Design and Concise Synthesis of Halicyclamine-Inspired Bismacrocycles Targeting DedA Membrane Proteins
Wayama, Toshiaki; Horinouchi, Riku; Arai, Masayoshi; Ohashi, Hirofumi; Watashi, Koichi; Yoshida, Satoshi; Sato, Sota; Tsukamoto, Sachiko; Oguri, Hiroki; Chemical Communications  (2026) –; doi:10.1039/D6CC01052K

data_7135724
_publ_section_title
;
 Design and concise synthesis of halicyclamine-inspired bis-macrocycles
 targeting DedA membrane proteins.
;
_journal_issue                   35
_journal_name_full               'Chemical communications (Cambridge, England)'
_journal_page_first              9011
_journal_page_last               9015
_journal_paper_doi               10.1039/d6cc01052k
_journal_volume                  62
_journal_year                    2026
_chemical_formula_moiety         'C28 H38 N2 O4'
_chemical_formula_sum            'C28 H38 N2 O4'
_chemical_formula_weight         466.60
_chemical_name_systematic        260312Wayama
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2026-03-30
_audit_creation_method
;
Olex2 1.5
(compiled 2025.07.13 svn.rb7424aed for OlexSys, GUI svn.r7314)
;
_audit_update_record
;
2026-04-03 deposited with the CCDC.	2026-04-10 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 102.641(6)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   12.507(2)
_cell_length_b                   13.541(2)
_cell_length_c                   14.653(3)
_cell_measurement_reflns_used    1776
_cell_measurement_temperature    109.00
_cell_measurement_theta_max      20.47
_cell_measurement_theta_min      2.25
_cell_volume                     2421.4(7)
_computing_cell_refinement       'SAINT V8.40B (Bruker, 2016)'
_computing_data_collection       'APEX5 v2023.9-4 (Bruker, 2023)'
_computing_data_reduction        'SAINT V8.40B (Bruker, 2016)'
_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 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      109.00
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.1661
_diffrn_reflns_av_unetI/netI     0.0790
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       17
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            44522
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.999
_diffrn_reflns_theta_full        25.093
_diffrn_reflns_theta_max         25.093
_diffrn_reflns_theta_min         1.942
_diffrn_source_current           1.4
_diffrn_source_power             0.07
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.085
_exptl_absorpt_correction_T_max  0.7138
_exptl_absorpt_correction_T_min  0.6673
_exptl_absorpt_correction_type   none
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016) was used for absorption correction.
wR2(int) was 0.1381 before and 0.0964 after correction.
The Ratio of minimum to maximum transmission is 0.9349.
The \l/2 correction factor is Not present.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.280
_exptl_crystal_description       plate
_exptl_crystal_F_000             1008
_exptl_crystal_preparation       'vapor diffusion'
_exptl_crystal_size_max          0.248
_exptl_crystal_size_mid          0.234
_exptl_crystal_size_min          0.116
_refine_diff_density_max         0.483
_refine_diff_density_min         -0.448
_refine_diff_density_rms         0.065
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.039
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     316
_refine_ls_number_reflns         4296
_refine_ls_number_restraints     2
_refine_ls_restrained_S_all      1.041
_refine_ls_R_factor_all          0.1187
_refine_ls_R_factor_gt           0.0615
_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^)+(0.0609P)^2^+3.3325P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1354
_refine_ls_wR_factor_ref         0.1876
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2534
_reflns_number_total             4296
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d6cc01052k2.cif
_cod_data_source_block           260312wayama
_cod_depositor_comments
'Adding full bibliography for 7135724--7135725.cif.'
_cod_original_cell_volume        2421.6(7)
_cod_database_code               7135724
_shelx_shelxl_version_number     2019/3
_shelx_estimated_absorpt_t_max   0.990
_shelx_estimated_absorpt_t_min   0.979
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All C(H,H,H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 C15-C17 \\sim C15-C16
 with sigma of 0.01
 C17-C18 \\sim C16-C18
 with sigma of 0.01
3. Others
 Sof(H15C)=Sof(H15D)=Sof(H18C)=Sof(H18D)=Sof(C16)=Sof(H16A)=Sof(H16B)=1-FVAR(1)
 Sof(H15A)=Sof(H15B)=Sof(C17)=Sof(H17A)=Sof(H17B)=Sof(H18A)=Sof(H18B)=FVAR(1)
4.a Ternary CH refined with riding coordinates:
 C8(H8)
4.b Secondary CH2 refined with riding coordinates:
 C9(H9A,H9B), C23(H23A,H23B), C15(H15A,H15B), C15(H15C,H15D), C28(H28A,H28B),
 C24(H24A,H24B), C25(H25A,H25B), C21(H21A,H21B), C17(H17A,H17B), C18(H18A,H18B),
  C18(H18C,H18D), C16(H16A,H16B)
4.c Aromatic/amide H refined with riding coordinates:
 C13(H13), C3(H3), C1(H1), C27(H27), C19(H19), C20(H20), C26(H26)
4.d Idealised Me refined as rotating group:
 C11(H11A,H11B,H11C), C7(H7A,H7B,H7C), C6(H6A,H6B,H6C), C12(H12A,H12B,H12C)
;
_shelx_res_checksum              45408
_shelx_hkl_checksum              45465
_olex2_exptl_crystal_mounting_method manual
_olex2_submission_original_sample_id 260312Wayama
_olex2_submission_special_instructions 'No special instructions were received'