Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids
Huseman, Eric D.; Byl, Jo Ann W.; Chapp, Scott M.; Schley, Nathan D.; Osheroff, Neil; Townsend, Steven D.; ACS Central Science  (2021) –; doi:10.1021/acscentsci.1c00040

data_4518917
_publ_section_title
;
 Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin
 and Doxorubicin Hybrids
;
_journal_name_full               'ACS Central Science'
_journal_paper_doi               10.1021/acscentsci.1c00040
_journal_year                    2021
_chemical_absolute_configuration rmad
_chemical_formula_moiety         'C42 H66 N4 O13 Si2'
_chemical_formula_sum            'C42 H66 N4 O13 Si2'
_chemical_formula_weight         891.16
_chemical_name_systematic
'4-nitrobenzyl ((2S,3S,4S,6R)-6-((tert-butyldimethylsilyl)oxy)-3-(((2S,4S,5R,6S)-4-((tert-butyldimethylsilyl)oxy)-4,6-dimethyl-5-((((4-nitrobenzyl)oxy)carbonyl)amino)tetrahydro-2H-pyran-2-yl)oxy)-2,4-dimethyltetrahydro-2H-pyran-4-yl)carbamate'
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2020-06-11
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2020-11-07 deposited with the CCDC.	2020-11-15 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 94.4773(13)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   8.02112(11)
_cell_length_b                   11.95004(14)
_cell_length_c                   24.8127(4)
_cell_measurement_reflns_used    13329
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      73.2030
_cell_measurement_theta_min      3.5540
_cell_volume                     2371.11(6)
_computing_cell_refinement       'CrysAlisPro 1.171.40.69a (Rigaku OD, 2020)'
_computing_data_collection       'CrysAlisPro 1.171.40.69a (Rigaku OD, 2020)'
_computing_data_reduction        'CrysAlisPro 1.171.40.69a (Rigaku OD, 2020)'
_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_environment      N~2~
_diffrn_ambient_temperature      100.00(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 8.1506
_diffrn_detector_type            EosS2
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.994
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w   -104.00 -20.00   1.00    2.00    --  -37.09 -57.00  30.00   84
  2  \w    -90.00  -2.00   1.00    2.00    --  -37.09 125.00-150.00   88
  3  \w   -104.00 -20.00   1.00    2.00    --  -37.09 -57.00  90.00   84
  4  \w   -104.00 -20.00   1.00    2.00    --  -37.09 -57.00 -60.00   84
  5  \w     23.00  90.00   1.00    2.00    --   37.09-125.00-120.00   67
  6  \w     18.00 106.00   1.00    2.00    --   37.09  38.00 -90.00   88
  7  \w     42.00 109.00   1.00    7.00    --  111.00 -94.00 150.00   67
  8  \w     94.00 178.00   1.00    7.00    --  111.00  45.00 -30.00   84
  9  \w     93.00 178.00   1.00    7.00    --  111.00  61.00 -60.00   85
 10  \w     44.00 129.00   1.00    7.00    --  111.00 -61.00  60.00   85
 11  \w     43.00 128.00   1.00    7.00    --  111.00 -45.00 150.00   85
 12  \w     93.00 178.00   1.00    7.00    --  111.00  61.00-150.00   85
 13  \w    100.00 178.00   1.00    7.00    --  111.00 111.00 150.00   78
 14  \w     43.00 138.00   1.00    7.00    --  111.00 -77.00-180.00   95
 15  \w    100.00 178.00   1.00    7.00    --  111.00 111.00-180.00   78
 16  \w     43.00 128.00   1.00    7.00    --  111.00 -45.00  30.00   85
 17  \w   -105.00 -10.00   1.00    2.00    --  -37.09 -77.00-120.00   95
 18  \w    -54.00  30.00   1.00    2.00    --  -37.09  57.00-180.00   84
 19  \w   -105.00 -10.00   1.00    2.00    --  -37.09 -77.00-180.00   95
 20  \w    -30.00  54.00   1.00    2.00    --   37.09 -57.00 -30.00   84
 21  \w     -8.00  72.00   1.00    2.00    --   37.09 -91.00  94.00   80
 22  \w     73.00 178.00   1.00    7.00    --  111.00  15.00  60.00  105
 23  \w     90.00 178.00   1.00    7.00    --  111.00  30.00 120.00   88
 24  \w     90.00 176.00   1.00    7.00    --  111.00  30.00-180.00   86
 25  \w     41.00 116.00   1.00    7.00    --  111.00-111.00   0.00   75
 26  \w     90.00 178.00   1.00    7.00    --  111.00  30.00 -90.00   88
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, EosS2'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0756877000
_diffrn_orient_matrix_UB_12      -0.1028874000
_diffrn_orient_matrix_UB_13      -0.0302425000
_diffrn_orient_matrix_UB_21      0.0212109000
_diffrn_orient_matrix_UB_22      0.0582981000
_diffrn_orient_matrix_UB_23      -0.0544438000
_diffrn_orient_matrix_UB_31      0.1758505000
_diffrn_orient_matrix_UB_32      -0.0513438000
_diffrn_orient_matrix_UB_33      -0.0011118000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0275
_diffrn_reflns_av_unetI/netI     0.0330
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.994
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       30
_diffrn_reflns_limit_l_min       -30
_diffrn_reflns_number            24066
_diffrn_reflns_point_group_measured_fraction_full 0.991
_diffrn_reflns_point_group_measured_fraction_max 0.970
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.445
_diffrn_reflns_theta_min         3.574
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.215
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.494
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.69a (Rigaku Oxford Diffraction, 2020)
Numerical absorption correction based on gaussian integration over
			a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.248
_exptl_crystal_description       plate
_exptl_crystal_F_000             956
_exptl_crystal_size_max          0.386
_exptl_crystal_size_mid          0.215
_exptl_crystal_size_min          0.026
_refine_diff_density_max         0.395
_refine_diff_density_min         -0.208
_refine_diff_density_rms         0.035
_refine_ls_abs_structure_details
;
 Flack x determined using 3877 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.014(16)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.026
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     564
_refine_ls_number_reflns         9230
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.026
_refine_ls_R_factor_all          0.0338
_refine_ls_R_factor_gt           0.0321
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0453P)^2^+0.4427P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0812
_refine_ls_wR_factor_ref         0.0822
_reflns_Friedel_coverage         0.858
_reflns_Friedel_fraction_full    0.981
_reflns_Friedel_fraction_max     0.943
_reflns_number_gt                8869
_reflns_number_total             9230
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            oc1c00040_si_003.cif
_cod_data_source_block           edh-e-0823_c1f21-25
_cod_original_cell_volume        2371.10(5)
_cod_database_code               4518917
_shelx_shelxl_version_number     2018/1
_chemical_oxdiff_formula         C42H66N4O13Si2
_reflns_odcompleteness_completeness 99.96
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     69.95
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Ternary CH refined with riding coordinates:
 C1(H1A), C4(H4), C5(H5), C8(H8), C11(H11), C12(H12)
2.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C10(H10A,H10B), C16(H16A,H16B), C30(H30A,H30B)
2.c Aromatic/amide H refined with riding coordinates:
 N1(H1), N2(H2), C18(H18), C19(H19), C21(H21), C22(H22), C32(H32), C33(H33),
 C35(H35), C36(H36)
2.d Idealised Me refined as rotating group:
 C6(H6A,H6B,H6C), C7(H7A,H7B,H7C), C13(H13A,H13B,H13C), C14(H14A,H14B,H14C),
 C23(H23A,H23B,H23C), C24(H24A,H24B,H24C), C26(H26A,H26B,H26C), C27(H27A,H27B,
 H27C), C28(H28A,H28B,H28C), C37(H37A,H37B,H37C), C38(H38A,H38B,H38C), C40(H40A,
 H40B,H40C), C41(H41A,H41B,H41C), C42(H42A,H42B,H42C)
;
_shelx_res_checksum              66306
_shelx_hkl_checksum              20645
_olex2_date_sample_data_collection 2019-10-02
_olex2_exptl_crystal_mounting_method 'mounted in a polyimide loop'
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.247
_oxdiff_exptl_absorpt_empirical_full_min 0.809