Synthesis and Biological Evaluation of Epidithio-, Epitetrathio-, and bis-(Methylthio)diketopiperazines: Synthetic Methodology, Enantioselective Total Synthesis of Epicoccin G, 8,8'-epi-ent-Rostratin B, Gliotoxin, Gliotoxin G, Emethallicin E, and Haematocin and Discovery of New Antiviral and Antimalarial Agents
K. C. Nicolaou; Min Lu; Sotirios Totokotsopoulos; Philipp Heretsch; Denis Giguère; Ya-Ping Sun; David Sarlah; Thu H. Nguyen; Ian C. Wolf; Donald F. Smee; Craig W. Day; Selina Bopp; Elizabeth A. Winzeler; Journal of the American Chemical Society 134 (2012) 17320–17332; doi:10.1021/ja308429f

data_4118784
_publ_section_title
;
 Synthesis and Biological Evaluation of Epidithio-, Epitetrathio-, and
 bis-(Methylthio)diketopiperazines: Synthetic Methodology,
 Enantioselective Total Synthesis of Epicoccin G, 8,8'-epi-ent-Rostratin
 B, Gliotoxin, Gliotoxin G, Emethallicin E, and Haematocin and Discovery
 of New Antiviral and Antimalarial Agents
;
_journal_name_full               'Journal of the American Chemical Society'
_journal_page_first              17320
_journal_page_last               17332
_journal_paper_doi               10.1021/ja308429f
_journal_volume                  134
_journal_year                    2012
_chemical_formula_sum            'C18 H18 N2 O4'
_chemical_formula_weight         326.34
_space_group_IT_number           5
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_Hall  'C 2y'
_symmetry_space_group_name_H-M   'C 1 2 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_cell_angle_alpha                90.00
_cell_angle_beta                 102.8440(10)
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   23.0261(18)
_cell_length_b                   7.0220(6)
_cell_length_c                   10.1269(8)
_cell_measurement_reflns_used    2657
_cell_measurement_temperature    296(2)
_cell_measurement_theta_max      21.26
_cell_measurement_theta_min      2.43
_cell_volume                     1596.4(2)
_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-97 (Sheldrick, 2008)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 2008)'
_diffrn_ambient_temperature      296(2)
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device_type  'Bruker APEX-I CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0250
_diffrn_reflns_av_sigmaI/netI    0.0278
_diffrn_reflns_limit_h_max       26
_diffrn_reflns_limit_h_min       -26
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -8
_diffrn_reflns_limit_l_max       11
_diffrn_reflns_limit_l_min       -11
_diffrn_reflns_number            7651
_diffrn_reflns_theta_full        24.77
_diffrn_reflns_theta_max         24.77
_diffrn_reflns_theta_min         1.81
_exptl_absorpt_coefficient_mu    0.097
_exptl_absorpt_correction_T_max  0.9894
_exptl_absorpt_correction_T_min  0.9780
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS (Sheldrick, 1999)'
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.358
_exptl_crystal_description       Parallalepiped
_exptl_crystal_F_000             688
_exptl_crystal_size_max          0.23
_exptl_crystal_size_mid          0.17
_exptl_crystal_size_min          0.11
_refine_diff_density_max         0.127
_refine_diff_density_min         -0.114
_refine_diff_density_rms         0.027
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -1.6(14)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.070
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     219
_refine_ls_number_reflns         2743
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.070
_refine_ls_R_factor_all          0.0459
_refine_ls_R_factor_gt           0.0384
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0500P)^2^+0.3000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0943
_refine_ls_wR_factor_ref         0.1019
_reflns_number_gt                2426
_reflns_number_total             2743
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            ja308429f_si_004.cif
_cod_data_source_block           grst_0m
_cod_database_code               4118784