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_7250591
_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        1
_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.cc2mnr13
_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
;
2025-03-21 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                   5.5276(2)
_cell_length_b                   22.2991(8)
_cell_length_c                   12.7260(4)
_cell_measurement_reflns_used    10473
_cell_measurement_temperature    103(2)
_cell_measurement_theta_max      73.9460
_cell_measurement_theta_min      3.8710
_cell_volume                     1568.61(9)
_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      103(2)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            'HyPix-Arc 150'
_diffrn_measured_fraction_theta_full 0.9964
_diffrn_measured_fraction_theta_max 0.9727
_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    -92.00 -31.00   0.50    0.05    --  -77.31 111.00 120.00  122
  2  \w    -92.00 -67.00   0.50    0.05    --  -77.31 111.00  90.00   50
  3  \w    -92.00 -31.00   0.50    0.05    --  -77.31 111.00 -60.00  122
  4  \w    -80.00 -24.00   0.50    0.05    --  -68.04 100.00-153.00  112
  5  \w    -89.00 -33.00   0.50    0.05    --  -77.31 100.00-153.00  112
  6  \w    -69.00 -13.00   0.50    0.05    --  -57.13 100.00-153.00  112
  7  \w   -109.00 -38.00   0.50    0.05    --  -57.13 -15.00-120.00  142
  8  \w   -130.00 -85.00   0.50    0.05    --  -77.31 -30.00-180.00   90
  9  \w   -130.00 -85.00   0.50    0.05    --  -77.31 -30.00-120.00   90
 10  \w   -130.00 -85.00   0.50    0.05    --  -77.31 -30.00  60.00   90
 11  \w     85.00 131.00   0.50    0.05    --   78.29  30.00 150.00   92
 12  \w     92.00 138.00   0.50    0.05    --   85.54  30.00 120.00   92
 13  \w     60.00 106.00   0.50    0.05    --   53.69  30.00 120.00   92
 14  \w     71.00 117.00   0.50    0.05    --   64.60  30.00  60.00   92
 15  \w     92.00 138.00   0.50    0.05    --   85.54  30.00   0.00   92
 16  \w     85.00 131.00   0.50    0.05    --   78.29  30.00  30.00   92
 17  \w     85.00 131.00   0.50    0.05    --   78.29  30.00 -30.00   92
 18  \w     85.00 131.00   0.50    0.05    --   78.29  30.00 -60.00   92
 19  \w     71.00 117.00   0.50    0.05    --   64.60  30.00 -90.00   92
 20  \w     92.00 138.00   0.50    0.05    --   85.54  30.00-150.00   92
 21  \w     92.00 138.00   0.50    0.05    --   85.54  30.00-180.00   92
 22  \w     92.00 138.00   0.50    0.05    --   85.54  30.00  90.00   92
 23  \w      9.00  65.00   0.50    0.05    --   53.69-100.00 101.00  112
 24  \w     20.00  76.00   0.50    0.05    --   64.60-100.00 101.00  112
 25  \w     34.00  90.00   0.50    0.05    --   78.29-100.00 101.00  112
 26  \w     41.00  92.00   0.50    0.05    --   85.54-100.00 101.00  102
 27  \w     35.00  86.00   0.50    0.05    --   78.29 -95.00  30.00  102
 28  \w     42.00  92.00   0.50    0.05    --   85.54 -95.00   0.00  100
 29  \w     21.00  73.00   0.50    0.05    --   64.60 -95.00 -30.00  104
 30  \w     35.00  86.00   0.50    0.05    --   78.29 -95.00 -90.00  102
 31  \w     42.00  92.00   0.50    0.05    --   85.54 -95.00-180.00  100
;
_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      -0.2386456000
_diffrn_orient_matrix_UB_12      -0.0354438000
_diffrn_orient_matrix_UB_13      0.0069801000
_diffrn_orient_matrix_UB_21      0.1148854000
_diffrn_orient_matrix_UB_22      -0.0421692000
_diffrn_orient_matrix_UB_23      0.0818901000
_diffrn_orient_matrix_UB_31      -0.0867064000
_diffrn_orient_matrix_UB_32      0.0416970000
_diffrn_orient_matrix_UB_33      0.0888847000
_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  0.0744
_diffrn_reflns_av_unetI/netI     0.0412
_diffrn_reflns_Laue_measured_fraction_full 0.9964
_diffrn_reflns_Laue_measured_fraction_max 0.9727
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       26
_diffrn_reflns_limit_k_min       -26
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            16020
_diffrn_reflns_point_group_measured_fraction_full 0.9772
_diffrn_reflns_point_group_measured_fraction_max 0.9356
_diffrn_reflns_theta_full        67.6840
_diffrn_reflns_theta_max         74.23
_diffrn_reflns_theta_min         3.96
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.774
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.57909
_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    1.251
_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         0.4476
_refine_diff_density_min         -0.4465
_refine_diff_density_rms         0.0955
_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   0.14(9)
_refine_ls_d_res_high            0.8011
_refine_ls_d_res_low             11.1496
_refine_ls_goodness_of_fit_ref   1.0474
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_constraints    35
_refine_ls_number_parameters     194
_refine_ls_number_reflns         2978
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.0474
_refine_ls_R_factor_all          0.0758
_refine_ls_R_factor_gt           0.0655
_refine_ls_shift/su_max          0.0008
_refine_ls_shift/su_mean         0.0002
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1P)^2^+1.1509P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1707
_refine_ls_wR_factor_ref         0.1783
_reflns_Friedel_coverage         0.883
_reflns_limit_h_max              6
_reflns_limit_h_min              -6
_reflns_limit_k_max              26
_reflns_limit_k_min              -26
_reflns_limit_l_max              15
_reflns_limit_l_min              -15
_reflns_number_gt                2593
_reflns_number_total             2978
_reflns_threshold_expression     I>=2u(I)
_cod_data_source_file            d5ra02485d2.cif
_cod_data_source_block           15shang
_cod_original_sg_symbol_Hall     ' P 2ac 2ab'
_cod_database_code               7250591
_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:
 C007(H007), C008(H008)
2.b Secondary CH2 refined with riding coordinates:
 C00B(H00b,H00c), C00E(H00e,H00f), C00F(H00g,H00h)
2.c Aromatic/amide H refined with riding coordinates:
 C00A(H00A), C00D(H00D), C00H(H00i), C00I(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_exptl_crystal_mounting_method loop
_olex2_submission_original_sample_id 1
_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 2.452
_oxdiff_exptl_absorpt_empirical_full_min 0.491