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_1552562
_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 H12 F2 N2 O5'
_chemical_formula_sum            'C10 H12 F2 N2 O5'
_chemical_formula_weight         278.21
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_symmetry_Int_Tables_number      19
_atom_sites_solution_primary     dual
_audit_creation_date             2018-04-19
_audit_creation_method
;
Olex2 1.2
(compiled 2018.04.03 svn.r3497 for OlexSys, GUI svn.r5486)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   5.8735(2)
_cell_length_b                   13.5166(5)
_cell_length_c                   14.1374(5)
_cell_measurement_reflns_used    2846
_cell_measurement_temperature    293.55(10)
_cell_measurement_theta_max      73.5320
_cell_measurement_theta_min      3.1200
_cell_volume                     1122.36(7)
_computing_cell_refinement       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'olex2.refine (Bourhis et al., 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      air
_diffrn_ambient_temperature      293.55(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.2262
_diffrn_detector_type            AtlasS2
_diffrn_measured_fraction_theta_full 0.9652
_diffrn_measured_fraction_theta_max 0.9652
_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    -65.00  30.00   0.50    1.02    --  -41.49  57.00 -30.00  190
  2  \w      1.00  79.00   0.50    1.02    --   41.49 -99.00  60.00  156
  3  \w     45.00  82.00   0.50    1.02    --   41.49-125.00 -60.00   74
  4  \w     94.00 124.00   0.50    4.08    --  106.19 125.00-150.00   60
  5  \w     95.00 170.00   0.50    4.08    --  106.19 125.00 120.00  150
  6  \w     43.00 122.00   0.50    4.08    --  106.19 -61.00-180.00  158
  7  \w    102.00 167.00   0.50    4.08    --  106.19 125.00 -60.00  130
  8  \w     26.00 139.00   0.50    4.08    --  106.19 -15.00 150.00  226
;
_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      0.2214850000
_diffrn_orient_matrix_UB_12      -0.0353130000
_diffrn_orient_matrix_UB_13      0.0476993000
_diffrn_orient_matrix_UB_21      -0.1029912000
_diffrn_orient_matrix_UB_22      -0.1040110000
_diffrn_orient_matrix_UB_23      0.0122954000
_diffrn_orient_matrix_UB_31      0.0956238000
_diffrn_orient_matrix_UB_32      -0.0304657000
_diffrn_orient_matrix_UB_33      -0.0971764000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0191
_diffrn_reflns_av_unetI/netI     0.0258
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       11
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            3965
_diffrn_reflns_theta_full        73.6588
_diffrn_reflns_theta_max         73.66
_diffrn_reflns_theta_min         4.53
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.343
_exptl_absorpt_correction_T_max  0.976
_exptl_absorpt_correction_T_min  0.945
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.41 (Rigaku Oxford Diffraction, 2015)
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            'translucent light yellow'
_exptl_crystal_density_diffrn    1.6463
_exptl_crystal_description       irregular
_exptl_crystal_F_000             578.5867
_exptl_crystal_size_max          0.261
_exptl_crystal_size_mid          0.21
_exptl_crystal_size_min          0.074
_refine_diff_density_max         0.1706
_refine_diff_density_min         -0.1851
_refine_diff_density_rms         0.0409
_refine_ls_abs_structure_details
'Flack, H. D. (1983). Acta Cryst. A39, 876-881.'
_refine_ls_abs_structure_Flack   0.02(13)
_refine_ls_d_res_high            0.8034
_refine_ls_d_res_low             9.7698
_refine_ls_goodness_of_fit_ref   1.0649
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_constraints    23
_refine_ls_number_parameters     175
_refine_ls_number_reflns         2190
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.0649
_refine_ls_R_factor_all          0.0318
_refine_ls_R_factor_gt           0.0307
_refine_ls_shift/su_max          0.0000
_refine_ls_shift/su_mean         0.0000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0406P)^2^+0.2159P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0803
_refine_ls_wR_factor_ref         0.0813
_reflns_Friedel_coverage         0.947
_reflns_limit_h_max              7
_reflns_limit_h_min              -7
_reflns_limit_k_max              16
_reflns_limit_k_min              -16
_reflns_limit_l_max              17
_reflns_limit_l_min              -16
_reflns_number_gt                2111
_reflns_number_total             2190
_reflns_threshold_expression     I>=2u(I)
_cod_data_source_file            2h-CIF.cif
_cod_data_source_block           exp_1200
_cod_original_sg_symbol_Hall     ' P 2ac 2ab'
_cod_database_code               1552562
_chemical_oxdiff_formula         'C10 H12 F2 N2 O5'
_chemical_oxdiff_usercomment     DIF-U
_reflns_odcompleteness_completeness 99.92
_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, All N(H) groups
 At 1.5 times of:
  All O(H) groups
2.a Ternary CH refined with riding coordinates:
 C7(H7), C11(H11), C10(H10), C9(H9)
2.b Secondary CH2 refined with riding coordinates:
 C14(H14a,H14b)
2.c Aromatic/amide H refined with riding coordinates:
 N3(H3), C6(H6), C5(H5)
2.d Idealised tetrahedral OH refined as rotating group:
 O16(H16), O17(H17), O15(H15)
;
_olex2_date_sample_data_collection 2018-04-18
_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 1.355
_oxdiff_exptl_absorpt_empirical_full_min 0.701