Enantioselective Total Synthesis of Nigelladine A via Late-Stage C-H Oxidation Enabled by an Engineered P450 Enzyme.
Loskot, Steven A.; Romney, David K.; Arnold, Frances H.; Stoltz, Brian M.; Journal of the American Chemical Society 139 (2017) 10196–10199; doi:10.1021/jacs.7b05196

data_4131420
_publ_section_title
;
 Enantioselective Total Synthesis of Nigelladine A via Late-Stage C-H
 Oxidation Enabled by an Engineered P450 Enzyme.
;
_journal_issue                   30
_journal_name_full               'Journal of the American Chemical Society'
_journal_page_first              10196
_journal_page_last               10199
_journal_paper_doi               10.1021/jacs.7b05196
_journal_volume                  139
_journal_year                    2017
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C24 H37 N O3'
_chemical_formula_sum            'C24 H37 N O3'
_chemical_formula_weight         387.54
_space_group_crystal_system      triclinic
_space_group_IT_number           1
_space_group_name_Hall           'P 1'
_space_group_name_H-M_alt        'P 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_audit_creation_date             2016-06-27
_audit_creation_method
;
Olex2 1.2
(compiled 2016.02.19 svn.r3266 for OlexSys, GUI svn.r5155),
 SHELXL-2014,
 and manual edit
;
_cell_angle_alpha                89.402(8)
_cell_angle_beta                 77.360(8)
_cell_angle_gamma                89.745(8)
_cell_formula_units_Z            2
_cell_length_a                   9.6892(11)
_cell_length_b                   10.0478(9)
_cell_length_c                   11.9882(11)
_cell_measurement_reflns_used    9539
_cell_measurement_temperature    100
_cell_measurement_theta_max      77.49
_cell_measurement_theta_min      3.78
_cell_volume                     1138.8(2)
_computing_cell_refinement       'SAINT V8.37A (Bruker-AXS, 2007)'
_computing_data_collection       'APEX2 2016.1-0 (Bruker-AXS, 2007)'
_computing_data_reduction        'SAINT V8.37A (Bruker-AXS, 2007)'
_computing_molecular_graphics    'DIAMOND 3 (Crystal Impact, 1999)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL-2014/7 (Sheldrick, 2014)'
_computing_structure_solution    'XT-2014/4 (Sheldrick, 2012)'
_diffrn_ambient_temperature      100
_diffrn_detector                 'CMOS Area Detector'
_diffrn_detector_area_resol_mean 10.24
_diffrn_detector_type            'Bruker PHOTON 100 CMOS'
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.985
_diffrn_measurement_device       '\k-geometry diffractometer'
_diffrn_measurement_device_type  'Bruker D8 VENTURE Kappa Duo PHOTON 100 CMOS'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  'multilayer mirrors'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0587
_diffrn_reflns_av_unetI/netI     0.0429
_diffrn_reflns_Laue_measured_fraction_full 0.996
_diffrn_reflns_Laue_measured_fraction_max 0.985
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            44144
_diffrn_reflns_point_group_measured_fraction_full 0.954
_diffrn_reflns_point_group_measured_fraction_max 0.927
_diffrn_reflns_theta_full        67.000
_diffrn_reflns_theta_max         79.188
_diffrn_reflns_theta_min         3.779
_diffrn_source                   'I\mS HB micro-focus sealed tube'
_diffrn_source_current           1
_diffrn_source_power             0.05
_diffrn_source_type              'Incoatech I\mS HB'
_diffrn_source_voltage           50
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.574
_exptl_absorpt_correction_T_max  0.9470
_exptl_absorpt_correction_T_min  0.8656
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2014/5 (Bruker,2014/5) was used for absorption correction. wR2(int) was 0.1121 before and 0.0869 after correction. The Ratio of minimum to maximum transmission is 0.9140. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.130
_exptl_crystal_description       wedge
_exptl_crystal_F_000             424
_exptl_crystal_size_max          0.31
_exptl_crystal_size_mid          0.15
_exptl_crystal_size_min          0.15
_refine_diff_density_max         0.318
_refine_diff_density_min         -0.238
_refine_diff_density_rms         0.049
_refine_ls_abs_structure_details
;
 Flack x determined using 3496 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.08(8)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.062
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     521
_refine_ls_number_reflns         9136
_refine_ls_number_restraints     3
_refine_ls_restrained_S_all      1.062
_refine_ls_R_factor_all          0.0568
_refine_ls_R_factor_gt           0.0497
_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^)+(0.0340P)^2^+0.7081P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1066
_refine_ls_wR_factor_ref         0.1114
_reflns_Friedel_coverage         0.882
_reflns_Friedel_fraction_full    0.912
_reflns_Friedel_fraction_max     0.869
_reflns_number_gt                8351
_reflns_number_total             9136
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ja7b05196_si_002.cif
_cod_data_source_block           p16232
_cod_original_cell_volume        1138.76(19)
_cod_database_code               4131420
_shelx_estimated_absorpt_t_max   0.919
_shelx_estimated_absorpt_t_min   0.842
_refine_ls_abs_structure_hooft   0.14(7)
_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 C(H,H,H) groups
2.a Ternary CH refined with riding coordinates:
 C11(H11), C11B(H11B)
2.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C3(H3A,H3B), C9(H9A,H9B), C16(H16A,H16B), C2B(H2BA,H2BB),
 C3B(H3BA,H3BB), C9B(H9BA,H9BB), C16B(H16C,H16D)
2.c Aromatic/amide H refined with riding coordinates:
 N1(H1), C5(H5), N1B(H1B), C5B(H5B)
2.d X=CH2 refined with riding coordinates:
 C15(H15A,H15B), C15B(H15C,H15D)
2.e Idealised Me refined as rotating group:
 C10(H10A,H10B,H10C), C12(H12A,H12B,H12C), C13(H13A,H13B,H13C), C18(H18A,H18B,
 H18C), C19(H19A,H19B,H19C), C22(H22A,H22B,H22C), C23(H23A,H23B,H23C), C24(H24A,
 H24B,H24C), C10B(H10D,H10E,H10F), C12B(H12D,H12E,H12F), C13B(H13D,H13E,H13F),
 C18B(H18D,H18E,H18F), C19B(H19D,H19E,H19F), C22B(H22D,H22E,H22F), C23B(H23D,
 H23E,H23F), C24B(H24D,H24E,H24F)
;
_shelx_shelxl_version_number     2014/7
_olex2_submission_special_instructions 'No special instructions were received'