Design, Synthesis, and Biological Evaluation of Structurally Rigid Analogues of 4-(3-Hydroxyphenyl)piperidine Opioid Receptor Antagonists.
Runyon, Scott P.; Kormos, Chad M.; Gichinga, Moses G.; Mascarella, S. Wayne; Navarro, Hernán A; Deschamps, Jeffrey R.; Imler, Gregory H.; Carroll, F. Ivy; The Journal of organic chemistry 81 (2016) 10383–10391; doi:10.1021/acs.joc.6b01366

data_4037051
_publ_section_title
;
 Design, Synthesis, and Biological Evaluation of Structurally Rigid
 Analogues of 4-(3-Hydroxyphenyl)piperidine Opioid Receptor Antagonists.
;
_journal_issue                   21
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              10383
_journal_page_last               10391
_journal_paper_doi               10.1021/acs.joc.6b01366
_journal_volume                  81
_journal_year                    2016
_chemical_absolute_configuration rm
_chemical_formula_sum            'C20 H29 N O7'
_chemical_formula_weight         395.44
_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
_audit_creation_method           SHELXL-2014/7
_cell_angle_alpha                90
_cell_angle_beta                 97.549(2)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   7.5585(2)
_cell_length_b                   7.1426(2)
_cell_length_c                   19.8360(5)
_cell_measurement_reflns_used    3886
_cell_measurement_temperature    218(2)
_cell_measurement_theta_max      28.34
_cell_measurement_theta_min      2.72
_cell_volume                     1061.61(5)
_computing_cell_refinement       'Bruker SMART v5.631 (Bruker, 2001)'
_computing_data_collection       'Bruker SMART v5.631 (Bruker, 2001)'
_computing_data_reduction
;
Bruker SAINT v6.45A (Bruker, 2002), Bruker XPREP v6.14 (Bruker, 2001)
;
_computing_molecular_graphics    'Bruker SHELXTL v6.14 (Bruker, 2000b)'
_computing_publication_material  'Bruker SHELXTL v6.14 (Bruker, 2000b)'
_computing_structure_refinement  'Bruker SHELXTL v6.14 (Bruker, 2000b)'
_computing_structure_solution    'Bruker SHELXTL v6.14 (Bruker, 2000b)'
_diffrn_ambient_temperature      218(2)
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_device_type  'Bruker APEX 2 CCD'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'sealed tube'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0280
_diffrn_reflns_av_unetI/netI     0.0464
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       26
_diffrn_reflns_limit_l_min       -26
_diffrn_reflns_number            12296
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.981
_diffrn_reflns_theta_full        25.000
_diffrn_reflns_theta_max         29.009
_diffrn_reflns_theta_min         1.035
_exptl_absorpt_coefficient_mu    0.093
_exptl_absorpt_correction_T_max  0.7458
_exptl_absorpt_correction_T_min  0.6856
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS v2.10 (Bruker, 2000c)'
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.237
_exptl_crystal_description       plate
_exptl_crystal_F_000             424
_exptl_crystal_size_max          0.205
_exptl_crystal_size_mid          0.143
_exptl_crystal_size_min          0.025
_refine_diff_density_max         0.308
_refine_diff_density_min         -0.502
_refine_diff_density_rms         0.108
_refine_ls_abs_structure_details
;
Flack x determined using 1673 quotients [(I+)-(I-)]/[(I+)+(I-)]
(Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).

Absolute configuration set using a reference molecule. Absolute configyration as 
reported by PLATON, C1' =  S, C2' = S, and C6' = S. C2" and C3" (from reference
molecule set to the known R,R configuration.
;
_refine_ls_abs_structure_Flack   0.9(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.094
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     287
_refine_ls_number_reflns         5549
_refine_ls_number_restraints     28
_refine_ls_restrained_S_all      1.093
_refine_ls_R_factor_all          0.0681
_refine_ls_R_factor_gt           0.0463
_refine_ls_shift/su_max          0.091
_refine_ls_shift/su_mean         0.008
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0722P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1086
_refine_ls_wR_factor_ref         0.1280
_reflns_Friedel_coverage         0.827
_reflns_Friedel_fraction_full    0.994
_reflns_Friedel_fraction_max     0.962
_reflns_number_gt                4488
_reflns_number_total             5549
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo6b01366_si_002.cif
_cod_data_source_block           rti109z
_cod_original_sg_symbol_H-M      'P 21'
_cod_database_code               4037051
_shelx_shelxl_version_number     2014/7
_shelx_estimated_absorpt_t_min   0.981
_shelx_estimated_absorpt_t_max   0.998
_shelx_res_checksum              24490
_shelx_hkl_checksum              83735