Enzymatic- and Iridium-Catalyzed Asymmetric Synthesis of a Benzothiazepinylphosphonate Bile Acid Transporter Inhibitor
David J. Cowan; Jon L. Collins; Mark B. Mitchell; John A. Ray; Peter W. Sutton; Amy A. Sarjeant; Eric E. Boros; Journal of Organic Chemistry 78 (2013) 12726–12734; doi:10.1021/jo402311e

data_4028883
_publ_section_title
;
 Enzymatic- and Iridium-Catalyzed Asymmetric Synthesis of a
 Benzothiazepinylphosphonate Bile Acid Transporter Inhibitor
;
_journal_name_full               'Journal of Organic Chemistry'
_journal_page_first              12726
_journal_page_last               12734
_journal_paper_doi               10.1021/jo402311e
_journal_volume                  78
_journal_year                    2013
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C27 H40 N O6 P S'
_chemical_formula_sum            'C27 H40 N O6 P S'
_chemical_formula_weight         537.63
_chemical_name_systematic
;
(3R,5R)-3-butyl-8-(diethoxyphosphorylmethyl)-3-ethyl-7-methoxy-5-
phenyl-4,5-dihydro-2H-benzo[f][1,4]thiazepine 1,1-dioxide 
;
_space_group_IT_number           4
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_date             2011-07-22
_audit_creation_method
;
  Olex2 1.1
  (compiled 2011.02.15 svn.r1672, GUI svn.r3494)
;
_cell_angle_alpha                90.00
_cell_angle_beta                 108.807(4)
_cell_angle_gamma                90.00
_cell_formula_units_Z            2
_cell_length_a                   12.3598(7)
_cell_length_b                   8.2062(6)
_cell_length_c                   14.7005(9)
_cell_measurement_reflns_used    3441
_cell_measurement_temperature    99.97
_cell_measurement_theta_max      63.87
_cell_measurement_theta_min      3.18
_cell_volume                     1411.42(16)
_computing_cell_refinement       'SAINT V7.23A (Bruker, 2005)'
_computing_data_collection       'APEX2 V2.1-4 (Bruker, 2007)'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics
;
O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H. Puschmann,
OLEX2: a complete structure solution, refinement and analysis program.
J. Appl. Cryst. (2009). 42, 339-341.
;
_computing_publication_material
;
O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H. Puschmann,
OLEX2: a complete structure solution, refinement and analysis program.
J. Appl. Cryst. (2009). 42, 339-341.
;
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 2008)'
_computing_structure_solution
'A short history of SHELX (Sheldrick, 2007)/Bruker'
_diffrn_ambient_temperature      99.97
_diffrn_detector_area_resol_mean 8
_diffrn_measured_fraction_theta_full 0.973
_diffrn_measured_fraction_theta_max 0.973
_diffrn_measurement_device_type  'Bruker SMART APEX CCD area detector'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  'Quazar optics'
_diffrn_radiation_source         microsource
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0652
_diffrn_reflns_av_unetI/netI     0.0747
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            8916
_diffrn_reflns_theta_full        64.24
_diffrn_reflns_theta_max         64.24
_diffrn_reflns_theta_min         3.18
_diffrn_source_current           0.64
_diffrn_source_power             0.028608
_diffrn_source_voltage           44.7
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    1.885
_exptl_absorpt_correction_T_max  0.7525
_exptl_absorpt_correction_T_min  0.5436
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
 SADABS-2008/1 (Bruker,2008) was used for absorption correction.
 R(int) was 0.0936 before and 0.0567 after correction.
 The Ratio of minimum to maximum transmission is 0.722392026578.
 The \l/2 correction factor is 0.0015
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.265
_exptl_crystal_description       plate
_exptl_crystal_F_000             576
_exptl_crystal_size_max          0.268
_exptl_crystal_size_mid          0.119
_exptl_crystal_size_min          0.01
_refine_diff_density_max         0.399
_refine_diff_density_min         -0.235
_refine_diff_density_rms         0.058
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.01(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.035
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     334
_refine_ls_number_reflns         4120
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.035
_refine_ls_R_factor_all          0.0725
_refine_ls_R_factor_gt           0.0559
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0741P)^2^+0.4958P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1318
_refine_ls_wR_factor_ref         0.1419
_reflns_number_gt                3380
_reflns_number_total             4120
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            jo402311e_si_001.cif
_cod_data_source_block           31476
_cod_database_code               4028883
_local_nu_authors                'Dr. Amy A. Sarjeant'
_local_nu_crystal_method         'slow cooling'
_local_nu_crystal_solvent        heptanes
_local_nu_labbook_chem           N1622-68-1
_local_nu_labbook_crystalization N1622-68-1
_local_nu_labbook_xray           NUGSK01_030
_local_nu_project_code           17403
_local_nu_project_name           unknown
_local_nu_quality_factor         2
_local_nu_refine_ls_disord_occ   n/a
_local_nu_refine_ls_disord_u     n/a
_local_nu_refine_ls_disord_xyz   n/a
_local_nu_refine_ls_h_carbon_u   riding
_local_nu_refine_ls_h_carbon_xyz riding
_local_nu_refine_ls_h_hetero_u   'freely refined'
_local_nu_refine_ls_h_hetero_xyz 'freely refined'
_local_nu_refine_ls_nonh_u       anisotropic
_local_nu_refine_ls_nonh_xyz     'freely refined'
_local_nunumber                  GSK2794585A
_local_xraynumber                31476