Synthesis and structure-activity relationship studies of novel tubulysin U analogues - effect on cytotoxicity of structural variations in the tubuvaline fragment.
Shankar, Sreejith P.; Jagodzinska, Monika; Malpezzi, Luciana; Lazzari, Paolo; Manca, Ilaria; Greig, Iain R.; Sani, Monica; Zanda, Matteo; Organic & biomolecular chemistry 11 (2013) 2273–2287; doi:10.1039/c3ob27111k

data_7152849
_publ_section_title
;
 Synthesis and structure-activity relationship studies of novel tubulysin
 U analogues - effect on cytotoxicity of structural variations in the
 tubuvaline fragment.
;
_journal_issue                   14
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              2273
_journal_page_last               2287
_journal_paper_doi               10.1039/c3ob27111k
_journal_volume                  11
_journal_year                    2013
_chemical_formula_moiety         'C27 H43 N O4'
_chemical_formula_sum            'C27 H43 N O4'
_chemical_formula_weight         445.62
_chemical_name_common
2-isopropyl-5-methylcyclohexyl-4-(tert-butoxycarbonylamino)-2-methyl-5-phenylpentanoate
_chemical_name_systematic
2-isopropyl-5-methylcyclohexyl-4-(tert-butoxycarbonylamino)-2-methyl-5-phenylpentanoate
_space_group_IT_number           19
_symmetry_cell_setting           orthorhombic
_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_creation_method           SHELXL-97
_cell_angle_alpha                90.00
_cell_angle_beta                 90.00
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   9.862(2)
_cell_length_b                   10.080(2)
_cell_length_c                   27.249(6)
_cell_measurement_reflns_used    88
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      28.23
_cell_measurement_theta_min      6.48
_cell_volume                     2708.8(10)
_computing_cell_refinement       'XSCANS (Siemens, 1996)'
_computing_data_collection       'XSCANS (Siemens, 1996)'
_computing_data_reduction        'XSCANS (Siemens, 1996)'
_computing_molecular_graphics    'SHELXTL/PC (Sheldrick, 1996)'
_computing_publication_material  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SIR97 (Altomare et al.,1999)'
_diffrn_ambient_temperature      293(2)
_diffrn_measured_fraction_theta_full 0.954
_diffrn_measured_fraction_theta_max 0.955
_diffrn_measurement_device_type  \q/2\q
_diffrn_measurement_method       'Siemens P4 diffractometer'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54179
_diffrn_reflns_av_R_equivalents  0.0365
_diffrn_reflns_av_sigmaI/netI    0.0422
_diffrn_reflns_limit_h_max       2
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -1
_diffrn_reflns_limit_l_max       32
_diffrn_reflns_limit_l_min       -1
_diffrn_reflns_number            3316
_diffrn_reflns_theta_full        64.99
_diffrn_reflns_theta_max         64.99
_diffrn_reflns_theta_min         3.24
_diffrn_standards_decay_%        0.5
_diffrn_standards_interval_count 200
_diffrn_standards_number         3
_exptl_absorpt_coefficient_mu    0.568
_exptl_absorpt_correction_type   none
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.093
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       prism
_exptl_crystal_F_000             976
_exptl_crystal_size_max          0.90
_exptl_crystal_size_mid          0.40
_exptl_crystal_size_min          0.40
_refine_diff_density_max         0.172
_refine_diff_density_min         -0.201
_refine_diff_density_rms         0.041
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.1(3)
_refine_ls_extinction_coef       0.0025(4)
_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   1.072
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     302
_refine_ls_number_reflns         3101
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.072
_refine_ls_R_factor_all          0.0591
_refine_ls_R_factor_gt           0.0477
_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^)+(0.0797P)^2^+0.0967P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1207
_refine_ls_wR_factor_ref         0.1301
_reflns_number_gt                2615
_reflns_number_total             3101
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            c3ob27111k.txt
_cod_data_source_block           gf324a
_cod_original_sg_symbol_H-M      P212121
_cod_database_code               7152849