Design and Synthesis of 1,2-Deoxy-pyranose Derivatives of Spliceostatin A toward Prostate Cancer Treatment
Yoshikawa, Yusuke; Ishibashi, Airi; Takehara, Tsunayoshi; Suzuki, Takeyuki; Murai, Kenichi; Kaneda, Yasufumi; Nimura, Keisuke; Arisawa, Mitsuhiro; ACS Medicinal Chemistry Letters  (2020) –; doi:10.1021/acsmedchemlett.0c00153

data_4517653
_publ_section_title
;
 Design and Synthesis of 1,2-Deoxy-pyranose Derivatives of Spliceostatin A
 toward Prostate Cancer Treatment
;
_journal_name_full               'ACS Medicinal Chemistry Letters'
_journal_paper_doi               10.1021/acsmedchemlett.0c00153
_journal_year                    2020
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C14 H28 O4 Si'
_chemical_formula_sum            'C14 H28 O4 Si'
_chemical_formula_weight         288.45
_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
_atom_sites_solution_primary     dual
_audit_creation_date             2019-10-30
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            12
_cell_length_a                   7.45990(10)
_cell_length_b                   21.2716(2)
_cell_length_c                   31.6447(3)
_cell_measurement_reflns_used    15195
_cell_measurement_temperature    90.15
_cell_measurement_theta_max      75.6010
_cell_measurement_theta_min      2.7890
_cell_volume                     5021.51(10)
_computing_cell_refinement       'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      90.15
_diffrn_detector                 'Rigaku HyPix-6000 area detector'
_diffrn_detector_area_resol_mean 10.0
_diffrn_detector_type            'HPC area detector'
_diffrn_measured_fraction_theta_full 0.993
_diffrn_measured_fraction_theta_max 0.966
_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    -40.00 -15.00   0.50    0.94    --  -35.00  78.00  24.00   50
  2  \w     -5.00  21.00   0.50    0.94    --   43.60 -57.00  25.00   52
  3  \w     -4.00  21.00   0.50    0.94    --   43.60 -78.00-100.00   50
  4  \w     91.00 117.00   0.50    0.94    --   43.60  78.00  24.00   52
  5  \w     47.00  72.00   0.50    0.94    --   43.60  57.00 167.00   50
  6  \w     81.00 107.00   0.50    3.77    --  109.30  78.00  24.00   52
  7  \w    113.00 138.00   0.50    3.77    --  109.30  57.00 167.00   50
  8  \w     60.00  87.00   0.50    3.77    --  109.30 -78.00-100.00   54
  9  \w    114.00 139.00   0.50    3.77    --  109.30  78.00  24.00   50
 10  \w     57.00  82.00   0.50    3.77    --  109.30 -57.00  25.00   50
 11  \w    -48.00  -5.00   0.50    0.94    --  -35.00 -77.00   0.00   86
 12  \w    -24.00   1.00   0.50    0.94    --  -35.00 -82.00   0.00   50
 13  \w    -18.00   7.00   0.50    0.94    --  -35.00  57.00 167.00   50
 14  \w      4.00  48.00   0.50    0.94    --   43.60  77.00-180.00   88
 15  \w     80.00 132.00   0.50    0.94    --   43.60  77.00 -30.00  104
 16  \w     16.00  48.00   0.50    0.94    --   43.60  77.00 -90.00   64
 17  \w    116.00 162.00   0.50    3.77    --  109.30  77.00-150.00   92
 18  \w     77.00 109.00   0.50    3.77    --  109.30  77.00-150.00   64
 19  \w     85.00 198.00   0.50    3.77    --  109.30  82.00   0.00  226
 20  \w     98.00 123.00   0.50    3.77    --  109.30 -30.00 120.00   50
 21  \w     25.00  60.00   0.50    3.77    --  109.30 -30.00 120.00   70
 22  \w    168.00 198.00   0.50    3.77    --  109.30  77.00-150.00   60
 23  \w     85.00 198.00   0.50    3.77    --  109.30  82.00 -60.00  226
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Rigaku XtaLAB PRO'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0143028000
_diffrn_orient_matrix_UB_12      -0.0484080000
_diffrn_orient_matrix_UB_13      0.0360341000
_diffrn_orient_matrix_UB_21      0.1387721000
_diffrn_orient_matrix_UB_22      0.0374950000
_diffrn_orient_matrix_UB_23      0.0258109000
_diffrn_orient_matrix_UB_31      -0.1522808000
_diffrn_orient_matrix_UB_32      0.0386951000
_diffrn_orient_matrix_UB_33      0.0201133000
_diffrn_radiation_monochromator  'multi-layer mirror optics'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0328
_diffrn_reflns_av_unetI/netI     0.0388
_diffrn_reflns_Laue_measured_fraction_full 0.993
_diffrn_reflns_Laue_measured_fraction_max 0.966
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       26
_diffrn_reflns_limit_k_min       -25
_diffrn_reflns_limit_l_max       38
_diffrn_reflns_limit_l_min       -39
_diffrn_reflns_number            25890
_diffrn_reflns_point_group_measured_fraction_full 0.969
_diffrn_reflns_point_group_measured_fraction_max 0.928
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.776
_diffrn_reflns_theta_min         2.793
_diffrn_source                   'rotating anode X-ray generator'
_diffrn_source_type              micromax007
_exptl_absorpt_coefficient_mu    1.305
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.867
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.35a (Rigaku Oxford Diffraction, 2018)
Numerical absorption correction based on gaussian integration over
			a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.145
_exptl_crystal_description       needle
_exptl_crystal_F_000             1896
_exptl_crystal_size_max          0.181
_exptl_crystal_size_mid          0.025
_exptl_crystal_size_min          0.025
_refine_diff_density_max         0.952
_refine_diff_density_min         -0.468
_refine_diff_density_rms         0.039
_refine_ls_abs_structure_details
;
 Flack x determined using 3651 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.014(8)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.047
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     535
_refine_ls_number_reflns         9706
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.047
_refine_ls_R_factor_all          0.0369
_refine_ls_R_factor_gt           0.0346
_refine_ls_shift/su_max          0.002
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0408P)^2^+1.2399P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0865
_refine_ls_wR_factor_ref         0.0876
_reflns_Friedel_coverage         0.711
_reflns_Friedel_fraction_full    0.938
_reflns_Friedel_fraction_max     0.879
_reflns_number_gt                9189
_reflns_number_total             9706
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ml0c00153_si_002.cif
_cod_data_source_block           me-epoxy-up3-1
_cod_database_code               4517653
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C14 H28 O4 Si1'
_chemical_oxdiff_usercomment     '-183C(flash cooling)'
_reflns_odcompleteness_completeness 99.27
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     68.13
_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:
 C5(H5), C43(H43), C24(H24), C44(H44), C25(H25), C10(H10), C6(H6), C29(H29),
 C48(H48)
2.b Secondary CH2 refined with riding coordinates:
 C7(H7A,H7B), C26(H26A,H26B), C45(H45A,H45B), C3(H3A,H3B), C41(H41A,H41B),
 C40(H40A,H40B), C2(H2A,H2B), C22(H22A,H22B), C21(H21A,H21B)
2.c Idealised Me refined as rotating group:
 C33(H33A,H33B,H33C), C15(H15A,H15B,H15C), C34(H34A,H34B,H34C), C14(H14A,H14B,
 H14C), C49(H49A,H49B,H49C), C38(H38A,H38B,H38C), C11(H11A,H11B,H11C), C37(H37A,
 H37B,H37C), C17(H17A,H17B,H17C), C19(H19A,H19B,H19C), C30(H30A,H30B,H30C),
 C18(H18A,H18B,H18C), C56(H56A,H56B,H56C), C55(H55A,H55B,H55C), C36(H36A,H36B,
 H36C), C52(H52A,H52B,H52C), C53(H53A,H53B,H53C), C57(H57A,H57B,H57C)
2.d Idealised tetrahedral OH refined as rotating group:
 O46(H46), O8(H8), O27(H27)
;
_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 1.363
_oxdiff_exptl_absorpt_empirical_full_min 0.745