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_4118785
_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            'C15 H21 N3 O6'
_chemical_formula_weight         339.35
_space_group_IT_number           4
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 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                 95.204(6)
_cell_angle_gamma                90.00
_cell_formula_units_Z            2
_cell_length_a                   6.602(3)
_cell_length_b                   10.144(5)
_cell_length_c                   12.973(7)
_cell_measurement_reflns_used    2397
_cell_measurement_temperature    296(2)
_cell_measurement_theta_max      27.37
_cell_measurement_theta_min      2.55
_cell_volume                     865.2(7)
_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 0.998
_diffrn_measured_fraction_theta_max 0.998
_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  0.0620
_diffrn_reflns_av_sigmaI/netI    0.0838
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            7837
_diffrn_reflns_theta_full        25.00
_diffrn_reflns_theta_max         25.00
_diffrn_reflns_theta_min         2.55
_exptl_absorpt_coefficient_mu    0.102
_exptl_absorpt_correction_T_max  0.9939
_exptl_absorpt_correction_T_min  0.9829
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS (Sheldrick, 1999)'
_exptl_crystal_colour            Colourless
_exptl_crystal_density_diffrn    1.303
_exptl_crystal_description       Plate-like
_exptl_crystal_F_000             360
_exptl_crystal_size_max          0.17
_exptl_crystal_size_mid          0.11
_exptl_crystal_size_min          0.06
_refine_diff_density_max         0.385
_refine_diff_density_min         -0.275
_refine_diff_density_rms         0.090
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0(2)
_refine_ls_extinction_coef       0.183(19)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     SHELXL
_refine_ls_goodness_of_fit_ref   1.033
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     223
_refine_ls_number_reflns         3018
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.033
_refine_ls_R_factor_all          0.1146
_refine_ls_R_factor_gt           0.0743
_refine_ls_shift/su_max          0.036
_refine_ls_shift/su_mean         0.005
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.1200P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1753
_refine_ls_wR_factor_ref         0.2012
_reflns_number_gt                2076
_reflns_number_total             3018
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            ja308429f_si_005.cif
_cod_data_source_block           sotos2_0m
_cod_original_cell_volume        865.1(8)
_cod_database_code               4118785