Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels-Alder Reaction and Di-t-butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer dl-Deoxypodophyllotoxin.
Saavedra, Diana I.; Rencher, Benjamin D.; Kwon, Doo-Hyun; Smith, Stacey J.; Ess, Daniel H.; Andrus, Merritt B.; The Journal of organic chemistry 83 (2018) 2018–2026; doi:10.1021/acs.joc.7b02957

data_4033464
_publ_section_title
;
 Synthesis and Computational Studies Demonstrate the Utility of an
 Intramolecular Styryl Diels-Alder Reaction and Di-t-butylhydroxytoluene
 Assisted [1,3]-Shift to Construct Anticancer dl-Deoxypodophyllotoxin.
;
_journal_issue                   4
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              2018
_journal_page_last               2026
_journal_paper_doi               10.1021/acs.joc.7b02957
_journal_volume                  83
_journal_year                    2018
_chemical_formula_sum            'C22 H20 O7'
_chemical_formula_weight         396.38
_space_group_crystal_system      monoclinic
_space_group_IT_number           9
_space_group_name_Hall           'C -2yc'
_space_group_name_H-M_alt        'C 1 c 1'
_symmetry_space_group_name_Hall  'C -2yc'
_symmetry_space_group_name_H-M   'C 1 c 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-2014/7
_cell_angle_alpha                90
_cell_angle_beta                 101.048(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   4.6806(2)
_cell_length_b                   33.3839(11)
_cell_length_c                   11.9303(4)
_cell_measurement_reflns_used    9807
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      68.27
_cell_measurement_theta_min      2.65
_cell_volume                     1829.64(12)
_computing_cell_refinement       'Bruker SAINT'
_computing_data_collection       'Bruker APEX2'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-2014/7 (Sheldrick, 2014)'
_computing_structure_solution    'SHELXS-97 (Sheldrick 2008)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0398
_diffrn_reflns_av_unetI/netI     0.0196
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       5
_diffrn_reflns_limit_h_min       -5
_diffrn_reflns_limit_k_max       40
_diffrn_reflns_limit_k_min       -40
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            32497
_diffrn_reflns_point_group_measured_fraction_full 0.967
_diffrn_reflns_point_group_measured_fraction_max 0.965
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         68.262
_diffrn_reflns_theta_min         2.647
_diffrn_source                   'Bruker-Nonius FR591 Cu rotating anode'
_exptl_absorpt_coefficient_mu    0.900
_exptl_absorpt_correction_T_max  0.7531
_exptl_absorpt_correction_T_min  0.6282
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS (Sheldrick, 2009)'
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.439
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       plate
_exptl_crystal_F_000             832
_exptl_crystal_size_max          0.440
_exptl_crystal_size_mid          0.380
_exptl_crystal_size_min          0.060
_refine_diff_density_max         0.171
_refine_diff_density_min         -0.164
_refine_diff_density_rms         0.036
_refine_ls_abs_structure_details
; 
 Flack x determined using 1527 quotients [(I+)-(I-)]/[(I+)+(I-)] 
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259). 
;
_refine_ls_abs_structure_Flack   0.07(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.830
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     288
_refine_ls_number_reflns         3245
_refine_ls_number_restraints     449
_refine_ls_restrained_S_all      0.783
_refine_ls_R_factor_all          0.0263
_refine_ls_R_factor_gt           0.0261
_refine_ls_shift/su_max          0.021
_refine_ls_shift/su_mean         0.003
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1000P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0832
_refine_ls_wR_factor_ref         0.0836
_reflns_Friedel_coverage         0.919
_reflns_Friedel_fraction_full    0.934
_reflns_Friedel_fraction_max     0.929
_reflns_number_gt                3216
_reflns_number_total             3245
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo7b02957_si_003.cif
_cod_data_source_block           16086
_cod_depositor_comments
'Adding full bibliography for 4033464--4033465.cif.'
_cod_database_code               4033464
_shelx_shelxl_version_number     2014/7
_shelx_estimated_absorpt_t_min   0.693
_shelx_estimated_absorpt_t_max   0.948
_shelx_res_checksum              39364
_shelx_hkl_checksum              31875