Intercepted Retro-Nazarov Reaction: Syntheses of Amidino-Rocaglate Derivatives and Their Biological Evaluation as eIF4A Inhibitors.
Zhang, Wenhan; Chu, Jennifer; Cyr, Andrew M.; Yueh, Han; Brown, Lauren E.; Wang, Tony T.; Pelletier, Jerry; Porco, Jr, John A; Journal of the American Chemical Society 141 (2019) 12891–12900; doi:10.1021/jacs.9b06446

data_4127766
_publ_section_title
;
 Intercepted Retro-Nazarov Reaction: Syntheses of Amidino-Rocaglate
 Derivatives and Their Biological Evaluation as eIF4A Inhibitors.
;
_journal_issue                   32
_journal_name_full               'Journal of the American Chemical Society'
_journal_page_first              12891
_journal_page_last               12900
_journal_paper_doi               10.1021/jacs.9b06446
_journal_volume                  141
_journal_year                    2019
_chemical_formula_moiety         'C35 H32 N2 O7, C H Cl3'
_chemical_formula_sum            'C36 H33 Cl3 N2 O7'
_chemical_formula_weight         711.99
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_symmetry_space_group_name_Hall  '-P 1'
_symmetry_space_group_name_H-M   'P -1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2017-10-18
_audit_creation_method
;
Olex2 1.2
(compiled 2017.08.10 svn.r3458 for OlexSys, GUI svn.r5381)
;
_audit_update_record
;
2017-10-18 # Formatted by publCIF

;
_cell_angle_alpha                67.226(4)
_cell_angle_beta                 74.054(4)
_cell_angle_gamma                88.462(4)
_cell_formula_units_Z            2
_cell_length_a                   10.4389(9)
_cell_length_b                   13.2789(12)
_cell_length_c                   13.6962(12)
_cell_measurement_reflns_used    9650
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      67.125
_cell_measurement_theta_min      3.624
_cell_volume                     1676.4(3)
_computing_cell_refinement       'SAINT (Bruker, 2006)'
_computing_data_collection       'APEX3 (Bruker, 2016)'
_computing_data_reduction        'SAINT (Bruker, 2006)'
_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      99.96
_diffrn_measured_fraction_theta_full 0.923
_diffrn_measured_fraction_theta_max 0.923
_diffrn_measurement_device_type  'Bruker X8 Proteum-R'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  Montel
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0760
_diffrn_reflns_av_unetI/netI     0.0467
_diffrn_reflns_Laue_measured_fraction_full 0.923
_diffrn_reflns_Laue_measured_fraction_max 0.923
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            40027
_diffrn_reflns_point_group_measured_fraction_full 0.923
_diffrn_reflns_point_group_measured_fraction_max 0.923
_diffrn_reflns_theta_full        67.197
_diffrn_reflns_theta_max         67.197
_diffrn_reflns_theta_min         3.653
_diffrn_source                   'rotating anode'
_exptl_absorpt_coefficient_mu    2.917
_exptl_absorpt_correction_T_max  0.7528
_exptl_absorpt_correction_T_min  0.6332
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS (Sheldrick, 2015)'
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.411
_exptl_crystal_description       prism
_exptl_crystal_F_000             740
_exptl_crystal_size_max          0.159
_exptl_crystal_size_mid          0.141
_exptl_crystal_size_min          0.062
_exptl_transmission_factor_max   0.7528
_exptl_transmission_factor_min   0.6332
_refine_diff_density_max         0.558
_refine_diff_density_min         -0.600
_refine_diff_density_rms         0.077
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.095
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     466
_refine_ls_number_reflns         5544
_refine_ls_number_restraints     66
_refine_ls_restrained_S_all      1.100
_refine_ls_R_factor_all          0.0832
_refine_ls_R_factor_gt           0.0767
_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^)+(0.0251P)^2^+7.0356P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1798
_refine_ls_wR_factor_ref         0.1831
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4872
_reflns_number_total             5544
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ja9b06446_si_002.cif
_cod_data_source_block           zhang1a_0m
_cod_database_code               4127766
_shelx_shelxl_version_number     2016/6
_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. Restrained distances
 Cl5S-C1S
 1.75 with sigma of 0.02
 Cl2S-C1S
 1.75 with sigma of 0.02
 Cl3S-C1S
 1.75 with sigma of 0.02
 Cl6S-C1S
 1.75 with sigma of 0.02
 Cl1S-C1S
 1.75 with sigma of 0.02
 Cl4S-C1S
 1.75 with sigma of 0.02
 Cl2S-C1S \\sim Cl5S-C1S
 with sigma of 0.02
 Cl3S-C1S \\sim Cl6S-C1S
 with sigma of 0.02
 Cl4S-C1S \\sim Cl1S-C1S
 with sigma of 0.02
3. Rigid bond restraints
 C28, C29, C30, C31, C32, C33, C34
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
4. Uiso/Uaniso restraints and constraints
C28 \\sim C29 \\sim C30 \\sim C31 \\sim C32 \\sim C33 \\sim C34: within 1.7A
with sigma of 0.04 and sigma for terminal atoms of 0.08
5. Others
 Sof(Cl1S)=Sof(H1SA)=Sof(Cl3S)=Sof(Cl2S)=1-FVAR(1)
 Sof(Cl5S)=Sof(H1S)=Sof(Cl4S)=Sof(Cl6S)=FVAR(1)
6.a Ternary CH refined with riding coordinates:
 C8(H8), C7(H7A), C1S(H1SA), C1S(H1S)
6.b Aromatic/amide H refined with riding coordinates:
 N1(H1), C22(H22), C18(H18), C17(H17), C25(H25), C14(H14), C3(H3), C13(H13),
 C30(H30), C2(H2), C5(H5), C1(H1A), C34(H34), C6(H6), C33(H33), C31(H31),
 C32(H32)
6.c Idealised Me refined as rotating group:
 C24(H24A,H24B,H24C), C10(H10A,H10B,H10C), C16(H16A,H16B,H16C), C27(H27A,H27B,
 H27C)
6.d Idealised tetrahedral OH refined as rotating group:
 O7(H7)
;
_shelx_res_checksum              38422
_shelx_hkl_checksum              38300
_olex2_submission_special_instructions 'No special instructions were received'
_publcif_funding_html
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