Morpholino-based phosphorothioate analogs <i>via</i> oxathiaphospholane chemistry: synthesis, structural insights and stability.
Jastrzębska, Katarzyna; Szymańska, Agata; Pawlak, Tomasz; Dolot, Rafał; Organic & biomolecular chemistry 23 (2025) 8755–8763; doi:10.1039/d5ob01223f

data_7160729
_publ_section_title
;
 Morpholino-based phosphorothioate analogs <i>via</i> oxathiaphospholane
 chemistry: synthesis, structural insights and stability.
;
_journal_issue                   38
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              8755
_journal_page_last               8763
_journal_paper_doi               10.1039/d5ob01223f
_journal_volume                  23
_journal_year                    2025
_chemical_absolute_configuration ad
_chemical_formula_moiety
'C11 H17 N4 O5 P S2, 0.35(C1 H1 Cl3), 0.35(C2 H3 N1)'
_chemical_formula_sum            'C12.05 H18.4 Cl1.05 N4.35 O5 P S2'
_chemical_formula_weight         436.52
_chemical_name_common            OTP-N-mU-1
_chemical_name_systematic        OTP-N-mU-1
_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   mixed
_audit_creation_date             2025-07-08
_audit_creation_method
;
Olex2 1.5
(compiled 2025.05.31 svn.r86d253d1 for OlexSys, GUI svn.r7254)
;
_audit_update_record
;
2025-07-08 deposited with the CCDC.	2025-08-28 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 112.621(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   17.0836(3)
_cell_length_b                   7.22770(10)
_cell_length_c                   17.8604(3)
_cell_measurement_reflns_used    26147
_cell_measurement_temperature    99.99(10)
_cell_measurement_theta_max      79.0550
_cell_measurement_theta_min      2.6770
_cell_volume                     2035.66(6)
_computing_cell_refinement       'CrysAlisPro 1.171.43.122a (Rigaku OD, 2024)'
_computing_data_collection
'CrysAlisPro system (CCD 43.122a 64-bit (release 15-05-2024))'
_computing_data_reduction        'CrysAlisPro 1.171.43.122a (Rigaku OD, 2024)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      99.99(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 1.000
_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    -63.00  25.00   0.50    0.22    --  -47.34  59.00 138.00  176
  2  \w   -119.00 -32.00   0.50    0.22    --  -47.34 -59.00  -0.00  174
  3  \w     32.00 119.00   0.50    0.22    --   47.34  59.00 138.00  174
  4  \w    -24.00  63.00   0.50    0.22    --   47.34 -59.00  -0.00  174
  5  \w    -68.00 -19.00   0.50    0.87    --  -91.75  59.00 138.00   98
  6  \w   -163.00 -76.00   0.50    0.87    --  -91.75 -59.00  -0.00  174
  7  \w     98.00 178.00   0.50    0.87    --  113.25  59.00 138.00  160
  8  \w     42.00  68.00   0.50    0.87    --  113.25 -59.00  -0.00   52
  9  \w    -26.00  28.00   0.50    0.22    --  -47.34  19.00 -60.00  108
 10  \w     34.00  93.00   0.50    0.22    --   47.34-125.00-180.00  118
 11  \w     33.00 119.00   0.50    0.22    --   47.34  57.00-120.00  172
 12  \w   -163.00 -75.00   0.50    0.87    --  -91.75 -61.00-120.00  176
 13  \w   -163.00 -79.00   0.50    0.87    --  -91.75 -45.00 -60.00  168
 14  \w   -163.00 -69.00   0.50    0.87    --  -91.75 -77.00-150.00  188
 15  \w   -163.00 -69.00   0.50    0.87    --  -91.75 -77.00-120.00  188
 16  \w   -166.00 -78.00   0.50    0.87    --  -91.75 -15.00-120.00  176
 17  \w   -163.00 -69.00   0.50    0.87    --  -91.75 -77.00 -90.00  188
 18  \w   -163.00 -69.00   0.50    0.87    --  -91.75 -77.00-120.00  188
 19  \w    -51.00 -20.00   0.50    0.87    --  -91.75  45.00 -90.00   62
 20  \w    -51.00 -20.00   0.50    0.87    --  -91.75  45.00 -60.00   62
 21  \w   -163.00 -69.00   0.50    0.87    --  -91.75 -77.00 -90.00  188
 22  \w    -71.00 -19.00   0.50    0.87    --  -91.75  61.00  60.00  104
 23  \w   -163.00 -79.00   0.50    0.87    --  -91.75 -45.00 -60.00  168
 24  \w     96.00 156.00   0.50    0.87    --  113.25 125.00 150.00  120
 25  \w    101.00 148.00   0.50    0.87    --  113.25  45.00-120.00   94
 26  \w     43.00 104.00   0.50    0.87    --  113.25 -95.00 120.00  122
 27  \w     42.00  67.00   0.50    0.87    --  113.25 -61.00-150.00   50
 28  \w    146.00 172.00   0.50    0.87    --  113.25  61.00 -90.00   52
 29  \w     43.00  70.00   0.50    0.87    --  113.25 -61.00  30.00   54
 30  \w     98.00 141.00   0.50    0.87    --  113.25  61.00 -90.00   86
 31  \w    101.00 177.00   0.50    0.87    --  113.25  45.00-150.00  152
 32  \w     96.00 176.00   0.50    0.87    --  113.25  77.00  30.00  160
 33  \w     96.00 177.00   0.50    0.87    --  113.25 125.00-150.00  162
 34  \w    126.00 176.00   0.50    0.87    --  113.25 125.00  60.00  100
 35  \w    153.00 178.00   0.50    0.87    --  113.25  77.00  60.00   50
 36  \w     42.00  70.00   0.50    0.87    --  113.25 -61.00 120.00   56
 37  \w    144.00 170.00   0.50    0.87    --  113.25  77.00 -60.00   52
 38  \w    102.00 146.00   0.50    0.87    --  113.25  77.00 -90.00   88
 39  \w    114.00 141.00   0.50    0.87    --  113.25  77.00 -60.00   54
 40  \w    114.00 139.00   0.50    0.87    --  113.25  77.00  60.00   50
 41  \w    110.00 159.00   0.50    0.87    --  113.25  45.00-180.00   98
 42  \w     45.00  71.00   0.50    0.87    --  113.25 -61.00 -60.00   52
 43  \w     43.00  89.00   0.50    0.87    --  113.25 -95.00-180.00   92
 44  \w    101.00 154.00   0.50    0.87    --  113.25  15.00  60.00  106
 45  \w     45.00 110.00   0.50    0.87    --  113.25-125.00 120.00  130
 46  \w     42.00 105.00   0.50    0.87    --  113.25 -95.00 -30.00  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      -0.0632338000
_diffrn_orient_matrix_UB_12      0.0537136000
_diffrn_orient_matrix_UB_13      -0.0853622000
_diffrn_orient_matrix_UB_21      0.0646301000
_diffrn_orient_matrix_UB_22      0.1395149000
_diffrn_orient_matrix_UB_23      -0.0076956000
_diffrn_orient_matrix_UB_31      0.0371394000
_diffrn_orient_matrix_UB_32      -0.1519106000
_diffrn_orient_matrix_UB_33      -0.0371858000
_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  0.0507
_diffrn_reflns_av_unetI/netI     0.0349
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.976
_diffrn_reflns_limit_h_max       21
_diffrn_reflns_limit_h_min       -21
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       22
_diffrn_reflns_limit_l_min       -22
_diffrn_reflns_number            38701
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.955
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         80.318
_diffrn_reflns_theta_min         2.680
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    4.665
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.33365
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.43.122a (Rigaku Oxford Diffraction, 2024)
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    1.424
_exptl_crystal_description       block
_exptl_crystal_F_000             904
_exptl_crystal_recrystallization_method
're-crystallized from chloroform : acetonitrile : hexane 7:2:1 (v/v/v) mixture,'
_exptl_crystal_size_max          0.25
_exptl_crystal_size_mid          0.15
_exptl_crystal_size_min          0.05
_refine_diff_density_max         1.619
_refine_diff_density_min         -0.528
_refine_diff_density_rms         0.098
_refine_ls_abs_structure_details
;
 Flack x determined using 3343 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.017(9)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.047
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     485
_refine_ls_number_reflns         8524
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.047
_refine_ls_R_factor_all          0.0604
_refine_ls_R_factor_gt           0.0564
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1131P)^2^+1.4527P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1585
_refine_ls_wR_factor_ref         0.1637
_reflns_Friedel_coverage         0.810
_reflns_Friedel_fraction_full    0.997
_reflns_Friedel_fraction_max     0.930
_reflns_number_gt                7961
_reflns_number_total             8524
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ob01223f2.cif
_cod_data_source_block           kj_mun_fast_02_autored
_cod_depositor_comments          'Adding full bibliography for 7160729.cif.'
_cod_original_sg_symbol_H-M      'P 21'
_cod_original_formula_sum        'C12.05 H18.40 Cl1.05 N4.35 O5 P S2'
_cod_database_code               7160729
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H N O S P'
_shelx_estimated_absorpt_t_max   0.800
_shelx_estimated_absorpt_t_min   0.388
_diffrn_oxdiff_digest_hkl
;
43b7782016fc1886edf1a9c0ecbd4a036314df
;
_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, All O(H) groups
2. Others
 Fixed Sof: Cl02(0.7) Cl01(0.7) Cl03(0.7) C1(0.7) H1(0.7) C02(0.7) N03(0.7)
 C01(0.7) H01A(0.7) H01B(0.7) H01C(0.7)
3.a Ternary CH refined with riding coordinates:
 C106(H106), C102(H102), C206(H206), C202(H202), C1(H1)
3.b Secondary CH2 refined with riding coordinates:
 C105(H10B,H10C), C113(H11A,H11B), C103(H10D,H10E), C205(H20A,H20B), C213(H21A,
 H21B), C114(H11C,H11D), C203(H20C,H20D), C115(H11E,H11F), C214(H21C,H21D),
 C215(H21E,H21F)
3.c Aromatic/amide H refined with riding coordinates:
 N38(H38), N109(H109), N209(H209), C112(H112), C111(H111), C212(H212),
 C211(H211)
3.d Idealised Me refined as rotating group:
 C01(H01A,H01B,H01C)
3.e Idealised tetrahedral OH refined as rotating group:
 O105(H105), O205(H205)
;
_shelx_res_checksum              72946
_olex2_exptl_crystal_mounting_method
'mounted on a nylon cryo-loop with mineral oil as a cryoprotectant'
_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
- Detector area scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 3.200
_oxdiff_exptl_absorpt_empirical_full_min 0.638