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_7250590
_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_formula_moiety         'C16 H23 N O3'
_chemical_formula_sum            'C16 H23 N O3'
_chemical_formula_weight         277.35
_chemical_name_systematic        0320-6
_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
_atom_sites_solution_primary     iterative
_audit_block_doi                 10.5517/ccdc.csd.cc2db89b
_audit_creation_date             2024-03-20
_audit_creation_method
;
Olex2 1.5
(compiled 2024.02.16 svn.r378c4104 for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2025-02-13 deposited with the CCDC.	2025-06-25 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 101.430(5)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   5.7962(3)
_cell_length_b                   9.4231(4)
_cell_length_c                   13.7625(6)
_cell_measurement_reflns_used    11291
_cell_measurement_temperature    100.01(10)
_cell_measurement_theta_max      73.5110
_cell_measurement_theta_min      3.1870
_cell_volume                     736.77(6)
_computing_cell_refinement       'CrysAlisPro 1.171.41.122a (Rigaku OD, 2021)'
_computing_data_collection       'CrysAlisPro 1.171.41.122a (Rigaku OD, 2021)'
_computing_data_reduction        'CrysAlisPro 1.171.41.122a (Rigaku OD, 2021)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2019/3 (Sheldrick, 2015)'
_computing_structure_solution    'olex2.solve 1.5 (Bourhis et al., 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.01(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 1.000
_diffrn_measured_fraction_theta_max 0.967
_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    0.10    --   54.36  30.00 -30.00   92
  2  \w     85.00 131.00   0.50    0.10    --   78.20  30.00-180.00   92
  3  \w     61.00 107.00   0.50    0.10    --   54.36  30.00-120.00   92
  4  \w     85.00 131.00   0.50    0.10    --   78.20  30.00 -90.00   92
  5  \w     92.00 138.00   0.50    0.10    --   85.54  30.00   0.00   92
  6  \w     61.00 107.00   0.50    0.10    --   54.36  30.00   0.00   92
  7  \w     61.00  93.00   0.50    0.10    --   54.36  30.00  30.00   64
  8  \w     72.00 118.00   0.50    0.10    --   65.53  30.00  90.00   92
  9  \w     92.00 138.00   0.50    0.10    --   85.54  30.00 120.00   92
 10  \w     48.00 133.00   0.50    0.10    --   85.54  15.00  90.00  170
 11  \w     29.00  97.00   0.50    0.10    --   78.20-111.00 150.00  136
 12  \w     22.00  74.00   0.50    0.10    --   65.53 -95.00 150.00  104
 13  \w     29.00  97.00   0.50    0.10    --   78.20-111.00 120.00  136
 14  \w     42.00  93.00   0.50    0.10    --   85.54 -95.00  30.00  102
 15  \w     42.00  93.00   0.50    0.10    --   85.54 -95.00 -90.00  102
 16  \w     42.00  93.00   0.50    0.10    --   85.54 -95.00-135.00  102
 17  \w     42.00  93.00   0.50    0.10    --   85.54 -95.00-180.00  102
 18  \w     11.00  62.00   0.50    0.10    --   54.36 -95.00-135.00  102
 19  \w     22.00  74.00   0.50    0.10    --   65.53 -95.00-135.00  104
 20  \w     35.00  86.00   0.50    0.10    --   78.20 -95.00-135.00  102
 21  \w     11.00  62.00   0.50    0.10    --   54.36 -95.00 -60.00  102
 22  \w     11.00  62.00   0.50    0.10    --   54.36 -95.00 120.00  102
 23  \w     11.00  62.00   0.50    0.10    --   54.36 -95.00  90.00  102
 24  \w    -85.00 -34.00   0.50    0.10    --  -77.27  95.00 -25.00  102
 25  \w    -96.00 -33.00   0.50    0.10    --  -82.00 111.00-120.00  126
 26  \w    -97.00 -28.00   0.50    0.10    --  -77.27 111.00 -90.00  138
 27  \w    -97.00 -28.00   0.50    0.10    --  -77.27 111.00-150.00  138
 28  \w    -97.00 -28.00   0.50    0.10    --  -77.27 111.00 -60.00  138
 29  \w    -90.00 -38.00   0.50    0.10    --  -82.00  95.00 -25.00  104
 30  \w    -66.00 -14.00   0.50    0.10    --  -57.83  95.00 -25.00  104
 31  \w    -77.00 -25.00   0.50    0.10    --  -69.06  95.00 -25.00  104
 32  \w    -96.00 -33.00   0.50    0.10    --  -82.00 111.00   0.00  126
 33  \w    -98.00 -20.00   0.50    0.10    --  -69.06 125.00   0.00  156
 34  \w    -97.00 -28.00   0.50    0.10    --  -77.27 111.00 120.00  138
 35  \w   -109.00 -38.00   0.50    0.10    --  -57.83 -15.00 -90.00  142
 36  \w   -130.00 -85.00   0.50    0.10    --  -77.27 -30.00-120.00   90
 37  \w   -130.00 -85.00   0.50    0.10    --  -77.27 -30.00 -90.00   90
 38  \w   -134.00 -89.00   0.50    0.10    --  -82.00 -30.00-150.00   90
 39  \w   -134.00 -89.00   0.50    0.10    --  -82.00 -30.00 -60.00   90
 40  \w   -130.00 -85.00   0.50    0.10    --  -77.27 -30.00   0.00   90
 41  \w   -110.00 -65.00   0.50    0.10    --  -57.83 -30.00  30.00   90
 42  \w   -130.00 -85.00   0.50    0.10    --  -77.27 -30.00 -30.00   90
 43  \w   -130.00 -85.00   0.50    0.10    --  -77.27 -30.00  90.00   90
 44  \w   -130.00 -85.00   0.50    0.10    --  -77.27 -30.00 120.00   90
 45  \w   -130.00 -85.00   0.50    0.10    --  -77.27 -30.00 150.00   90
 46  \w   -110.00 -65.00   0.50    0.10    --  -57.83 -30.00 120.00   90
 47  \w   -110.00 -65.00   0.50    0.10    --  -57.83 -30.00  60.00   90
 48  \w   -134.00 -89.00   0.50    0.10    --  -82.00 -30.00  60.00   90
 49  \w   -134.00 -89.00   0.50    0.10    --  -82.00 -30.00  30.00   90
 50  \w   -110.00 -65.00   0.50    0.10    --  -57.83 -30.00-150.00   90
 51  \w   -130.00 -85.00   0.50    0.10    --  -77.27 -30.00-180.00   90
;
_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      -0.0620357000
_diffrn_orient_matrix_UB_12      0.0261818000
_diffrn_orient_matrix_UB_13      0.1023310000
_diffrn_orient_matrix_UB_21      -0.1062352000
_diffrn_orient_matrix_UB_22      -0.1500995000
_diffrn_orient_matrix_UB_23      -0.0022029000
_diffrn_orient_matrix_UB_31      0.2415441000
_diffrn_orient_matrix_UB_32      -0.0592998000
_diffrn_orient_matrix_UB_33      0.0507355000
_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  0.0757
_diffrn_reflns_av_unetI/netI     0.0372
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.967
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            14295
_diffrn_reflns_point_group_measured_fraction_full 0.977
_diffrn_reflns_point_group_measured_fraction_max 0.922
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.542
_diffrn_reflns_theta_min         3.276
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.689
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.86543
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.41.122a (Rigaku Oxford Diffraction, 2021)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'metallic light colourless'
_exptl_crystal_colour_lustre     metallic
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.250
_exptl_crystal_description       block
_exptl_crystal_F_000             300
_exptl_crystal_size_max          0.1
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.217
_refine_diff_density_min         -0.166
_refine_diff_density_rms         0.039
_refine_ls_abs_structure_details
;
 Flack x determined using 1126 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.11(17)
_refine_ls_extinction_coef       0.007(2)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2019/2 (Sheldrick 2019)'
_refine_ls_goodness_of_fit_ref   1.133
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     186
_refine_ls_number_reflns         2747
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.133
_refine_ls_R_factor_all          0.0383
_refine_ls_R_factor_gt           0.0371
_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^)+(0.0729P)^2^+0.0061P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1044
_refine_ls_wR_factor_ref         0.1054
_reflns_Friedel_coverage         0.792
_reflns_Friedel_fraction_full    0.952
_reflns_Friedel_fraction_max     0.872
_reflns_number_gt                2639
_reflns_number_total             2747
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ra02485d2.cif
_cod_data_source_block           0320-6chenjing_auto
_cod_original_cell_volume        736.79(6)
_cod_database_code               7250590
_shelx_shelxl_version_number     2019/3
_shelx_estimated_absorpt_t_max   0.934
_shelx_estimated_absorpt_t_min   0.934
_reflns_odcompleteness_completeness 100.00
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_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:
 C4(H4), C3(H3)
2.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C1(H1A,H1B), C5(H5A,H5B)
2.c Aromatic/amide H refined with riding coordinates:
 C11(H11), C8(H8), C12(H12), C9(H9), C10(H10)
2.d Idealised Me refined as rotating group:
 C16(H16A,H16B,H16C), C18(H18A,H18B,H18C), C17(H17A,H17B,H17C)
2.e Idealised tetrahedral OH refined as rotating group:
 O20(H20)
;
_shelx_res_checksum              58745
_shelx_hkl_checksum              69111
_olex2_submission_original_sample_id 0320-6
_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 2.067
_oxdiff_exptl_absorpt_empirical_full_min 0.603