A synthesis of 1β-hydroxytestosterone, a metabolite of xenobiotic human cytochrome P450 enzymes, beginning with a borylation of boldione.
Elizondo, Anna I.; McCarty, Kevin D.; Arman, Hadi D.; Guengerich, F. Peter; Yoshimoto, Francis K.; Organic & biomolecular chemistry 23 (2025) 9618–9623; doi:10.1039/d5ob01218j

data_7160724
_publ_section_title
;
 A synthesis of 1&#x3b2;-hydroxytestosterone, a metabolite of xenobiotic
 human cytochrome P450 enzymes, beginning with a borylation of boldione.
;
_journal_issue                   42
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              9618
_journal_page_last               9623
_journal_paper_doi               10.1039/d5ob01218j
_journal_volume                  23
_journal_year                    2025
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C25 H37 B O4'
_chemical_formula_sum            'C25 H37 B O4'
_chemical_formula_weight         412.35
_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'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2025-05-01
_audit_creation_method
;
Olex2 1.5
(compiled 2025.03.04 svn.red2d20d0 for OlexSys, GUI svn.r7188)
;
_audit_update_record
;
2025-05-02 deposited with the CCDC.	2025-09-03 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   11.4856(2)
_cell_length_b                   15.6493(3)
_cell_length_c                   25.3082(5)
_cell_measurement_reflns_used    21149
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      76.4840
_cell_measurement_theta_min      3.3090
_cell_volume                     4548.94(15)
_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  'SHELXL 2014/7 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_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
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.976
_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     39.00  65.00   0.50    1.25    --  106.92 -77.00-150.00   52
  2  \w     67.00  93.00   0.50    1.25    --  106.92 -77.00-150.00   52
  3  \w     36.00  92.00   0.50    1.25    --  106.92 -77.00 -60.00  112
  4  \w     38.00  71.00   0.50    1.25    --  106.92 -61.00 -30.00   66
  5  \w     34.00  70.00   0.50    1.25    --  106.92 -61.00   0.00   72
  6  \w     34.00  71.00   0.50    1.25    --  106.92 -61.00  60.00   74
  7  \w     34.00  60.00   0.50    1.25    --  106.92 -61.00  90.00   52
  8  \w     42.00 101.00   0.50    1.25    --  106.92 -77.00 120.00  118
  9  \w    -25.00  53.00   0.50    0.31    --   46.89 -47.00  98.00  156
 10  \w     99.00 175.00   0.50    1.25    --  106.92  30.00   0.00  152
 11  \w     92.00 178.00   0.50    1.25    --  106.92  47.00-112.00  172
 12  \w     33.00 119.00   0.50    0.31    --   46.89  47.00-112.00  172
 13  \w    -85.00 -13.00   0.50    0.31    --  -46.89 125.00 -60.00  144
 14  \w    -84.00 -23.00   0.50    1.25    --  -91.75 125.00 -90.00  122
 15  \w    -74.00 -48.00   0.50    1.25    --  -91.75 125.00  30.00   52
 16  \w    -68.00 -19.00   0.50    1.25    --  -91.75  61.00 -60.00   98
 17  \w    -53.00 -20.00   0.50    1.25    --  -91.75  47.00-112.00   66
 18  \w    -51.00 -19.00   0.50    1.25    --  -91.75  45.00-150.00   64
 19  \w    -69.00 -43.00   0.50    1.25    --  -91.75  61.00-180.00   52
 20  \w    -49.00 -19.00   0.50    1.25    --  -91.75  45.00-180.00   60
 21  \w    -53.00  25.00   0.50    0.31    --  -46.89  47.00-112.00  156
 22  \w    -49.00 -23.00   0.50    1.25    --  -91.75  45.00   0.00   52
 23  \w    -51.00 -19.00   0.50    1.25    --  -91.75  45.00  90.00   64
 24  \w    -30.00  29.00   0.50    0.31    --  -46.89  19.00  30.00  118
 25  \w   -119.00 -31.00   0.50    0.31    --  -46.89 -47.00  98.00  176
 26  \w   -164.00 -76.00   0.50    1.25    --  -91.75 -47.00  98.00  176
 27  \w   -164.00-101.00   0.50    1.25    --  -91.75 -77.00-150.00  126
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0301516000
_diffrn_orient_matrix_UB_12      -0.0575217000
_diffrn_orient_matrix_UB_13      0.0475474000
_diffrn_orient_matrix_UB_21      -0.1302030000
_diffrn_orient_matrix_UB_22      0.0072606000
_diffrn_orient_matrix_UB_23      -0.0137354000
_diffrn_orient_matrix_UB_31      0.0099797000
_diffrn_orient_matrix_UB_32      -0.0795125000
_diffrn_orient_matrix_UB_33      -0.0355659000
_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  0.0590
_diffrn_reflns_av_unetI/netI     0.0395
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.976
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -19
_diffrn_reflns_limit_l_max       28
_diffrn_reflns_limit_l_min       -31
_diffrn_reflns_number            43186
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.976
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.725
_diffrn_reflns_theta_min         3.320
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.621
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.79886
_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 colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.204
_exptl_crystal_description       plate
_exptl_crystal_F_000             1792
_exptl_crystal_recrystallization_method 'Re-crystallisation from solvent'
_exptl_crystal_size_max          0.193
_exptl_crystal_size_mid          0.164
_exptl_crystal_size_min          0.058
_refine_diff_density_max         0.500
_refine_diff_density_min         -0.371
_refine_diff_density_rms         0.066
_refine_ls_abs_structure_details
;
 Refined as an inversion twin.
;
_refine_ls_abs_structure_Flack   0.2(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.099
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     542
_refine_ls_number_reflns         9109
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.099
_refine_ls_R_factor_all          0.0761
_refine_ls_R_factor_gt           0.0700
_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^)+(0.0100P)^2^+8.0000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1479
_refine_ls_wR_factor_ref         0.1512
_reflns_Friedel_coverage         0.803
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.976
_reflns_number_gt                8301
_reflns_number_total             9109
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ob01218j2.cif
_cod_data_source_block           hpd809c
_cod_depositor_comments
'Adding full bibliography for 7160722--7160727.cif.'
_cod_database_code               7160724
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C H O B'
_chemical_oxdiff_usercomment     AEI-075C2
_shelx_estimated_absorpt_t_max   0.965
_shelx_estimated_absorpt_t_min   0.890
_diffrn_oxdiff_digest_hkl
;
010a7e9e59604133ce185fe2d0d8a635afe14a
;
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.8(4)
 0.2(4)
2. 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 C(H,H,H,H,H,H) groups
3. Uiso/Uaniso restraints and constraints
Uanis(O7B) = Uanis(O8A) = Uanis(C46B) = Uanis(C45B) = Uanis(C45A) = Uanis(O8B)
= Uanis(C19) = Uanis(O7A) = Uanis(C46A)
4. Others
 Fixed Sof: O8B(0.8) O7A(0.8) H48A(0.8) H48B(0.8) H48C(0.8) H48D(0.2)
 H48E(0.2) H48F(0.2) H49A(0.8) H49B(0.8) H49C(0.8) H49D(0.2) H49E(0.2)
 H49F(0.2) H47A(0.8) H47B(0.8) H47C(0.8) H47D(0.2) H47E(0.2) H47F(0.2)
 H50A(0.8) H50B(0.8) H50C(0.8) H50D(0.2) H50E(0.2) H50F(0.2) C45A(0.8)
 C46A(0.8) O7B(0.2) O8A(0.2) C46B(0.2) C45B(0.2)
5.a Ternary CH refined with riding coordinates:
 C16(H16), C8(H8), C9(H9), C33(H33), C1(H1), C41(H41), C34(H34), C26(H26)
5.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C15(H15A,H15B), C7(H7A,H7B), C40(H40A,H40B), C10(H10A,H10B),
 C32(H32A,H32B), C11(H11A,H11B), C27(H27A,H27B), C14(H14A,H14B), C6(H6A,H6B),
 C31(H31A,H31B), C35(H35A,H35B), C39(H39A,H39B), C36(H36A,H36B)
5.c Aromatic/amide H refined with riding coordinates:
 C29(H29), C4(H4)
5.d Idealised Me refined as rotating group:
 C19(H19A,H19B,H19C), C22(H22A,H22B,H22C), C43(H43A,H43B,H43C), C18(H18A,H18B,
 H18C), C44(H44A,H44B,H44C), C23(H23A,H23B,H23C), C48(H48A,H48B,H48C), C48(H48D,
 H48E,H48F), C49(H49A,H49B,H49C), C49(H49D,H49E,H49F), C25(H25A,H25B,H25C),
 C24(H24A,H24B,H24C), C47(H47A,H47B,H47C), C47(H47D,H47E,H47F), C50(H50A,H50B,
 H50C), C50(H50D,H50E,H50F)
;
_shelx_res_checksum              40038
_olex2_exptl_crystal_mounting_method 'nylon loop'
_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 1.299
_oxdiff_exptl_absorpt_empirical_full_min 0.790