Stereoselective synthesis of novel adamantane derivatives with high potency against rimantadine-resistant influenza A virus strains.
Kuznetsov, Nikolai Yu; Tikhov, Rabdan M.; Godovikov, Ivan A.; Medvedev, Michael G.; Lyssenko, Konstantin A.; Burtseva, Elena I.; Kirillova, Elena S.; Bubnov, Yuri N.; Organic & biomolecular chemistry 15 (2017) 3152–3157; doi:10.1039/c7ob00331e

data_7155529
_publ_section_title
;
 Stereoselective synthesis of novel adamantane derivatives with high
 potency against rimantadine-resistant influenza A virus strains.
;
_journal_issue                   15
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              3152
_journal_page_last               3157
_journal_paper_doi               10.1039/c7ob00331e
_journal_volume                  15
_journal_year                    2017
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C19 H31 N O2'
_chemical_formula_sum            'C19 H31 N O2'
_chemical_formula_weight         305.45
_chemical_name_systematic
'tert-butyl (1-((3r,5r,7r)-adamantan-1-yl)but-3-en-1-yl)carbamate'
_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'
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   mixed
_audit_creation_date             2015-12-04
_audit_creation_method
;
Olex2 1.2
(compiled 2015.09.30 svn.r3233 for OlexSys, GUI svn.r5103)
;
_audit_update_record
;
2015-12-04 deposited with the CCDC.
2017-03-09 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 96.0380(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   10.3207(2)
_cell_length_b                   17.1680(4)
_cell_length_c                   10.4198(2)
_cell_measurement_reflns_used    9974
_cell_measurement_temperature    120
_cell_measurement_theta_max      67.532
_cell_measurement_theta_min      4.266
_cell_volume                     1836.00(7)
_computing_cell_refinement       'SAINT v8.27A (Bruker, 2012)'
_computing_data_reduction        'SAINT v8.27A (Bruker, 2012)'
_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    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_temperature      120
_diffrn_detector                 'Bruker APEX2 area detector'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            'CCD area detector'
_diffrn_measured_fraction_theta_full 0.968
_diffrn_measured_fraction_theta_max 0.967
_diffrn_measurement_device       'three-circle diffractometer'
_diffrn_measurement_device_type  'Bruker APEX-DUO CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  'mirror optics'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0209
_diffrn_reflns_av_unetI/netI     0.0162
_diffrn_reflns_Laue_measured_fraction_full 0.968
_diffrn_reflns_Laue_measured_fraction_max 0.967
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -19
_diffrn_reflns_limit_l_max       11
_diffrn_reflns_limit_l_min       -12
_diffrn_reflns_number            28420
_diffrn_reflns_point_group_measured_fraction_full 0.938
_diffrn_reflns_point_group_measured_fraction_max 0.937
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         67.688
_diffrn_reflns_theta_min         4.267
_diffrn_source                   'microfocus sealed X-ray tube'
_diffrn_source_type              'Incoatec I\ms'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.547
_exptl_absorpt_correction_T_max  0.7530
_exptl_absorpt_correction_T_min  0.6703
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2008/1 (Bruker,2008) was used for absorption correction.
wR2(int) was 0.1318 before and 0.0364 after correction.
The Ratio of minimum to maximum transmission is 0.8902.
The \l/2 correction factor is 0.0000.
;
_exptl_crystal_colour            white
_exptl_crystal_colour_primary    white
_exptl_crystal_density_diffrn    1.105
_exptl_crystal_description       needle
_exptl_crystal_F_000             672
_exptl_crystal_size_max          0.5
_exptl_crystal_size_mid          0.03
_exptl_crystal_size_min          0.03
_refine_diff_density_max         0.198
_refine_diff_density_min         -0.180
_refine_diff_density_rms         0.036
_refine_ls_abs_structure_details
;
 Flack x determined using 2832 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.04(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.058
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     411
_refine_ls_number_reflns         6252
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.058
_refine_ls_R_factor_all          0.0326
_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^)+(0.0510P)^2^+0.4600P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0897
_refine_ls_wR_factor_ref         0.0900
_reflns_Friedel_coverage         0.870
_reflns_Friedel_fraction_full    0.906
_reflns_Friedel_fraction_max     0.905
_reflns_number_gt                6171
_reflns_number_total             6252
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c7ob00331e2.cif
_cod_data_source_block           a
_cod_depositor_comments
'Adding full bibliography for 7155527--7155531.cif.'
_cod_database_code               7155529
_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:
 C9(H9), C9A(H9A), C17(H17), C17A(H17A), C19(H19), C19A(H19A), C21(H21),
 C21A(H21A)
2.b Secondary CH2 refined with riding coordinates:
 C10(H10A,H10B), C10A(H10C,H10D), C14(H14A,H14B), C14A(H14C,H14D), C15(H15A,
 H15B), C15A(H15C,H15D), C16(H16A,H16B), C16A(H16D,H16C), C18(H18A,H18B),
 C18A(H18C,H18D), C20(H20A,H20B), C20A(H20C,H20D), C22(H22B,H22A), C22A(H22C,
 H22D)
2.c Aromatic/amide H refined with riding coordinates:
 C11(H11), C11A(H11A)
2.d X=CH2 refined with riding coordinates:
 C12(H12A,H12B), C12A(H12D,H12C)
2.e Idealised Me refined as rotating group:
 C1(H1A,H1B,H1C), C1A(H1AA,H1AB,H1AC), C2(H2A,H2B,H2C), C2A(H2AA,H2AB,H2AC),
 C3(H3A,H3B,H3C), C3A(H3AA,H3AB,H3AC)
;
_shelx_res_checksum              27776
_shelx_shelxl_version_number     2014/7
_olex2_computing_structure_refinement_long 'ShelXL (Sheldrick, 2008)'
_olex2_computing_structure_solution_long 'ShelXS (Sheldrick, 2008)'
_olex2_exptl_crystal_mounting_method 'on a glass needle'
_olex2_submission_original_sample_id RT-109
_olex2_submission_special_instructions 'No special instructions were received'