Design, Synthesis, and Anti-RNA Virus Activity of 6'-Fluorinated-Aristeromycin Analogues.
Yoon, Ji-Seong; Kim, Gyudong; Jarhad, Dnyandev B.; Kim, Hong-Rae; Shin, Young-Sup; Qu, Shuhao; Sahu, Pramod K.; Kim, Hea Ok; Lee, Hyuk Woo; Wang, Su Bin; Kong, Yun Jeong; Chang, Tong-Shin; Ogando, Natacha S.; Kovacikova, Kristina; Snijder, Eric J.; Posthuma, Clara C.; van Hemert, Martijn J.; Jeong, Lak Shin; Journal of medicinal chemistry 62 (2019) 6346–6362; doi:10.1021/acs.jmedchem.9b00781

data_1552560
_publ_section_title
;
 Design, Synthesis, and Anti-RNA Virus Activity of
 6'-Fluorinated-Aristeromycin Analogues.
;
_journal_issue                   13
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              6346
_journal_page_last               6362
_journal_paper_doi               10.1021/acs.jmedchem.9b00781
_journal_volume                  62
_journal_year                    2019
_chemical_absolute_configuration unk
_chemical_formula_moiety         'C10 H13 F N2 O5'
_chemical_formula_sum            'C10 H13 F N2 O5'
_chemical_formula_weight         260.22
_space_group_crystal_system      trigonal
_space_group_IT_number           154
_space_group_name_Hall           'P 32 2"'
_space_group_name_H-M_alt        'P 32 2 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     direct
_audit_creation_date             2016-10-25
_audit_creation_method
;
Olex2 1.2-ac21
(compiled 2015.09.16 svn.r134, GUI svn.r4998)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                120
_cell_formula_units_Z            6
_cell_length_a                   6.6465(2)
_cell_length_b                   6.6465(2)
_cell_length_c                   43.3632(14)
_cell_measurement_reflns_used    8995
_cell_measurement_temperature    295.71(13)
_cell_measurement_theta_max      75.9030
_cell_measurement_theta_min      3.0410
_cell_volume                     1658.97(9)
_computing_cell_refinement       'CrysAlisPro 1.171.38.44a (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.44a (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.44a (Rigaku OD, 2015)'
_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    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      air
_diffrn_ambient_temperature      295.71(13)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.4525
_diffrn_detector_type            AtlasS2
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.990
_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    -54.00  33.00   1.00    1.00    --  -41.49  38.00 120.00   87
  2  \w    -97.00 -61.00   1.00    1.00    --  -41.49-159.00  50.00   36
  3  \w   -115.00 -13.00   1.00    1.00    --  -41.49 -57.00 -30.00  102
  4  \w     39.00  86.00   1.00    1.00    --   41.49-118.00-156.00   47
  5  \w     38.00  74.00   1.00    1.00    --   41.49-125.00 -60.00   36
  6  \w     21.00  97.00   1.00    1.00    --   41.49  38.00 -90.00   76
  7  \w     44.00 130.00   1.00    2.47    --  112.00 -61.00 150.00   86
  8  \w     53.00 107.00   1.00    2.47    --  112.00 -61.00   0.00   54
  9  \w     85.00 173.00   1.00    2.47    --  112.00  30.00-120.00   88
 10  \w     40.00  67.00   1.00    2.47    --  112.00 -30.00 -30.00   27
 11  \w     86.00 139.00   1.00    2.47    --  112.00 -30.00 -30.00   53
 12  \w     37.00 113.00   1.00    2.47    --  112.00-111.00  30.00   76
 13  \w     83.00 150.00   1.00    2.47    --  112.00 178.00-150.00   67
 14  \w     55.00 116.00   1.00    2.47    --  112.00-111.00-120.00   61
 15  \w     72.00 103.00   1.00    2.47    --  112.00-111.00 -30.00   31
 16  \w     91.00 121.00   1.00    2.47    --  112.00 -45.00-120.00   30
 17  \w     84.00 111.00   1.00    2.47    --  112.00  30.00-180.00   27
 18  \w    115.00 153.00   1.00    2.47    --  112.00 111.00   0.00   38
 19  \w    139.00 171.00   1.00    2.47    --  112.00  30.00-180.00   32
 20  \w     85.00 165.00   1.00    2.47    --  112.00  30.00 -60.00   80
 21  \w     95.00 139.00   1.00    2.47    --  112.00 -77.00-150.00   44
 22  \w     47.00  85.00   1.00    2.47    --  112.00 -94.00 120.00   38
 23  \w    109.00 178.00   1.00    2.47    --  112.00  30.00 -30.00   69
 24  \w    141.00 175.00   1.00    2.47    --  112.00  77.00-180.00   34
 25  \w     40.00  78.00   1.00    2.47    --  112.00 -45.00-120.00   38
 26  \w     36.00 100.00   1.00    2.47    --  112.00-111.00-180.00   64
 27  \w    -58.00 -13.00   1.00    1.00    --  -41.49 -57.00  60.00   45
 28  \w    -54.00  32.00   1.00    1.00    --  -41.49  38.00  30.00   86
 29  \w     56.00  90.00   1.00    1.00    --   41.49-125.00   0.00   34
 30  \w     17.00  65.00   1.00    1.00    --   41.49  38.00 150.00   48
 31  \w     11.00  36.00   1.00    1.00    --   46.00  84.00-134.97   25
 32  \w     11.00  36.00   1.00    1.00    --   46.00  84.00 155.13   25
 33  \w     18.00  46.00   1.00    1.00    --   50.00  80.00  -0.64   28
 34  \w     20.00  45.00   1.00    1.00    --   54.00  81.00 -80.51   25
 35  \w     21.00  46.00   1.00    1.00    --   54.00  78.00  48.17   25
 36  \w     33.00  65.00   1.00    1.00    --   58.00  76.00 -83.57   32
 37  \w     26.00  52.00   1.00    1.00    --   58.00  76.00 -23.83   26
 38  \w     28.00  59.00   1.00    1.00    --   58.00  75.00-136.81   31
 39  \w    102.00 137.00   1.00    1.00    --   62.00  75.00  65.82   35
 40  \w     30.00  65.00   1.00    1.00    --   62.00  75.00  65.82   35
 41  \w     33.00  75.00   1.00    1.00    --   66.00  77.00 153.33   42
 42  \w     42.00  68.00   1.00    1.00    --   70.00  77.00 125.12   26
 43  \w     38.00  64.00   1.00    1.00    --   70.00  76.00  95.02   26
 44  \w     98.00 148.00   1.00    2.47    --   78.00  70.00  -8.22   50
 45  \w     47.00  92.00   1.00    2.47    --   78.00  70.00  -8.22   45
 46  \w     79.00 164.00   1.00    2.47    --  112.00  77.00  60.00   85
 47  \w     79.00 104.00   1.00    2.47    --  112.00  77.00-150.00   25
 48  \w    149.00 177.00   1.00    2.47    --  112.00  61.00 -30.00   28
 49  \w     83.00 109.00   1.00    2.47    --  112.00  61.00 -30.00   26
 50  \w    124.00 154.00   1.00    2.47    --  112.00  77.00 120.00   30
 51  \w     79.00 105.00   1.00    2.47    --  112.00  77.00 120.00   26
 52  \w     83.00 109.00   1.00    2.47    --  112.00  61.00 -90.00   26
 53  \w    144.00 170.00   1.00    2.47    --  112.00  61.00  60.00   26
 54  \w    119.00 171.00   1.00    2.47    --  112.00  77.00  30.00   52
 55  \w     79.00 167.00   1.00    2.47    --  112.00  77.00  90.00   88
 56  \w     83.00 110.00   1.00    2.47    --  112.00  61.00-180.00   27
 57  \w     80.00 106.00   1.00    2.47    --  112.00  77.00  30.00   26
 58  \w     79.00 121.00   1.00    2.47    --  112.00  77.00 -30.00   42
 59  \w     79.00 105.00   1.00    2.47    --  112.00  77.00-180.00   26
 60  \w     79.00 105.00   1.00    2.47    --  112.00  77.00 150.00   26
 61  \w    149.00 175.00   1.00    2.47    --  112.00  61.00 -60.00   26
 62  \w    140.00 166.00   1.00    2.47    --  112.00  61.00-150.00   26
 63  \w     83.00 109.00   1.00    2.47    --  112.00  61.00-150.00   26
 64  \w    116.00 141.00   1.00    2.47    --  112.00  77.00 150.00   25
 65  \w     85.00 111.00   1.00    2.47    --  112.00  61.00 -60.00   26
 66  \w     79.00 105.00   1.00    2.47    --  112.00  77.00 -90.00   26
 67  \w     83.00 128.00   1.00    2.47    --  112.00  61.00  30.00   45
 68  \w     86.00 129.00   1.00    2.47    --  112.00  61.00  60.00   43
 69  \w     84.00 110.00   1.00    2.47    --  112.00  61.00-120.00   26
 70  \w     79.00 105.00   1.00    2.47    --  112.00  77.00-120.00   26
 71  \w     79.00 159.00   1.00    2.47    --  112.00  77.00   0.00   80
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, AtlasS2'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.1427168000
_diffrn_orient_matrix_UB_12      0.2440979000
_diffrn_orient_matrix_UB_13      0.0141712000
_diffrn_orient_matrix_UB_21      -0.0931846000
_diffrn_orient_matrix_UB_22      -0.1011508000
_diffrn_orient_matrix_UB_23      0.0322329000
_diffrn_orient_matrix_UB_31      0.2063239000
_diffrn_orient_matrix_UB_32      -0.0414468000
_diffrn_orient_matrix_UB_33      0.0047722000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0654
_diffrn_reflns_av_unetI/netI     0.0230
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.990
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       54
_diffrn_reflns_limit_l_min       -54
_diffrn_reflns_number            29371
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.988
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         77.441
_diffrn_reflns_theta_min         6.123
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.183
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.81925
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.44a (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.563
_exptl_crystal_description       block
_exptl_crystal_F_000             816
_exptl_crystal_size_max          0.242
_exptl_crystal_size_mid          0.067
_exptl_crystal_size_min          0.034
_refine_diff_density_max         0.140
_refine_diff_density_min         -0.162
_refine_diff_density_rms         0.040
_refine_ls_abs_structure_details
;
 Flack x determined using 790 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.13(10)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.062
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     174
_refine_ls_number_reflns         2346
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.062
_refine_ls_R_factor_all          0.0337
_refine_ls_R_factor_gt           0.0309
_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^)+(0.0407P)^2^+0.2318P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0758
_refine_ls_wR_factor_ref         0.0779
_reflns_Friedel_coverage         0.595
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.984
_reflns_number_gt                2200
_reflns_number_total             2346
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            2g-CIF.cif
_cod_data_source_block           exp_531
_cod_original_cell_volume        1658.98(13)
_cod_database_code               1552560
_chemical_oxdiff_formula         C10O5N2F1H11
_reflns_odcompleteness_completeness 99.93
_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 O(H) groups
2.a Ternary CH refined with riding coordinates:
 C1'(H1'), C2'(H2'), C3'(H3'), C4'(H4')
2.b Secondary CH2 refined with riding coordinates:
 C5'(H5'A,H5'B)
2.c Aromatic/amide H refined with riding coordinates:
 C5(H5), C6(H6)
2.d Idealised tetrahedral OH refined as rotating group:
 O2'(H2'A), O3'(H3'A), O5'(H5')
;
_shelx_shelxl_version_number     2014/7
_olex2_date_sample_data_collection 2016-10-21
_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 3.437
_oxdiff_exptl_absorpt_empirical_full_min 0.635