Design, synthesis, and duplex-stabilizing properties of conformationally constrained tricyclic analogues of LNA.
Giacometti, Robert D.; Salinas, Juan C.; Østergaard, Michael E; Swayze, Eric E.; Seth, Punit P.; Hanessian, Stephen; Organic & biomolecular chemistry 14 (2016) 2034–2040; doi:10.1039/c5ob02576a

data_7154914
_publ_section_title
;
 Design, synthesis, and duplex-stabilizing properties of conformationally
 constrained tricyclic analogues of LNA.
;
_journal_issue                   6
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              2034
_journal_page_last               2040
_journal_paper_doi               10.1039/c5ob02576a
_journal_volume                  14
_journal_year                    2016
_chemical_absolute_configuration syn
_chemical_compound_source        'Synthesized by the authors. See text.'
_chemical_formula_moiety         'C40 H35 N3 O10'
_chemical_formula_sum            'C40 H35 N3 O10'
_chemical_formula_weight         717.71
_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'
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_audit_creation_date             2015-10-28
_audit_creation_method
;
Olex2 1.2
(compiled 2015.09.30 svn.r3233 for OlexSys, GUI svn.r5103)
;
_audit_update_record
;
2015-11-02 deposited with the CCDC.
2016-01-14 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 113.4900(10)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   14.2003(3)
_cell_length_b                   7.6452(2)
_cell_length_c                   17.2049(4)
_cell_measurement_reflns_used    6968
_cell_measurement_temperature    100.15
_cell_measurement_theta_max      70.29
_cell_measurement_theta_min      2.80
_cell_volume                     1713.05(7)
_computing_cell_refinement       'SAINT v7.60A (Bruker, 2009)'
_computing_data_reduction        'SAINT v7.60A (Bruker, 2009)'
_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    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_temperature      100.15
_diffrn_detector                 'Bruker APEX2 area detector'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            'CCD area detector'
_diffrn_measured_fraction_theta_full 0.965
_diffrn_measured_fraction_theta_max 0.950
_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           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0289
_diffrn_reflns_av_unetI/netI     0.0611
_diffrn_reflns_Laue_measured_fraction_full 0.965
_diffrn_reflns_Laue_measured_fraction_max 0.950
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -17
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            10927
_diffrn_reflns_point_group_measured_fraction_full 0.939
_diffrn_reflns_point_group_measured_fraction_max 0.916
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         70.682
_diffrn_reflns_theta_min         2.800
_diffrn_source                   'microfocus sealed X-ray tube'
_diffrn_source_type              'Incoatec I\muS Microsource'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.838
_exptl_absorpt_correction_T_max  0.9705
_exptl_absorpt_correction_T_min  0.8190
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2007/4 (Bruker,2007) was used for absorption correction.
wR2(int) was 0.0652 before and 0.0290 after correction.
The Ratio of minimum to maximum transmission is 0.8439.
The \l/2 correction factor is not present.
;
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.391
_exptl_crystal_description       block
_exptl_crystal_F_000             752
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: Ethyl acetate/petroleum ether (65--110 \%C)'
_exptl_crystal_size_max          0.11
_exptl_crystal_size_mid          0.04
_exptl_crystal_size_min          0.02
_refine_diff_density_max         0.500
_refine_diff_density_min         -0.286
_refine_diff_density_rms         0.062
_refine_ls_abs_structure_details
;
 Flack x determined using 1642 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.15(14)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.974
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     541
_refine_ls_number_reflns         6032
_refine_ls_number_restraints     342
_refine_ls_restrained_S_all      1.000
_refine_ls_R_factor_all          0.0693
_refine_ls_R_factor_gt           0.0555
_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^)+(0.0821P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1381
_refine_ls_wR_factor_ref         0.1437
_reflns_Friedel_coverage         0.786
_reflns_Friedel_fraction_full    0.909
_reflns_Friedel_fraction_max     0.877
_reflns_number_gt                4622
_reflns_number_total             6032
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c5ob02576a2.cif
_cod_data_source_block           ben102
_cod_depositor_comments
'Adding full bibliography for 7154913--7154914.cif.'
_cod_database_code               7154914
_shelx_estimated_absorpt_t_max   0.983
_shelx_estimated_absorpt_t_min   0.913
_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
 N2A-C33A \\sim N2B-C33B
 with sigma of 0.02
 C33A-O10A \\sim C33B-O10B
 with sigma of 0.02
 O10A-C34A \\sim O10B-C34B
 with sigma of 0.02
 C34A-C35A \\sim C34B-C35B
 with sigma of 0.02
 C10A-C33A \\sim C10B-C33B
 with sigma of 0.02
 C11A-C33A \\sim C11B-C33B
 with sigma of 0.02
 N2A-O10A \\sim N2B-O10B
 with sigma of 0.02
 C33A-C34A \\sim C33B-C34B
 with sigma of 0.02
 O10A-C35A \\sim O10B-C35B
 with sigma of 0.02
 C34A-C36A \\sim C34B-C36B \\sim C34A-C40A \\sim C34B-C40B
 with sigma of 0.02
 N2A-C10A \\sim N2B-C10B
 with sigma of 0.02
 N2A-C11A \\sim N2B-C11B
 with sigma of 0.02
 N2A-N1 \\sim N2B-N1
 with sigma of 0.02
 N2A-C12A \\sim N2B-C12B
 with sigma of 0.02
 O9A-C11A \\sim O9B-C11B
 with sigma of 0.02
 O9A-N2A \\sim O9B-N2B
 with sigma of 0.02
 O9A-C12A \\sim O9B-C12B
 with sigma of 0.02
 O8A-C10A \\sim O8B-C10B
 with sigma of 0.02
 O8A-N2A \\sim O8B-N2B
 with sigma of 0.02
 O8A-N1 \\sim O8B-N1
 with sigma of 0.02
 C11A-C10A \\sim C11B-C10B
 with sigma of 0.02
 C10A-N1 \\sim C10B-N1
 with sigma of 0.02
 C11A-C12A \\sim C11B-C12B
 with sigma of 0.02
 C10A-C13A \\sim C10B-C13B
 with sigma of 0.02
 C11A-C13A \\sim C11B-C13B
 with sigma of 0.02
 C12A-C13A \\sim C12B-C13B
 with sigma of 0.02
 C14A-C12A \\sim C14B-C12B
 with sigma of 0.02
 C13A-N1 \\sim C13B-N1
 with sigma of 0.02
 C12A-N1 \\sim C12B-N1
 with sigma of 0.02
 C16A-C17A \\sim C16B-C17B \\sim C17A-C18A \\sim C17B-C18B \\sim C18A-C19A
\\sim C18B-C19B \\sim C19A-
 C20A \\sim C19B-C20B \\sim C20A-C21A \\sim C20B-C21B \\sim C21A-C22A \\sim
C21B-C22B \\sim C22A-C23A ~
 C22B-C23B \\sim C23A-C24A \\sim C23B-C24B \\sim C24A-C25A \\sim C24B-C25B
\\sim C25A-C16A \\sim C25B-
 C16B \\sim C18A-C23A \\sim C18B-C23B
 with sigma of 0.005
 C15A-C16A \\sim C15B-C16B
 with sigma of 0.008
 C16A-C18A \\sim C16B-C18B
 with sigma of 0.02
 C17A-C19A \\sim C17B-C19B \\sim C22A-C24A \\sim C22B-C24B
 with sigma of 0.008
 C18A-C20A \\sim C18B-C20B \\sim C21A-C23A \\sim C21B-C23B
 with sigma of 0.008
 C19A-C21A \\sim C19B-C21B
 with sigma of 0.02
 C20A-C22A \\sim C20B-C22B
 with sigma of 0.02
 C23A-C25A \\sim C23B-C25B
 with sigma of 0.02
 C24A-C16A \\sim C24B-C16B
 with sigma of 0.02
 C25A-C17A \\sim C25B-C17B
 with sigma of 0.02
 C19A-C23A \\sim C19B-C23B \\sim C18A-C22A \\sim C18B-C22B
 with sigma of 0.01
 C17A-C23A \\sim C17B-C23B \\sim C18A-C24A \\sim C18B-C24A
 with sigma of 0.01
 C15A-C25A \\sim C15B-C25B
 with sigma of 0.008
 C15A-C17A \\sim C15B-C17B
 with sigma of 0.008
 O3-C15A \\sim O3-C15B
 with sigma of 0.005
 C15A-C3 \\sim C15B-C3
 with sigma of 0.02
 O3-C16A \\sim O3-C16B
 with sigma of 0.02
3. Restrained planarity
 C34A, C35A, C36A, C37A, C38A, C39A, C40A
 with sigma of 0.1
 C34B, C35B, C36B, C37B, C38B, C39B, C40B
 with sigma of 0.1
 C33B, N2B, C10B, N1, C13B, C12B, C11B, C14B, O8B, O9B
 with sigma of 0.1
 C33A, N2A, C10A, N1, C13A, C12A, C11A, C14A, O8A, O9A
 with sigma of 0.1
 C15A, C16A, C17A, C18A, C19A, C20A, C21A, C22A, C23A, C24A, C25A
 with sigma of 0.1
 C15B, C16B, C17B, C18B, C19B, C20B, C21B, C22B, C23B, C24B, C25B
 with sigma of 0.001
4. Rigid bond restraints
 C24A, C25A
 with sigma for 1-2 distances of 0.005 and sigma for 1-3 distances of 0.005
 C18A, C19A
 with sigma for 1-2 distances of 0.005 and sigma for 1-3 distances of 0.005
5. Uiso/Uaniso restraints and constraints
Uanis(C13A) = Uanis(C13B)
Uanis(C12A) = Uanis(C12B)
Uanis(C14A) = Uanis(C14B)
Uanis(C11A) = Uanis(C11B)
Uanis(O9A) = Uanis(O9B)
Uanis(N2A) = Uanis(N2B)
Uanis(C10A) = Uanis(C10B)
Uanis(O8A) = Uanis(O8B)
Uanis(C33A) = Uanis(C33B)
Uanis(O10A) = Uanis(O10B)
Uanis(C34A) = Uanis(C34B)
Uanis(C35A) = Uanis(C35B)
Uanis(C36A) = Uanis(C36B)
Uanis(C37A) = Uanis(C37B)
Uanis(C38A) = Uanis(C38B)
Uanis(C39A) = Uanis(C39B)
Uanis(C40A) = Uanis(C40B)
Uanis(C15A) = Uanis(C15B)
Uanis(C16A) = Uanis(C16B)
Uanis(C17A) = Uanis(C17B)
Uanis(C18A) = Uanis(C18B)
Uanis(C19A) = Uanis(C19B)
Uanis(C20A) = Uanis(C20B)
Uanis(C21A) = Uanis(C21B)
Uanis(C22A) = Uanis(C22B)
Uanis(C23A) = Uanis(C23B)
Uanis(C24A) = Uanis(C24B)
Uanis(C25A) = Uanis(C25B)
6. Others
 Sof(O8B)=Sof(O9B)=Sof(O10B)=Sof(N2B)=Sof(C10B)=Sof(C11B)=Sof(C12B)=Sof(C13B)=
 Sof(H13B)=Sof(C14B)=Sof(H14D)=Sof(H14E)=Sof(H14F)=Sof(C15B)=Sof(H15C)=
 Sof(H15D)=Sof(C16B)=Sof(C17B)=Sof(H17B)=Sof(C18B)=Sof(C19B)=Sof(H19B)=
 Sof(C20B)=Sof(H20B)=Sof(C21B)=Sof(H21B)=Sof(C22B)=Sof(H22B)=Sof(C23B)=
 Sof(C24B)=Sof(H24B)=Sof(C25B)=Sof(H25B)=Sof(C33B)=Sof(H33C)=Sof(H33D)=
 Sof(C34B)=Sof(H34C)=Sof(H34D)=Sof(C35B)=Sof(C36B)=Sof(H36B)=Sof(C37B)=
 Sof(H37B)=Sof(C38B)=Sof(H38B)=Sof(C39B)=Sof(H39B)=Sof(C40B)=Sof(H40B)=1-FVAR(1)
 Sof(O8A)=Sof(O9A)=Sof(O10A)=Sof(N2A)=Sof(C10A)=Sof(C11A)=Sof(C12A)=Sof(C13A)=
 Sof(H13A)=Sof(C14A)=Sof(H14A)=Sof(H14B)=Sof(H14C)=Sof(C15A)=Sof(H15A)=
 Sof(H15B)=Sof(C16A)=Sof(C17A)=Sof(H17A)=Sof(C18A)=Sof(C19A)=Sof(H19A)=
 Sof(C20A)=Sof(H20A)=Sof(C21A)=Sof(H21A)=Sof(C22A)=Sof(H22A)=Sof(C23A)=
 Sof(C24A)=Sof(H24A)=Sof(C25A)=Sof(H25A)=Sof(C33A)=Sof(H33A)=Sof(H33B)=
 Sof(C34A)=Sof(H34A)=Sof(H34B)=Sof(C35A)=Sof(C36A)=Sof(H36A)=Sof(C37A)=
 Sof(H37A)=Sof(C38A)=Sof(H38A)=Sof(C39A)=Sof(H39A)=Sof(C40A)=Sof(H40A)=FVAR(1)
7.a Ternary CH refined with riding coordinates:
 C1(H1), C2(H2), C3(H3), C5(H5), C9(H9)
7.b Secondary CH2 refined with riding coordinates:
 C8(H8A,H8B), C15A(H15A,H15B), C33A(H33A,H33B), C34A(H34A,H34B), C15B(H15C,
 H15D), C33B(H33C,H33D), C34B(H34C,H34D)
7.c Aromatic/amide H refined with riding coordinates:
 C6(H6), C7(H7), C28(H28), C29(H29), C31(H31), C32(H32), C13A(H13A),
 C17A(H17A), C19A(H19A), C20A(H20A), C21A(H21A), C22A(H22A), C24A(H24A),
 C25A(H25A), C36A(H36A), C37A(H37A), C38A(H38A), C39A(H39A), C40A(H40A),
 C13B(H13B), C17B(H17B), C19B(H19B), C20B(H20B), C21B(H21B), C22B(H22B),
 C24B(H24B), C25B(H25B), C36B(H36B), C37B(H37B), C38B(H38B), C39B(H39B),
 C40B(H40B)
7.d Fitted hexagon refined as free rotating group:
 C35A(C36A,C37A,C38A,C39A,C40A), C35B(C36B,C37B,C38B,C39B,C40B)
7.e Idealised Me refined as rotating group:
 C14A(H14A,H14B,H14C), C14B(H14D,H14E,H14F)
;
_shelx_res_checksum              34342
_shelx_shelxl_version_number     2014/7
_olex2_submission_special_instructions 'No special instructions were received'