Total synthesis, biological evaluation and biosynthetic re-evaluation of <i>Illicium</i>-derived neolignans.
Arnold, Robert E.; Saska, Jan; Mesquita-Ribeiro, Raquel; Dajas-Bailador, Federico; Taylor, Laurence; Lewis, William; Argent, Stephen; Shao, Huiling; Houk, Kendall N.; Denton, Ross M.; Chemical science 15 (2024) 11783–11793; doi:10.1039/d4sc03232b

data_1571944
_publ_section_title
;
 Total synthesis, biological evaluation and biosynthetic re-evaluation of
 <i>Illicium</i>-derived neolignans.
;
_journal_issue                   30
_journal_name_full               'Chemical science'
_journal_page_first              11783
_journal_page_last               11793
_journal_paper_doi               10.1039/d4sc03232b
_journal_volume                  15
_journal_year                    2024
_chemical_formula_moiety         'C29 H29.99 O4'
_chemical_formula_sum            'C29 H30 O4'
_chemical_formula_weight         442.53
_space_group_crystal_system      monoclinic
_space_group_IT_number           15
_space_group_name_Hall           '-I 2ya'
_space_group_name_H-M_alt        'I 1 2/a 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     iterative
_atom_sites_solution_secondary   difmap
_audit_creation_date             2017-11-24
_audit_creation_method
;
Olex2 1.2
(compiled 2017.08.10 svn.r3458 for OlexSys, GUI svn.r5381)
;
_audit_update_record
;
2024-01-23 deposited with the CCDC.	2024-06-13 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90.510(3)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   19.1851(6)
_cell_length_b                   7.8229(2)
_cell_length_c                   31.2872(11)
_cell_measurement_reflns_used    4865
_cell_measurement_temperature    120(2)
_cell_measurement_theta_max      74.0200
_cell_measurement_theta_min      4.6090
_cell_volume                     4695.5(3)
_computing_cell_refinement       'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_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    'olex2.solve (Bourhis et al., 2015)'
_diffrn_ambient_environment      'N2 gas'
_diffrn_ambient_temperature      120(2)
_diffrn_crystal_treatment        'flash frozen in gaseous N2'
_diffrn_detector                 'CCD area detector'
_diffrn_detector_area_resol_mean 4.2207
_diffrn_detector_type            'Agilent Diffraction Titan S2 detector'
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.970
_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     84.00 142.00   1.00   20.00    --  103.32  45.00 -60.00   58
  2  \w     60.00  90.00   1.00   20.00    --  103.32 -45.00-180.00   30
  3  \w     41.00  96.00   1.00   20.00    --  103.32 -45.00 -90.00   55
  4  \w     66.00  92.00   1.00   20.00    --  103.32 -45.00 -60.00   26
  5  \w     60.00  90.00   1.00   20.00    --  103.32 -30.00   0.00   30
  6  \w     37.00  87.00   1.00   20.00    --  103.32 -30.00  90.00   50
  7  \w     40.00  90.00   1.00   20.00    --  103.32 -45.00 150.00   50
  8  \w     63.00 121.00   1.00   20.00    --  103.32-125.00 120.00   58
  9  \w     37.00  90.00   1.00   20.00    --  103.32 -30.00 -30.00   53
 10  \w      2.00  28.00   1.00    5.00    --   43.06-125.00 -60.00   26
 11  \w     -8.00  28.00   1.00    5.00    --  -43.06  38.00-150.00   36
 12  \w    -47.00   3.00   1.00    5.00    --  -43.06  38.00  30.00   50
 13  \w   -111.00 -25.00   1.00    5.00    --  -43.06 -57.00  60.00   86
;
_diffrn_measurement_device       '\k-geometry diffractometer'
_diffrn_measurement_device_type  'SuperNova, Titan S2'
_diffrn_measurement_method       '\w scans'
_diffrn_measurement_specimen_support 'MiTeGen micromount'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0773638000
_diffrn_orient_matrix_UB_12      0.0528865000
_diffrn_orient_matrix_UB_13      -0.0006953000
_diffrn_orient_matrix_UB_21      0.0057813000
_diffrn_orient_matrix_UB_22      0.0552550000
_diffrn_orient_matrix_UB_23      0.0471981000
_diffrn_orient_matrix_UB_31      0.0206306000
_diffrn_orient_matrix_UB_32      0.1814784000
_diffrn_orient_matrix_UB_33      -0.0140735000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0230
_diffrn_reflns_av_unetI/netI     0.0263
_diffrn_reflns_Laue_measured_fraction_full 0.996
_diffrn_reflns_Laue_measured_fraction_max 0.970
_diffrn_reflns_limit_h_max       23
_diffrn_reflns_limit_h_min       -21
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -6
_diffrn_reflns_limit_l_max       38
_diffrn_reflns_limit_l_min       -37
_diffrn_reflns_number            9181
_diffrn_reflns_point_group_measured_fraction_full 0.996
_diffrn_reflns_point_group_measured_fraction_max 0.970
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.693
_diffrn_reflns_theta_min         2.825
_diffrn_source                   'microfocus sealed tube'
_diffrn_source_type              'Agilent Diffraction microfocus tube'
_exptl_absorpt_coefficient_mu    0.655
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.563
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.46 (Rigaku Oxford Diffraction, 2015)
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            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.252
_exptl_crystal_description       plate
_exptl_crystal_F_000             1888
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: diethyl ether, petroleum ether'
_exptl_crystal_size_max          0.32
_exptl_crystal_size_mid          0.283
_exptl_crystal_size_min          0.044
_refine_diff_density_max         0.489
_refine_diff_density_min         -0.255
_refine_diff_density_rms         0.040
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.040
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     387
_refine_ls_number_reflns         4611
_refine_ls_number_restraints     273
_refine_ls_restrained_S_all      1.079
_refine_ls_R_factor_all          0.0497
_refine_ls_R_factor_gt           0.0456
_refine_ls_shift/su_max          0.003
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0657P)^2^+2.9875P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1214
_refine_ls_wR_factor_ref         0.1261
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4160
_reflns_number_total             4611
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4sc03232b2.cif
_cod_data_source_block           44
_cod_depositor_comments
'Adding full bibliography for 1571943--1571950.cif.'
_cod_database_code               1571944
_nottingham_internal_coll_name   REARDE
_nottingham_internal_coll_number 17310
_nottingham_internal_coll_client REA/RD
_nottingham_internal_coll_type   custom
_nottingham_internal_coll_frame_method '\w scans'
_nottingham_internal_coll_frame_time '20.00, 5.00'
_nottingham_internal_coll_frame_width 1.00
_nottingham_internal_coll_user   pczwl
_nottingham_internal_coll_date   23/10/2017
_nottingham_internal_coll_location NOTTS
_nottingham_internal_coll_instrument 'GVA, PL13110002'
_nottingham_internal_process_date 24/10/2017
_nottingham_internal_process_user pczwl
_nottingham_internal_solution_date 24/10/2017
_nottingham_internal_solution_user pczwl
_nottingham_internal_refinement_date 20/11/2017
_nottingham_internal_refinement_user pczwl
_nottingham_internal_validation_date 24/11/2017
_nottingham_internal_validation_user pczwl
_nottingham_internal_archive_date 24/11/2017
_shelx_shelxl_version_number     2017/1
_chemical_oxdiff_formula         'C29 H30 O4'
_chemical_oxdiff_usercomment
'REARDE #17310 GVA-1298 IN FOMBLIN FILM ON A MICROMOUNT FOR REA/RD'
_shelx_estimated_absorpt_t_max   0.972
_shelx_estimated_absorpt_t_min   0.818
_reflns_odcompleteness_completeness 99.67
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     67.13
_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
 C20A-C19 \\sim C20-C19
 with sigma of 0.02
 C20-C21 \\sim C21A-C20A \\sim C21B-C20A
 with sigma of 0.02
 C30A-C26 \\sim C30-C26 \\sim C19-C9
 with sigma of 0.02
 C30B-C26 \\sim C30-C26 \\sim C26-C30A \\sim C19-C9
 with sigma of 0.02
 C31A-C32A \\sim C32-C31 \\sim C20-C21 \\sim C21A-C20A \\sim C21B-C20A
 with sigma of 0.02
 C21A-C20A \\sim C21B-C20A \\sim C20-C21 \\sim C32B-C31B \\sim C32-C31 \\sim
C31A-C32A
 with sigma of 0.02
 C20A-C19 \\sim C20-C19 \\sim C30A-C31A \\sim C30-C31
 with sigma of 0.02
 C20-C19 \\sim C20A-C19 \\sim C31B-C30B \\sim C30-C31 \\sim C31A-C30A
 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
C19 \\sim C20 \\sim C20A \\sim C21 \\sim C21A \\sim C21B \\sim C30 \\sim C30A
\\sim C30B \\sim C31 \\sim C31A \\sim C31B \\sim C32 \\sim C32A \\sim C32B:
within 2A with sigma of 0.01 and sigma for terminal atoms of 0.02
4. Rigid body (RIGU) restrains
 C19, C20, C20A, C21, C21A, C21B, C30, C30A, C30B, C31, C31A, C31B, C32, C32A,
 C32B
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
5. Others
 1*[Sof(H19A)+Sof(H19B)+Sof(H19C)+Sof(H19D)+Sof(C20)+Sof(H20)+Sof(C20A)+
 Sof(C21)+Sof(H21A)+Sof(H21B)]+1*[Sof(H20A)+Sof(C21A)+Sof(H21C)+Sof(H21D)]+1*
 [Sof(H20B)+Sof(C21B)+Sof(H21E)+Sof(H21F)]=1 with esd of 0.001
 1*[Sof(C30)+Sof(H30A)+Sof(H30B)+Sof(C31)+Sof(H31)+Sof(C32)+Sof(H32A)+
 Sof(H32B)]+1*[Sof(C30A)+Sof(H30C)+Sof(H30D)+Sof(C31A)+Sof(H31A)+Sof(C32A)+
 Sof(H32C)+Sof(H32D)]+1*[Sof(C30B)+Sof(H30E)+Sof(H30F)+Sof(C31B)+Sof(H31B)+
 Sof(C32B)+Sof(H32E)+Sof(H32F)]=1 with esd of 0.001
 Sof(C30)=Sof(H30A)=Sof(H30B)=Sof(C31)=Sof(H31)=Sof(C32)=Sof(H32A)=Sof(H32B)=
 FVAR(1)
 Sof(H19C)=Sof(H19D)=Sof(C20A)=1-FVAR(2)
 Sof(H19A)=Sof(H19B)=Sof(C20)=Sof(H20)=Sof(C21)=Sof(H21A)=Sof(H21B)=FVAR(2)
 Sof(H20A)=Sof(C21A)=Sof(H21C)=Sof(H21D)=FVAR(3)
 Sof(H20B)=Sof(C21B)=Sof(H21E)=Sof(H21F)=FVAR(4)
 Sof(C30A)=Sof(H30C)=Sof(H30D)=Sof(C31A)=Sof(H31A)=Sof(C32A)=Sof(H32C)=
 Sof(H32D)=FVAR(5)
 Sof(C30B)=Sof(H30E)=Sof(H30F)=Sof(C31B)=Sof(H31B)=Sof(C32B)=Sof(H32E)=
 Sof(H32F)=FVAR(6)
6.a Ternary CH refined with riding coordinates:
 C6(H6)
6.b Secondary CH2 refined with riding coordinates:
 C5(H5A,H5B), C17(H17A,H17B), C19(H19A,H19B), C19(H19C,H19D), C30(H30A,H30B),
 C30A(H30C,H30D), C30B(H30E,H30F)
6.c Aromatic/amide H refined with riding coordinates:
 C7(H7), C8(H8), C10(H10), C11(H11), C14(H14), C15(H15), C20(H20), C20A(H20A),
 C20A(H20B), C24(H24), C25(H25), C27(H27), C31(H31), C31A(H31A), C31B(H31B)
6.d X=CH2 refined with riding coordinates:
 C21(H21A,H21B), C21A(H21C,H21D), C21B(H21E,H21F), C32(H32A,H32B), C32A(H32C,
 H32D), C32B(H32E,H32F)
6.e Idealised Me refined as rotating group:
 C18(H18A,H18B,H18C), C29(H29A,H29B,H29C)
;
_shelx_res_checksum              4415
_shelx_hkl_checksum              94604
_olex2_date_sample_data_collection 2017-10-23
_olex2_date_sample_submission    2017-10-20
_olex2_exptl_crystal_mounting_method "'in fomblin film on a micromount"
_olex2_submission_original_sample_id RA-235-002
_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 1.159
_oxdiff_exptl_absorpt_empirical_full_min 0.868