Enzymatic synthesis of four stereoisomers of 3-substituted-4-hydroxypiperidines by carbonyl reductase-catalyzed reduction
Chen, Jing; Chen, Xi; Song, Jinsong; Zhang, Hongliu; Yang, Hongjiang; Feng, Jinhui; Wu, Qiaqing; Zhu, Dunming; RSC Advances 15 (2025) 21133–21141; doi:10.1039/D5RA02485D

data_7250593
_publ_section_title
;
 Enzymatic synthesis of four stereoisomers of
 3-substituted-4-hydroxypiperidines by carbonyl reductase-catalyzed
 reduction
;
_journal_issue                   26
_journal_name_full               'RSC Advances'
_journal_page_first              21133
_journal_page_last               21141
_journal_paper_doi               10.1039/D5RA02485D
_journal_volume                  15
_journal_year                    2025
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C16 H22 F N O3'
_chemical_formula_sum            'C16 H22 F N O3'
_chemical_formula_weight         295.356
_chemical_name_systematic        17
_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     iterative
_audit_block_doi                 10.5517/ccdc.csd.cc2mp04h
_audit_creation_date             2025-02-18
_audit_creation_method
;
Olex2 1.5
(compiled 2024.02.16 svn.r378c4104 for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2025-03-22 deposited with the CCDC.	2025-06-25 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.0869(1)
_cell_length_b                   12.3980(1)
_cell_length_c                   20.9757(3)
_cell_measurement_reflns_used    13369
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      74.1980
_cell_measurement_theta_min      4.1150
_cell_volume                     1582.94(4)
_computing_cell_refinement       'CrysAlisPro 1.171.42.102a (Rigaku OD, 2023)'
_computing_data_collection       'CrysAlisPro 1.171.42.102a (Rigaku OD, 2023)'
_computing_data_reduction        'CrysAlisPro 1.171.42.102a (Rigaku OD, 2023)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'olex2.refine 1.5 (Bourhis et al., 2015)'
_computing_structure_solution    'olex2.solve 1.5 (Bourhis et al., 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.00(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            'HyPix-Arc 150'
_diffrn_measured_fraction_theta_full 1.0000
_diffrn_measured_fraction_theta_max 0.9752
_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     61.00 107.00   0.50    0.05    --   54.52  30.00 120.00   92
  2  \w     85.00 131.00   0.50    0.05    --   78.29  30.00  30.00   92
  3  \w     72.00 118.00   0.50    0.05    --   65.77  30.00   0.00   92
  4  \w     92.00 138.00   0.50    0.05    --   85.54  30.00 -90.00   92
  5  \w     85.00 131.00   0.50    0.05    --   78.29  30.00-150.00   92
  6  \w     85.00 131.00   0.50    0.05    --   78.29  30.00-120.00   92
  7  \w     55.00 107.00   0.50    0.05    --   54.52  27.00 -35.00  104
  8  \w     86.00 138.00   0.50    0.05    --   85.54  27.00 -35.00  104
  9  \w     92.00 138.00   0.50    0.05    --   85.54  30.00   0.00   92
 10  \w     92.00 138.00   0.50    0.05    --   85.54  30.00 150.00   92
 11  \w     39.00  93.00   0.50    0.05    --   85.54-110.00  69.00  108
 12  \w     42.00  92.00   0.50    0.05    --   85.54 -95.00  90.00  100
 13  \w      9.00  69.00   0.50    0.05    --   54.52-104.00 -27.00  120
 14  \w     11.00  63.00   0.50    0.05    --   54.52 -95.00 -90.00  104
 15  \w     42.00  92.00   0.50    0.05    --   85.54 -95.00-150.00  100
 16  \w     33.00  92.00   0.50    0.05    --   78.29-104.00 -27.00  118
 17  \w     35.00  86.00   0.50    0.05    --   78.29 -95.00   0.00  102
 18  \w     11.00  63.00   0.50    0.05    --   54.52 -95.00  30.00  104
 19  \w     11.00  36.00   0.50    0.05    --   54.52 -95.00  90.00   50
 20  \w   -110.00 -65.00   0.50    0.05    --  -57.80 -30.00-150.00   90
 21  \w   -130.00 -85.00   0.50    0.05    --  -77.31 -30.00  30.00   90
 22  \w   -130.00 -85.00   0.50    0.05    --  -77.31 -30.00  60.00   90
 23  \w   -121.00 -76.00   0.50    0.05    --  -68.99 -30.00  90.00   90
 24  \w   -121.00 -76.00   0.50    0.05    --  -68.99 -30.00 120.00   90
 25  \w   -130.00 -80.00   0.50    0.05    --  -77.31 -27.00 161.00  100
 26  \w   -110.00 -61.00   0.50    0.05    --  -57.80 -27.00 161.00   98
 27  \w    -92.00 -31.00   0.50    0.05    --  -77.31 111.00 120.00  122
 28  \w    -87.00 -22.00   0.50    0.05    --  -68.99 110.00 164.00  130
 29  \w    -92.00 -31.00   0.50    0.05    --  -77.31 111.00  60.00  122
 30  \w    -92.00 -31.00   0.50    0.05    --  -77.31 111.00-120.00  122
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'ROD, Synergy Custom system, HyPix-Arc 150'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0429747000
_diffrn_orient_matrix_UB_12      -0.1092026000
_diffrn_orient_matrix_UB_13      -0.0327586000
_diffrn_orient_matrix_UB_21      -0.0781502000
_diffrn_orient_matrix_UB_22      -0.0475287000
_diffrn_orient_matrix_UB_23      0.0639525000
_diffrn_orient_matrix_UB_31      -0.2368863000
_diffrn_orient_matrix_UB_32      0.0354438000
_diffrn_orient_matrix_UB_33      -0.0151638000
_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  0.0348
_diffrn_reflns_av_unetI/netI     0.0189
_diffrn_reflns_Laue_measured_fraction_full 1.0000
_diffrn_reflns_Laue_measured_fraction_max 0.9752
_diffrn_reflns_limit_h_max       5
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       26
_diffrn_reflns_limit_l_min       -25
_diffrn_reflns_number            17980
_diffrn_reflns_point_group_measured_fraction_full 0.9972
_diffrn_reflns_point_group_measured_fraction_max 0.9507
_diffrn_reflns_theta_full        67.6840
_diffrn_reflns_theta_max         74.50
_diffrn_reflns_theta_min         4.14
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.767
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.84002
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.102a (Rigaku Oxford Diffraction, 2023)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.239
_exptl_crystal_description       block
_exptl_crystal_F_000             634.290
_exptl_crystal_preparation       'single crystal'
_exptl_crystal_recrystallization_method 'vapor diffusion'
_exptl_crystal_size_max          0.1
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.1224
_refine_diff_density_min         -0.1718
_refine_diff_density_rms         0.0339
_refine_ls_abs_structure_details
'Hooft, R.W.W., Straver, L.H., Spek, A.L. (2010). J. Appl. Cryst., 43, 665-668.'
_refine_ls_abs_structure_Flack   -0.02(4)
_refine_ls_d_res_high            0.8000
_refine_ls_d_res_low             10.6730
_refine_ls_goodness_of_fit_ref   1.0381
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_constraints    35
_refine_ls_number_parameters     194
_refine_ls_number_reflns         3083
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.0381
_refine_ls_R_factor_all          0.0306
_refine_ls_R_factor_gt           0.0293
_refine_ls_shift/su_max          0.0003
_refine_ls_shift/su_mean         0.0000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0511P)^2^+0.1634P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0778
_refine_ls_wR_factor_ref         0.0787
_reflns_Friedel_coverage         0.916
_reflns_limit_h_max              7
_reflns_limit_h_min              -7
_reflns_limit_k_max              15
_reflns_limit_k_min              -15
_reflns_limit_l_max              26
_reflns_limit_l_min              -25
_reflns_number_gt                2959
_reflns_number_total             3083
_reflns_threshold_expression     I>=2u(I)
_cod_data_source_file            d5ra02485d2.cif
_cod_data_source_block           17xia_auto
_cod_original_sg_symbol_Hall     ' P 2ac 2ab'
_cod_database_code               7250593
_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, All O(H) groups
2.a Ternary CH refined with riding coordinates:
 C009(H009), C00B(H00B)
2.b Secondary CH2 refined with riding coordinates:
 C00C(H00a,H00c), C00F(H00f,H00g), C00G(H00h,H00i)
2.c Aromatic/amide H refined with riding coordinates:
 C008(H008), C00D(H00D), C00E(H00E), C00H(H00j)
2.d Idealised Me refined as rotating group:
 C00J(H00k,H00l,H00m), C00K(H00n,H00o,H00p), C00L(H00q,H00r,H00s)
2.e Idealised tetrahedral OH refined as rotating group:
 O004(H004)
;
_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 2.926
_oxdiff_exptl_absorpt_empirical_full_min 0.649