Biomimetic synthesis of dispiro sesquiterpene lactone type alkaloids and discovery of potential anticancer scaffolds
Guo, Dong-Gui; Zhang, Sijie; Liu, Lin-Lu; Cen, Hong-Xing; Liu, Xiong-Li; Wang, Hui-Juan; Peng, Li-Jun; New Journal of Chemistry 50 (2026) 3225–3238; doi:10.1039/D5NJ04317D

data_7064274
_publ_section_title
;
 Biomimetic synthesis of dispiro sesquiterpene lactone type alkaloids and
 discovery of potential anticancer scaffolds
;
_journal_issue                   7
_journal_name_full               'New Journal of Chemistry'
_journal_page_first              3225
_journal_page_last               3238
_journal_paper_doi               10.1039/D5NJ04317D
_journal_volume                  50
_journal_year                    2026
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C28 H33 F N2 O4'
_chemical_formula_sum            'C28 H33 F N2 O4'
_chemical_formula_weight         480.56
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_audit_creation_date             2024-04-21
_audit_creation_method
;
Olex2 1.5-beta
(compiled 2022.04.07 svn.rca3783a0 for OlexSys, GUI svn.r6439)
;
_audit_update_record
;
2025-10-19 deposited with the CCDC.	2026-01-12 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   11.07456(8)
_cell_length_b                   19.22227(13)
_cell_length_c                   23.30686(16)
_cell_measurement_reflns_used    26088
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      73.2360
_cell_measurement_theta_min      2.3560
_cell_volume                     4961.52(6)
_computing_cell_refinement       'CrysAlisPro 1.171.43.92a (Rigaku OD, 2023)'
_computing_data_collection
'CrysAlisPro system (CCD 43.92a 64-bit (release 05-10-2023))'
_computing_data_reduction        'CrysAlisPro 1.171.43.92a (Rigaku OD, 2023)'
_computing_molecular_graphics    'Olex2 1.5-beta (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5-beta (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXS  (Sheldrick, 2008)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.00(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.981
_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    -26.00  71.00   0.50    0.10    --   45.87 -79.00 -43.00  194
  2  \w    -25.00  29.00   0.50    0.10    --   45.87 -19.00  30.00  108
  3  \w    -25.00   7.00   0.50    0.10    --   45.87 -19.00 -30.00   64
  4  \w     27.00  53.00   0.50    0.16    --   99.00 -45.00-120.00   52
  5  \w     26.00  55.00   0.50    0.16    --   99.00 -61.00  60.00   58
  6  \w     27.00  52.00   0.50    0.16    --   99.00 -45.00 120.00   50
  7  \w     26.00  52.00   0.50    0.16    --   99.00 -51.00 165.00   52
  8  \w     39.00 107.00   0.50    0.16    --   99.00 -77.00 150.00  136
  9  \w     27.00  52.00   0.50    0.16    --   99.00 -45.00  30.00   50
 10  \w     27.00  52.00   0.50    0.16    --   99.00 -45.00-150.00   50
 11  \w    127.00 159.00   0.50    0.16    --   99.00  61.00-120.00   64
 12  \w     81.00 171.00   0.50    0.16    --   99.00  15.00  30.00  180
 13  \w     89.00 172.00   0.50    0.16    --   99.00  51.00 -48.00  166
 14  \w   -103.00 -76.00   0.50    0.16    --  -99.00  77.00  30.00   54
 15  \w    -69.00 -37.00   0.50    0.16    --  -99.00  77.00  30.00   64
 16  \w    -66.00 -26.00   0.50    0.16    --  -99.00  61.00   0.00   80
 17  \w    -64.00 -28.00   0.50    0.16    --  -99.00  61.00  30.00   72
 18  \w    -51.00 -26.00   0.50    0.16    --  -99.00  61.00  60.00   50
 19  \w    -79.00 -42.00   0.50    0.16    --  -99.00  79.00  80.00   74
 20  \w   -115.00 -88.00   0.50    0.16    --  -99.00  79.00  80.00   54
 21  \w    -56.00 -31.00   0.50    0.16    --  -99.00  51.00 -48.00   50
 22  \w    -21.00  27.00   0.50    0.10    --  -45.87  37.00-120.00   96
 23  \w    -12.00  14.00   0.50    0.10    --  -45.87  19.00 -90.00   52
 24  \w   -106.00 -76.00   0.50    0.16    --  -99.00  96.00 175.00   60
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy R, DW system, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0453334000
_diffrn_orient_matrix_UB_12      0.0648180000
_diffrn_orient_matrix_UB_13      -0.0323984000
_diffrn_orient_matrix_UB_21      0.0744395000
_diffrn_orient_matrix_UB_22      0.0215902000
_diffrn_orient_matrix_UB_23      0.0529155000
_diffrn_orient_matrix_UB_31      0.1083584000
_diffrn_orient_matrix_UB_32      -0.0419394000
_diffrn_orient_matrix_UB_33      -0.0228069000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0343
_diffrn_reflns_av_unetI/netI     0.0296
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.981
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -23
_diffrn_reflns_limit_l_max       28
_diffrn_reflns_limit_l_min       -28
_diffrn_reflns_number            33378
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.969
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.374
_diffrn_reflns_theta_min         2.980
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.742
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.59763
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.43.92a (Rigaku Oxford Diffraction, 2023)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'metallic dark colourless'
_exptl_crystal_density_diffrn    1.287
_exptl_crystal_description       block
_exptl_crystal_F_000             2048
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.139
_refine_diff_density_min         -0.216
_refine_diff_density_rms         0.037
_refine_ls_abs_structure_details
;
 Flack x determined using 3945 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.08(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.043
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     637
_refine_ls_number_reflns         9661
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.043
_refine_ls_R_factor_all          0.0311
_refine_ls_R_factor_gt           0.0296
_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^)+(0.0352P)^2^+0.7302P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0709
_refine_ls_wR_factor_ref         0.0718
_reflns_Friedel_coverage         0.783
_reflns_Friedel_fraction_full    0.995
_reflns_Friedel_fraction_max     0.954
_reflns_number_gt                9273
_reflns_number_total             9661
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5nj04317d2.cif
_cod_data_source_block           dt-8-no
_cod_database_code               7064274
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C H O N F'
_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.a Ternary CH refined with riding coordinates:
 C8(H8), C9(H9), C14(H14), C28(H28), C38(H38), C41(H41), C47(H47), C50(H50)
2.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C3(H3A,H3B), C4(H4A,H4B), C10(H10A,H10B), C13(H13A,H13B),
 C15(H15A,H15B), C16(H16A,H16B), C17(H17A,H17B), C42(H42A,H42B), C43(H43A,H43B),
  C44(H44A,H44B), C46(H46A,H46B), C49(H49A,H49B), C51(H51A,H51B), C52(H52A,
 H52B), C53(H53A,H53B)
2.c Aromatic/amide H refined with riding coordinates:
 C7(H7), C21(H21), C23(H23), C24(H24), C39(H39), C58(H58), C59(H59), C61(H61)
2.d Idealised Me refined as rotating group:
 C26(H26A,H26B,H26C), C27(H27A,H27B,H27C), C29(H29A,H29B,H29C), C67(H67A,H67B,
 H67C), C69(H69A,H69B,H69C), C70(H70A,H70B,H70C)
;
_shelx_res_checksum              24318
_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 1.518
_oxdiff_exptl_absorpt_empirical_full_min 0.326