Design, Synthesis, and Biological Investigation of Epothilone B Analogues Featuring Lactone, Lactam, and Carbocyclic Macrocycles, Epoxide, Aziridine, and 1,1-Difluorocyclopropane and Other Fluorine Residues
Nicolaou, K. C.; Shelke, Yogesh G.; Dherange, Balu D.; Kempema, Aaron; Lin, Baiwei; Gu, Christine; Sandoval, Joseph; Hammond, Mikhail; Aujay, Monette; Gavrilyuk, Julia; The Journal of Organic Chemistry  (2020) –; doi:10.1021/acs.joc.0c00123

data_4037938
_publ_section_title
;
 Design, Synthesis, and Biological Investigation of Epothilone B Analogues
 Featuring Lactone, Lactam, and Carbocyclic Macrocycles, Epoxide,
 Aziridine, and 1,1-Difluorocyclopropane and Other Fluorine Residues
;
_journal_name_full               'The Journal of Organic Chemistry'
_journal_paper_doi               10.1021/acs.joc.0c00123
_journal_year                    2020
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C28 H38 F5 N O5 S, H2 O'
_chemical_formula_sum            'C28 H40 F5 N O6 S'
_chemical_formula_weight         613.67
_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   mixed
_atom_sites_solution_primary     direct
_audit_creation_date             2019-10-04
_audit_creation_method
;
Olex2 1.2-beta
(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            4
_cell_length_a                   5.8864(2)
_cell_length_b                   17.5780(4)
_cell_length_c                   29.0647(7)
_cell_measurement_reflns_used    9904
_cell_measurement_temperature    100
_cell_measurement_theta_max      68.215
_cell_measurement_theta_min      2.94
_cell_volume                     3007.36(14)
_computing_cell_refinement       'SAINT v8.38A (Bruker, 2017)'
_computing_data_collection       'APEX3 v2017.3-0 (Bruker, 2017)'
_computing_data_reduction        'SAINT v8.38A (Bruker, 2017)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL (Sheldrick, 2008)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      100.0
_diffrn_detector                 'Bruker APEX-II CCD'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            'CCD Area Detector'
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.997
_diffrn_measurement_device       'Kappa Four-Circle Diffractometer'
_diffrn_measurement_device_type  'Bruker X8 APEX II'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  'Double Bounce Multilayer Mirrors'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0266
_diffrn_reflns_av_unetI/netI     0.0224
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.997
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       19
_diffrn_reflns_limit_k_min       -21
_diffrn_reflns_limit_l_max       34
_diffrn_reflns_limit_l_min       -33
_diffrn_reflns_number            23899
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.995
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         68.362
_diffrn_reflns_theta_min         2.938
_diffrn_source                   'Micro Focus Rotating Anode'
_diffrn_source_type              'Bruker Microstar FR-592'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    1.596
_exptl_absorpt_correction_T_max  0.5849
_exptl_absorpt_correction_T_min  0.5012
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.0809 before and 0.0373 after correction. The Ratio of minimum to maximum transmission is 0.8569. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.355
_exptl_crystal_description       needle
_exptl_crystal_F_000             1296
_exptl_crystal_size_max          0.22
_exptl_crystal_size_mid          0.09
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.222
_refine_diff_density_min         -0.152
_refine_diff_density_rms         0.036
_refine_ls_abs_structure_details
;
 Flack x determined using 2193 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.007(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.063
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     386
_refine_ls_number_reflns         5476
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.063
_refine_ls_R_factor_all          0.0277
_refine_ls_R_factor_gt           0.0267
_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^)+(0.0340P)^2^+0.8663P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0669
_refine_ls_wR_factor_ref         0.0675
_reflns_Friedel_coverage         0.726
_reflns_Friedel_fraction_full    0.997
_reflns_Friedel_fraction_max     0.993
_reflns_number_gt                5335
_reflns_number_total             5476
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo0c00123_si_003.cif
_cod_data_source_block           kcnic13_0m_a
_cod_depositor_comments
;
The following automatic conversions were performed:

data item '_diffrn_radiation_probe' value 'X-ray' was changed to
'x-ray' in accordance with the
/home/data/users/saulius/crontab/automatic-downloads/rss-feeds/ACS/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 last updated on
2011-04-26.

Automatic conversion script
Id: cif_fix_values 7556 2019-12-06 15:28:31Z antanas 
;
_cod_database_code               4037938
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_max   0.924
_shelx_estimated_absorpt_t_min   0.720
_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:
 C8(H8), C10(H10), C25(H25), C16(H16), C18(H18), C19(H19)
2.b Secondary CH2 refined with riding coordinates:
 C13(H13A,H13B), C9(H9A,H9B), C26(H26A,H26B), C14(H14A,H14B), C15(H15A,H15B)
2.c Aromatic/amide H refined with riding coordinates:
 C5(H5), C3(H3)
2.d Idealised Me refined as rotating group:
 C23(H23A,H23B,H23C), C20(H20A,H20B,H20C), C7(H7A,H7B,H7C), C28(H28A,H28B,
 H28C), C24(H24A,H24B,H24C), C17(H17A,H17B,H17C)
2.e Idealised tetrahedral OH refined as rotating group:
 O2(H2), O6(H6)
;
_shelx_res_checksum              43801
_shelx_hkl_checksum              76752
_olex2_submission_special_instructions 'No special instructions were received'