Synthesis, molecular editing, and biological assessment of the potent cytotoxin leiodermatolide.
Mailhol, Damien; Willwacher, Jens; Kausch-Busies, Nina; Rubitski, Elizabeth E.; Sobol, Zhanna; Schuler, Maik; Lam, My-Hanh; Musto, Sylvia; Loganzo, Frank; Maderna, Andreas; Fürstner, Alois; Journal of the American Chemical Society 136 (2014) 15719–15729; doi:10.1021/ja508846g

data_4122865
_publ_section_title
;
 Synthesis, molecular editing, and biological assessment of the potent
 cytotoxin leiodermatolide.
;
_journal_issue                   44
_journal_name_full               'Journal of the American Chemical Society'
_journal_page_first              15719
_journal_page_last               15729
_journal_paper_doi               10.1021/ja508846g
_journal_volume                  136
_journal_year                    2014
_chemical_absolute_configuration rmad
_chemical_compound_source        dichloromethane,diethylether
_chemical_formula_moiety         'C34 H51 N O8, H2 O'
_chemical_formula_sum            'C34 H53 N O9'
_chemical_formula_weight         619.77
_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'
_symmetry_cell_setting           orthorhombic
_symmetry_Int_Tables_number      19
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_block_code                MID-MB-311
_audit_creation_date             2014-06-10
_audit_creation_method
;
Olex2 1.2
(compiled 2014.05.21 svn.r2940 for OlexSys, GUI svn.r4846)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.7417(5)
_cell_length_b                   18.3901(9)
_cell_length_c                   21.5680(11)
_cell_measurement_reflns_used    9947
_cell_measurement_temperature    100
_cell_measurement_theta_max      67.5037
_cell_measurement_theta_min      3.1580
_cell_volume                     3467.3(3)
_computing_cell_refinement       'SAINT software (Bruker AXS, 2004)'
_computing_data_collection       'APEX2 (Bruker AXS, 2005-2013)'
_computing_data_reduction        'SAINT software (Bruker AXS, 2004)'
_computing_molecular_graphics    'DIAMOND (Crystal Impact GbR, 1997-2012)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL (G. M. Sheldrick, 2013)'
_computing_structure_solution    'SHELXS (G. M. Sheldrick, 2013)'
_diffrn_ambient_temperature      100
_diffrn_detector_area_resol_mean 66.67
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.995
_diffrn_measurement_device_type  'Bruker AXS X8 Proteum'
_diffrn_measurement_method       'CCD \f- and \w-scans'
_diffrn_radiation_monochromator  'MONTEL graded multilayer optic'
_diffrn_radiation_type           Cu-K\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0421
_diffrn_reflns_av_unetI/netI     0.0172
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.995
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       21
_diffrn_reflns_limit_k_min       -22
_diffrn_reflns_limit_l_max       25
_diffrn_reflns_limit_l_min       -25
_diffrn_reflns_number            82852
_diffrn_reflns_point_group_measured_fraction_full 0.995
_diffrn_reflns_point_group_measured_fraction_max 0.993
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         67.812
_diffrn_reflns_theta_min         3.158
_diffrn_source                   '0.2 x 2mm^2^ focus rotating anode'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.692
_exptl_absorpt_correction_T_max  0.94495
_exptl_absorpt_correction_T_min  0.77987
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details   'SADABS (Bruker AXS, 2012)'
_exptl_crystal_colour            colorless
_exptl_crystal_colour_primary    colorless
_exptl_crystal_density_diffrn    1.187
_exptl_crystal_description       needle
_exptl_crystal_F_000             1344
_exptl_crystal_size_max          0.64
_exptl_crystal_size_mid          0.10
_exptl_crystal_size_min          0.10
_refine_diff_density_max         0.114
_refine_diff_density_min         -0.154
_refine_diff_density_rms         0.033
_refine_ls_abs_structure_details
;
 Flack x determined using 2592 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.03(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.044
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     417
_refine_ls_number_reflns         6247
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.044
_refine_ls_R_factor_all          0.0284
_refine_ls_R_factor_gt           0.0274
_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^)+(0.0326P)^2^+0.8151P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0666
_refine_ls_wR_factor_ref         0.0673
_reflns_Friedel_coverage         0.765
_reflns_Friedel_fraction_full    0.992
_reflns_Friedel_fraction_max     0.989
_reflns_number_gt                6087
_reflns_number_total             6247
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ja508846g_si_002.cif
_cod_data_source_block           8776sadabs
_cod_depositor_comments
;
The following automatic conversions were performed:

'_symmetry_cell_setting' value 'ORTHORHOMBIC' changed to
'orthorhombic' according to
/home/saulius/struct/COD-crude-data--automatic-downloads/rss-feeds/ACS/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 from 2011-04-26.

Automatic conversion script
Id: cif_fix_values 2827 2014-09-09 07:05:25Z andrius 

 Adding full bibliography for 4122864--4122865.cif.
;
_cod_original_sg_symbol_Hall     'p 2ac 2ab'
_cod_database_code               4122865
_shelx_estimated_absorpt_t_max   0.934
_shelx_estimated_absorpt_t_min   0.651
_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, All O(H,H) groups
2.a Free rotating group:
 O9(H9D,H9E)
2.b Ternary CH refined with riding coordinates:
 C1(H1), C8(H8), C10(H10), C11(H11), C13(H13), C19(H19), C28(H28), C29(H29)
2.c Secondary CH2 refined with riding coordinates:
 C3(H3A,H3B), C4(H4A,H4B), C26(H26A,H26B), C31(H31A,H31B), C33(H33A,H33B)
2.d Aromatic/amide H refined with riding coordinates:
 C5(H5), C15(H15), C16(H16), C17(H17), C18(H18), C23(H23), C24(H24), C25(H25)
2.e Idealised Me refined as rotating group:
 C7(H7A,H7B,H7C), C9(H9A,H9B,H9C), C12(H12A,H12B,H12C), C20(H20A,H20B,H20C),
 C22(H22A,H22B,H22C), C32(H32A,H32B,H32C), C34(H34A,H34B,H34C)
2.f Idealised tetrahedral OH refined as rotating group:
 O3(H3), O6(H6)
;
_shelx_res_checksum              30876
_olex2_submission_special_instructions 'No special instructions were received'
_shelxl_version_number           2014-3