Total synthesis of a key series of vinblastines modified at C4 that define the importance and surprising trends in activity.
Yang, Shouliang; Sankar, Kuppusamy; Skepper, Colin K.; Barker, Timothy J.; Lukesh, 3rd, John C; Brody, Daniel M.; Brütsch, Manuela M; Boger, Dale L.; Chemical science 8 (2017) 1560–1569; doi:10.1039/C6SC04146A

data_1544464
_publ_section_title
;
 Total synthesis of a key series of vinblastines modified at C4 that
 define the importance and surprising trends in activity.
;
_journal_issue                   2
_journal_name_full               'Chemical science'
_journal_page_first              1560
_journal_page_last               1569
_journal_paper_doi               10.1039/C6SC04146A
_journal_volume                  8
_journal_year                    2017
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C31 H38 N2 O5'
_chemical_formula_sum            'C31 H38 N2 O5'
_chemical_formula_weight         518.63
_chemical_name_systematic        ysl-518-OBn-natural
_space_group_crystal_system      tetragonal
_space_group_IT_number           79
_space_group_name_Hall           'I 4'
_space_group_name_H-M_alt        'I 4'
_symmetry_space_group_name_Hall  'I 4'
_symmetry_space_group_name_H-M   'I 4'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_date             2016-04-19
_audit_creation_method
;
Olex2 1.2-beta
(compiled 2016.02.19 svn.r3266 for OlexSys, GUI svn.r5155)
;
_audit_update_record
;
2016-04-19 deposited with the CCDC.
2016-11-03 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   27.2685(8)
_cell_length_b                   27.2685(8)
_cell_length_c                   7.6863(3)
_cell_measurement_reflns_used    2231
_cell_measurement_temperature    100.0
_cell_measurement_theta_max      53.837
_cell_measurement_theta_min      2.292
_cell_volume                     5715.3(3)
_computing_cell_refinement       'SAINT v8.34A (Bruker, 2013)'
_computing_data_collection       'APEX2 v2014.9-0 (Bruker, 2014)'
_computing_data_reduction        'SAINT v8.34A (Bruker, 2013)'
_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      100.0
_diffrn_detector                 'Bruker APEX-II CCD'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            'CCD Area Detector'
_diffrn_measured_fraction_theta_full 0.992
_diffrn_measured_fraction_theta_max 0.992
_diffrn_measurement_device       'Kappa Four-Circle Diffractometer'
_diffrn_measurement_device_type  'Bruker X8 APEX II'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  'Double Bounce Multilayer Mirrors'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0507
_diffrn_reflns_av_unetI/netI     0.0493
_diffrn_reflns_Laue_measured_fraction_full 0.992
_diffrn_reflns_Laue_measured_fraction_max 0.992
_diffrn_reflns_limit_h_max       28
_diffrn_reflns_limit_h_min       -30
_diffrn_reflns_limit_k_max       31
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       8
_diffrn_reflns_limit_l_min       -8
_diffrn_reflns_number            13691
_diffrn_reflns_point_group_measured_fraction_full 0.973
_diffrn_reflns_point_group_measured_fraction_max 0.973
_diffrn_reflns_theta_full        63.241
_diffrn_reflns_theta_max         63.241
_diffrn_reflns_theta_min         2.291
_diffrn_source                   'Micro Focus Rotating Anode'
_diffrn_source_type              'Bruker FR-591'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.655
_exptl_absorpt_correction_T_max  0.3142
_exptl_absorpt_correction_T_min  0.2227
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2014/5 (Bruker,2014/5) was used for absorption correction.
wR2(int) was 0.0883 before and 0.0408 after correction.
The Ratio of minimum to maximum transmission is 0.7088.
The \l/2 correction factor is 0.00150.
;
_exptl_crystal_colour            white
_exptl_crystal_colour_primary    Colorless
_exptl_crystal_density_diffrn    1.205
_exptl_crystal_description       Needle
_exptl_crystal_F_000             2224
_exptl_crystal_recrystallization_method 'Vapour deposition'
_exptl_crystal_size_max          0.117
_exptl_crystal_size_mid          0.043
_exptl_crystal_size_min          0.021
_refine_diff_density_max         0.227
_refine_diff_density_min         -0.180
_refine_diff_density_rms         0.037
_refine_ls_abs_structure_details
;
 Flack x determined using 1210 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.0(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.027
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     471
_refine_ls_number_reflns         4523
_refine_ls_number_restraints     214
_refine_ls_restrained_S_all      1.022
_refine_ls_R_factor_all          0.0764
_refine_ls_R_factor_gt           0.0510
_refine_ls_shift/su_max          0.005
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0830P)^2^+0.2905P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1246
_refine_ls_wR_factor_ref         0.1399
_reflns_Friedel_coverage         0.810
_reflns_Friedel_fraction_full    0.951
_reflns_Friedel_fraction_max     0.951
_reflns_number_gt                3331
_reflns_number_total             4523
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c6sc04146a2.cif
_cod_data_source_block           Boger48
_cod_depositor_comments
;
The following automatic conversions were performed:

'_diffrn_radiation_probe' value 'X-ray' changed to 'x-ray' according
to
/usr/data/users/saulius/crontab/automatic-downloads/rss-feeds/RSC/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 4268 2015-11-12 08:31:59Z antanas 

 Adding full bibliography for 1544462--1544465.cif.

 Adding full bibliography for 1544462--1544465.cif.
;
_cod_original_cell_volume        5715.3(4)
_cod_database_code               1544464
_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
2. Uiso/Uaniso restraints and constraints
Uanis(C31B) = Uanis(C31)
3. Rigid body (RIGU) restrains
 O3, O3B, N2, N2B, C6, C7, C15, C16, C17, C18, C19, C20, C22, C30, C15B, C16B,
 C17B, C18B, C19B, C20B, C22B, C30B
 with sigma for 1-2 distances of 0.002 and sigma for 1-3 distances of 0.002
 O4, O5, O4B, O5B, C21, C31, C21B, C31B
 with sigma for 1-2 distances of 0.002 and sigma for 1-3 distances of 0.002
4. Others
 Fixed Sof: O3(0.6) O4(0.6) O5(0.6) O3B(0.4) O4B(0.4) O5B(0.4) N2(0.6)
 N2B(0.4) H7(0.6) H7B(0.4) C15(0.6) C16(0.6) C17(0.6) H17(0.6) C18(0.6)
 C19(0.6) H19(0.6) C20(0.6) H20(0.6) C21(0.6) C22(0.6) H22A(0.6) H22B(0.6)
 H22C(0.6) C30(0.6) H30A(0.6) H30B(0.6) H30C(0.6) C31(0.6) H31A(0.6) H31B(0.6)
 H31C(0.6) C15B(0.4) C16B(0.4) C17B(0.4) H17B(0.4) C18B(0.4) C19B(0.4)
 H19B(0.4) C20B(0.4) H20B(0.4) C21B(0.4) C22B(0.4) H22D(0.4) H22E(0.4)
 H22F(0.4) C30B(0.4) H30D(0.4) H30E(0.4) H30F(0.4) C31B(0.4) H31D(0.4)
 H31E(0.4) H31F(0.4)
5.a Ternary CH refined with riding coordinates:
 C5(H5), C7(H7), C7(H7B), C9(H9)
5.b Secondary CH2 refined with riding coordinates:
 C1(H1A,H1B), C10(H10A,H10B), C11(H11A,H11B), C13(H13A,H13B), C14(H14A,H14B),
 C23(H23A,H23B)
5.c Aromatic/amide H refined with riding coordinates:
 C2(H2), C3(H3), C25(H25), C26(H26), C27(H27), C28(H28), C29(H29), C17(H17),
 C19(H19), C20(H20), C17B(H17B), C19B(H19B), C20B(H20B)
5.d Idealised Me refined as rotating group:
 C12(H12A,H12B,H12C), C22(H22A,H22B,H22C), C30(H30A,H30B,H30C), C31(H31A,H31B,
 H31C), C22B(H22D,H22E,H22F), C30B(H30D,H30E,H30F), C31B(H31D,H31E,H31F)
5.e Idealised tetrahedral OH refined as rotating group:
 O1(H1)
;
_shelx_res_checksum              87557
_shelx_fab_checksum              65698
_shelx_shelxl_version_number     2014/7
_olex2_submission_special_instructions 'No special instructions were received'