Design strategy and preliminary antiproliferative investigation of a modified lignan skeleton derived from aryne and statin.
Lei, Yu; Wen, Yinshan; Xu, Xiaoliang; Hu, Qiong; Chang, Meng; Qiang, Ruihua; Hu, Yimin; Organic & biomolecular chemistry 22 (2024) 8263–8267; doi:10.1039/d4ob01264j

data_7160148
_publ_section_title
;
 Design strategy and preliminary antiproliferative investigation of a
 modified lignan skeleton derived from aryne and statin.
;
_journal_issue                   41
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              8263
_journal_page_last               8267
_journal_paper_doi               10.1039/d4ob01264j
_journal_volume                  22
_journal_year                    2024
_chemical_formula_moiety         'C46 H46 F2 O6'
_chemical_formula_sum            'C46 H46 F2 O6'
_chemical_formula_weight         732.83
_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   mixed
_atom_sites_solution_primary     dual
_atom_sites_solution_secondary   difmap
_audit_creation_date             2024-03-21
_audit_creation_method
;
Olex2 1.5
(compiled 2022.04.07 svn.rca3783a0 for OlexSys, GUI svn.r6498)
;
_audit_update_record
;
2024-03-21 deposited with the CCDC.	2024-09-17 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 95.6730(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   12.1596(8)
_cell_length_b                   12.2452(8)
_cell_length_c                   27.3069(18)
_cell_measurement_reflns_used    7602
_cell_measurement_temperature    293.15(10)
_cell_measurement_theta_max      22.549
_cell_measurement_theta_min      2.239
_cell_volume                     4046.0(5)
_computing_cell_refinement       'SAINT v8.34A (Bruker, 2013)'
_computing_data_collection       'Bruker SMART APEX II diffractometer'
_computing_data_reduction        'SAINT v8.34A (Bruker, 2013)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2019/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2014/4 (Sheldrick, 2014)'
_diffrn_ambient_temperature      293.15(10)
_diffrn_detector                 'CCD area detector'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            'CCD area detector'
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.997
_diffrn_measurement_device       'three-circle diffractometer'
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0323
_diffrn_reflns_av_unetI/netI     0.0520
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.997
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       32
_diffrn_reflns_limit_l_min       -31
_diffrn_reflns_number            31133
_diffrn_reflns_point_group_measured_fraction_full 0.990
_diffrn_reflns_point_group_measured_fraction_max 0.988
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         25.386
_diffrn_reflns_theta_min         1.499
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_current           30.0
_diffrn_source_power             1.5
_diffrn_source_target            Mo
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.085
_exptl_absorpt_correction_T_max  0.7452
_exptl_absorpt_correction_T_min  0.6839
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2014/5 (Bruker,2014/5) was used for absorption correction.
wR2(int) was 0.1299 before and 0.0538 after correction.
The Ratio of minimum to maximum transmission is 0.9177.
The \l/2 correction factor is 0.00150.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.203
_exptl_crystal_description       block
_exptl_crystal_F_000             1552
_exptl_crystal_size_max          0.24
_exptl_crystal_size_mid          0.23
_exptl_crystal_size_min          0.2
_refine_diff_density_max         0.289
_refine_diff_density_min         -0.220
_refine_diff_density_rms         0.038
_refine_ls_abs_structure_details
;
 Flack x determined using 3015 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.3(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.028
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     1210
_refine_ls_number_reflns         14703
_refine_ls_number_restraints     686
_refine_ls_restrained_S_all      1.076
_refine_ls_R_factor_all          0.1106
_refine_ls_R_factor_gt           0.0612
_refine_ls_shift/su_max          0.007
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1015P)^2^+0.1027P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1582
_refine_ls_wR_factor_ref         0.1907
_reflns_Friedel_coverage         0.888
_reflns_Friedel_fraction_full    0.982
_reflns_Friedel_fraction_max     0.979
_reflns_number_gt                8612
_reflns_number_total             14703
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4ob01264j2.cif
_cod_data_source_block           171102a
_cod_depositor_comments          'Adding full bibliography for 7160148.cif.'
_cod_database_code               7160148
_shelx_shelxl_version_number     2019/3
_shelx_estimated_absorpt_t_max   0.983
_shelx_estimated_absorpt_t_min   0.980
_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
2. Restrained distances
 C52A-C53A
 1.54 with sigma of 0.01
 C91-C89 = C92-C91 = C90-C89
 1.54 with sigma of 0.01
 C7A-C6A = C7-C6
 1.54 with sigma of 0.01
 C89-C92
 2.515 with sigma of 0.02
3. Rigid bond restraints
 C52, C53
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.02
4. Uiso/Uaniso restraints and constraints
O6 \\sim C42 \\sim C43 \\sim C44 \\sim C45 \\sim C46 \\sim O5 \\sim C42A \\sim
C43A \\sim C44A \\sim C45A \\sim C46A \\sim O5A: within 2A with sigma of 0.01
and sigma for terminal atoms of 0.02 within 2A
C52 \\sim C53: within 2A with sigma of 0.01 and sigma for terminal atoms of
0.02 within 2A
O11 \\sim C88 \\sim C89 \\sim C90 \\sim C91 \\sim C92 \\sim O12 \\sim C88A
\\sim C89A \\sim C90A \\sim C91A \\sim C92A \\sim O12A: within 2A with sigma of
0.01 and sigma for terminal atoms of 0.02 within 2A
C51 \\sim C52 \\sim C53 \\sim O9 \\sim O10 \\sim C52A \\sim C53A \\sim O9A
\\sim O10A: within 2A with sigma of 0.01 and sigma for terminal atoms of 0.02
within 2A
C5 \\sim C6 \\sim C7 \\sim O3 \\sim O4 \\sim C6A \\sim C7A \\sim O3A \\sim O4A:
within 2A with sigma of 0.01 and sigma for terminal atoms of 0.02 within 2A
C3 \\sim C1 \\sim C2 \\sim O1 \\sim O2 \\sim C1A \\sim C2A \\sim O1A \\sim O2A:
within 2A with sigma of 0.01 and sigma for terminal atoms of 0.02 within 2A
5. Same fragment restrains
{C3, C1A, C2A, O1A, O2A} sigma for 1-2: 0.01, 1-3: 0.04
as in
{C3, C1, C2, O1, O2}
{C5, C6A, C7A, O3A, O4A} sigma for 1-2: 0.01, 1-3: 0.04
as in
{C5, C6, C7, O3, O4}
{O6, C42A, C43A, C44A, C45A, C46A, O5A} sigma for 1-2: 0.01, 1-3: 0.04
as in
{O6, C42, C43, C44, C45, C46, O5}
{C51, C52A, C53A, O9A, O10A} sigma for 1-2: 0.01, 1-3: 0.04
as in
{C51, C52, C53, O9, O10}
{O11, C88A, C89A, C90A, C91A, C92A, O12A} sigma for 1-2: 0.01, 1-3: 0.04
as in
{O11, C88, C89, C90, C91, C92, O12}
6. Others
 Sof(C88A)=Sof(C89A)=Sof(H89A)=Sof(C90A)=Sof(H90D)=Sof(H90E)=Sof(H90F)=
 Sof(C91A)=Sof(H91C)=Sof(H91D)=Sof(C92A)=Sof(H92D)=Sof(H92E)=Sof(H92F)=
 Sof(O12A)=1-FVAR(1)
 Sof(C88)=Sof(C89)=Sof(H89)=Sof(C90)=Sof(H90A)=Sof(H90B)=Sof(H90C)=Sof(C91)=
 Sof(H91A)=Sof(H91B)=Sof(C92)=Sof(H92A)=Sof(H92B)=Sof(H92C)=Sof(O12)=FVAR(1)
 Sof(C42A)=Sof(C43A)=Sof(H43A)=Sof(C44A)=Sof(H44D)=Sof(H44E)=Sof(H44F)=
 Sof(C45A)=Sof(H45C)=Sof(H45D)=Sof(C46A)=Sof(H46D)=Sof(H46E)=Sof(H46F)=Sof(O5A)=
 1-FVAR(2)
 Sof(C42)=Sof(C43)=Sof(H43)=Sof(C44)=Sof(H44A)=Sof(H44B)=Sof(H44C)=Sof(C45)=
 Sof(H45A)=Sof(H45B)=Sof(C46)=Sof(H46A)=Sof(H46B)=Sof(H46C)=Sof(O5)=FVAR(2)
 Sof(C52A)=Sof(H52C)=Sof(H52D)=Sof(C53A)=Sof(H53D)=Sof(H53E)=Sof(H53F)=
 Sof(O9A)=Sof(O10A)=1-FVAR(3)
 Sof(C52)=Sof(H52A)=Sof(H52B)=Sof(C53)=Sof(H53A)=Sof(H53B)=Sof(H53C)=Sof(O9)=
 Sof(O10)=FVAR(3)
 Sof(C6A)=Sof(H6AA)=Sof(H6AB)=Sof(C7A)=Sof(H7AA)=Sof(H7AB)=Sof(H7AC)=Sof(O3A)=
 Sof(O4A)=1-FVAR(4)
 Sof(C6)=Sof(H6A)=Sof(H6B)=Sof(C7)=Sof(H7A)=Sof(H7B)=Sof(H7C)=Sof(O3)=Sof(O4)=
 FVAR(4)
 Sof(C1A)=Sof(H1AA)=Sof(H1AB)=Sof(H1AC)=Sof(C2A)=Sof(H2AA)=Sof(H2AB)=Sof(O1A)=
 Sof(O2A)=1-FVAR(5)
 Sof(C1)=Sof(H1A)=Sof(H1B)=Sof(H1C)=Sof(C2)=Sof(H2A)=Sof(H2B)=Sof(O1)=Sof(O2)=
 FVAR(5)
 Fixed Z: C45A(0.772789)
7.a Riding coordinates:
 C90(H90A,H90B,H90C), C44A(H44D,H44E,H44F)
7.b Ternary CH refined with riding coordinates:
 C31(H31), C32(H32), C39(H39), C43(H43), C77(H77), C78(H78), C85(H85),
 C89(H89), C43A(H43A), C89A(H89A)
7.c Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C6(H6A,H6B), C8(H8A,H8B), C15(H15A,H15B), C40(H40A,H40B),
 C45(H45A,H45B), C2A(H2AA,H2AB), C6A(H6AA,H6AB), C48(H48A,H48B), C52(H52A,H52B),
  C54(H54A,H54B), C61(H61A,H61B), C86(H86A,H86B), C91(H91A,H91B), C45A(H45C,
 H45D), C52A(H52C,H52D), C91A(H91C,H91D)
7.d Aromatic/amide H refined with riding coordinates:
 C11(H11), C19(H19), C20(H20), C22(H22), C23(H23), C25(H25), C26(H26),
 C28(H28), C29(H29), C34(H34), C35(H35), C37(H37), C57(H57), C65(H65), C66(H66),
  C68(H68), C69(H69), C71(H71), C72(H72), C74(H74), C75(H75), C80(H80),
 C81(H81), C83(H83)
7.e Idealised Me refined as rotating group:
 C1(H1A,H1B,H1C), C7(H7A,H7B,H7C), C30(H30A,H30B,H30C), C41(H41A,H41B,H41C),
 C44(H44A,H44B,H44C), C46(H46A,H46B,H46C), C1A(H1AA,H1AB,H1AC), C7A(H7AA,H7AB,
 H7AC), C47(H47A,H47B,H47C), C53(H53A,H53B,H53C), C76(H76A,H76B,H76C), C87(H87A,
 H87B,H87C), C92(H92A,H92B,H92C), C46A(H46D,H46E,H46F), C53A(H53D,H53E,H53F),
 C90A(H90D,H90E,H90F), C92A(H92D,H92E,H92F)
;
_olex2_submission_special_instructions 'No special instructions were received'