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_7135725
_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 H34 N2 O8'
_chemical_formula_sum            'C28 H34 N2 O8'
_chemical_formula_weight         526.57
_space_group_crystal_system      monoclinic
_space_group_IT_number           15
_space_group_name_Hall           '-C 2yc'
_space_group_name_H-M_alt        'C 1 2/c 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2026-04-02
_audit_creation_method
;
Olex2 1.5-ac7-022
(compiled 2026.02.09 svn.ra45a96f9 for Rigaku Oxford Diffraction, GUI svn.r7493)
;
_audit_update_record
;
2026-04-03 deposited with the CCDC.	2026-04-10 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 122.968(19)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   23.609(7)
_cell_length_b                   7.549(2)
_cell_length_c                   17.523(5)
_cell_measurement_reflns_used    4019
_cell_measurement_temperature    95(2)
_cell_measurement_theta_max      32.830
_cell_measurement_theta_min      2.604
_cell_volume                     2620.1(14)
_computing_cell_refinement       'XDS (Kabsch, 2010)'
_computing_data_collection       'KEK UGUIS'
_computing_data_reduction        'XDS (Kabsch, 2010)'
_computing_molecular_graphics    'Olex2 1.5-ac7-022 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5-ac7-022 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2025/1 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT-2018/2 (Sheldrick, 2015)'
_diffrn_ambient_temperature      95.15
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_diffrn_measurement_device_type  'Dectris Eiger X16M'
_diffrn_measurement_method       '\w scan'
_diffrn_radiation_type           synchrotron
_diffrn_radiation_wavelength     0.9000
_diffrn_reflns_av_R_equivalents  0.0944
_diffrn_reflns_av_unetI/netI     0.0428
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       28
_diffrn_reflns_limit_h_min       -28
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            29400
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 1.000
_diffrn_reflns_theta_full        32.684
_diffrn_reflns_theta_max         32.830
_diffrn_reflns_theta_min         2.604
_diffrn_source                   'KEK PF BL-17A'
_exptl_absorpt_coefficient_mu    0.173
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.697
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'XDS (Kabsch, 2010)'
_exptl_crystal_colour            yellow
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.335
_exptl_crystal_description       block
_exptl_crystal_F_000             1120
_exptl_crystal_size_max          0.01
_exptl_crystal_size_mid          0.01
_exptl_crystal_size_min          0.01
_refine_diff_density_max         0.213
_refine_diff_density_min         -0.230
_refine_diff_density_rms         0.042
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.041
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     335
_refine_ls_number_reflns         2393
_refine_ls_number_restraints     364
_refine_ls_restrained_S_all      1.051
_refine_ls_R_factor_all          0.0937
_refine_ls_R_factor_gt           0.0672
_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^)+(0.1299P)^2^+1.0029P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2045
_refine_ls_wR_factor_ref         0.2240
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1632
_reflns_number_total             2393
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d6cc01052k2.cif
_cod_data_source_block           tw4_2_data02_04merged_c
_cod_depositor_comments
'Adding full bibliography for 7135724--7135725.cif.'
_cod_database_code               7135725
_shelx_shelxl_version_number     2025/1
_shelx_estimated_absorpt_t_max   0.998
_shelx_estimated_absorpt_t_min   0.998
_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
 N1C-C1A = N1D-C1B
 1.47 with sigma of 0.01
 C1A-C2A = C1B-C2B
 1.5 with sigma of 0.02
 C2A-O1A = C2B-O1B
 1.21 with sigma of 0.01
 C2A-O2A
 1.4 with sigma of 0.002
 C2B-O2B
 1.4 with sigma of 0.002
 O2A-C3A = O2B-C3B
 1.43 with sigma of 0.02
 C3A-C4A = C3B-C4B
 1.5 with sigma of 0.02
 C4A-C5A = C4B-C5B
 1.32 with sigma of 0.02
 C5A-C6A = C5B-C6B
 1.5 with sigma of 0.01
 C6A-O3A = C6B-O3B
 1.43 with sigma of 0.01
 O3A-C7A
 1.4 with sigma of 0.006
 O3B-C7B
 1.4 with sigma of 0.004
 C7A-O4A = C7B-O4B
 1.21 with sigma of 0.01
 C7A-C6D = C7B-C6C
 1.5 with sigma of 0.01
 C6A-C7A
 2.6 with sigma of 0.01
3. Uiso/Uaniso restraints and constraints
N1C \\sim C1A \\sim C2A \\sim O1A \\sim N1D \\sim C1B \\sim C2B: within 2A with
sigma of 0.01 and sigma for terminal atoms of 0.02 within 2A
Uanis(C6B) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(O1A) = Uanis(O1B)
Uanis(O2A) = Uanis(O2B)
4. Rigid body (RIGU) restrains
 All non-hydrogen atoms
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Others
 Fixed Sof: C1A(0.5) H1AA(0.5) H1AB(0.5) C2A(0.5) O1A(0.5) O2A(0.5) C3A(0.5)
 H3AA(0.5) H3AB(0.5) C4A(0.5) H4A(0.5) C5A(0.5) H5A(0.5) C6A(0.5) H6AA(0.5)
 H6AB(0.5) O3A(0.5) C7A(0.5) O4A(0.5) C1B(0.5) H1BA(0.5) H1BB(0.5) C2B(0.5)
 O1B(0.5) O2B(0.5) C3B(0.5) H3BA(0.5) H3BB(0.5) C4B(0.5) H4B(0.5) C5B(0.5)
 H5B(0.5) C6B(0.5) H6BA(0.5) H6BB(0.5) O3B(0.5) C7B(0.5) O4B(0.5) N1C(0.5)
 C1C(0.5) C2C(0.5) H2CA(0.5) H2CB(0.5) H2CC(0.5) C3C(0.5) H3CA(0.5) H3CB(0.5)
 H3CC(0.5) C4C(0.5) H4CA(0.5) H4CB(0.5) C5C(0.5) H5C(0.5) C6C(0.5) C7C(0.5)
 H7C(0.5) N1D(0.5) C1D(0.5) C2D(0.5) H2DA(0.5) H2DB(0.5) H2DC(0.5) C3D(0.5)
 H3DA(0.5) H3DB(0.5) H3DC(0.5) C4D(0.5) C5D(0.5) H5D(0.5) C6D(0.5) C7D(0.5)
 H7D(0.5)
6.a Ternary CH refined with riding coordinates:
 C5C(H5C)
6.b Secondary CH2 refined with riding coordinates:
 C1A(H1AA,H1AB), C3A(H3AA,H3AB), C6A(H6AA,H6AB), C1B(H1BA,H1BB), C3B(H3BA,
 H3BB), C6B(H6BA,H6BB), C4C(H4CA,H4CB)
6.c Aromatic/amide H refined with riding coordinates:
 C4A(H4A), C5A(H5A), C4B(H4B), C5B(H5B), C7C(H7C), C5D(H5D), C7D(H7D)
6.d Idealised Me refined as rotating group:
 C2C(H2CA,H2CB,H2CC), C3C(H3CA,H3CB,H3CC), C2D(H2DA,H2DB,H2DC), C3D(H3DA,H3DB,
 H3DC)
;
_shelx_res_checksum              29390
_shelx_hkl_checksum              92915
_olex2_submission_special_instructions 'No special instructions were received'