_diff_density_rms         0.024
_refine_ls_abs_structure_details
;
 Flack x determined using 2534 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.03(3)
_refine_ls_extinction_coef       0.0089(8)
_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   1.045
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     326
_refine_ls_number_reflns         5591
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.045
_refine_ls_R_factor_all          0.0323
_refine_ls_R_factor_gt           0.0320
_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^)+(0.0532P)^2^+0.1064P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0908
_refine_ls_wR_factor_ref         0.0911
_reflns_Friedel_coverage         0.888
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.980
_reflns_number_gt                5505
_reflns_number_total             5591
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c9cc07573a2.cif
_cod_data_source_block           p20180927a
_cod_depositor_comments
'Adding full bibliography for 7127102--7127103.cif.'
_cod_original_cell_volume        1307.249(13)
_cod_database_code               7127102
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         C25H36N2O6
_reflns_odcompleteness_completeness 100.00
_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, All O(H,H) groups
2.a Free rotating group:
 O7(H7C,H7D), O8(H8A,H8B)
2.b Ternary CH refined with riding coordinates:
 C2(H2), C3(H3), C4(H4), C5(H5), C8(H8), C14(H14)
2.c Secondary CH2 refined with riding coordinates:
 C7(H7A,H7B), 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.d Aromatic/amide H refined with riding coordinates:
 C9(H9)
2.e Idealised Me refined as rotating group:
 C18(H18A,H18B,H18C), C19(H19A,H19B,H19C), C25(H25A,H25B,H25C)
;
_shelx_res_checksum              22978
_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 2.095
_oxdiff_exptl_absorpt_empirical_full_min 0.657