# Supplementary Information (SI) for RSC Medicinal Chemistry.
# This journal is © The Royal Society of Chemistry 2025

####################################################################### 
# 
# This file contains crystal structure data downloaded from the 
# Cambridge Structural Database (CSD) hosted by the Cambridge 
# Crystallographic Data Centre (CCDC).
# 
# Full information about CCDC data access policies and citation 
# guidelines are available at http://www.ccdc.cam.ac.uk/access/V1 
# 
# Audit and citation data items may have been added by the CCDC. 
# Please retain this information to preserve the provenance of 
# this file and to allow appropriate attribution of the data. 
# 
#######################################################################

data_tiancj
_database_code_depnum_ccdc_archive 'CCDC 2101906'
loop_
_audit_author_name
_audit_author_address
'zhenyuan wang'
;Shenzhen Shinesky Biological Technology 
China
;
_audit_update_record             
;
2021-08-06 deposited with the CCDC.	2025-02-04 downloaded from the CCDC.
;
_audit_creation_date             2018-10-18
_audit_creation_method           
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_shelx_SHELXL_version_number     2018/3
_chemical_name_common            ?
_chemical_name_systematic        ?
_chemical_formula_moiety         'C7 H6 O3, C5 H11 N O2'
_chemical_formula_sum            'C12 H17 N O5'
_chemical_formula_weight         255.26
_chemical_melting_point          ?
loop_
_atom_type_symbol
_atom_type_description
_atom_type_scat_dispersion_real
_atom_type_scat_dispersion_imag
_atom_type_scat_source
C C 0.0033 0.0016 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
H H 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
N N 0.0061 0.0033 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
O O 0.0106 0.0060 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'

_shelx_space_group_comment       
;
The symmetry employed for this shelxl refinement is uniquely defined
by the following loop, which should always be used as a source of
symmetry information in preference to the above space-group names.
They are only intended as comments.
;
_space_group_crystal_system      orthorhombic
_space_group_IT_number           61
_space_group_name_H-M_alt        'P b c a'
_space_group_name_Hall           '-P 2ac 2ab'
loop_
_space_group_symop_operation_xyz
'x, y, z'
'-x+1/2, -y, z+1/2'
'-x, y+1/2, -z+1/2'
'x+1/2, -y+1/2, -z'
'-x, -y, -z'
'x-1/2, y, -z-1/2'
'x, -y-1/2, z-1/2'
'-x-1/2, y-1/2, z'

_cell_length_a                   10.2107(8)
_cell_length_b                   10.7746(8)
_cell_length_c                   22.5314(17)
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_volume                     2478.8(3)
_cell_formula_units_Z            8
_cell_measurement_reflns_used    3549
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      28.2160
_cell_measurement_theta_min      2.7100
_shelx_estimated_absorpt_T_max   0.989
_shelx_estimated_absorpt_T_min   0.987
_exptl_absorpt_coefficient_mu    0.107
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.76290
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   
;
CrysAlisPro 1.171.38.43f (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_absorpt_special_details   ?
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.368
_exptl_crystal_density_meas      ?
_exptl_crystal_density_method    ?
_exptl_crystal_description       block
_exptl_crystal_F_000             1088
_exptl_crystal_size_max          0.12
_exptl_crystal_size_mid          0.11
_exptl_crystal_size_min          0.1
_exptl_transmission_factor_max   ?
_exptl_transmission_factor_min   ?
_diffrn_reflns_av_R_equivalents  0.0466
_diffrn_reflns_av_unetI/netI     0.0464
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.896
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       30
_diffrn_reflns_limit_l_min       -29
_diffrn_reflns_number            12746
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.896
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         29.590
_diffrn_reflns_theta_min         2.692
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.00(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.2684
_diffrn_detector_type            AtlasS2
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.896
_diffrn_measurement_details      
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  tₑₓₚ   ω     θ     κ     φ   Frames
#--------------------------------------------------------------------------
  1  ω    -34.00  59.00   1.00    8.00    --  -11.59  57.00 120.00   93
  2  ω     47.00  82.00   1.00    8.00    --   11.74 178.00 -30.00   35
  3  ω    -16.00  59.00   1.00    8.00    --   11.74  77.00-120.00   75
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, AtlasS2'
_diffrn_measurement_method       'ω scans'
_diffrn_orient_matrix_type       
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0203027000
_diffrn_orient_matrix_UB_12      0.0033958000
_diffrn_orient_matrix_UB_13      -0.0300605000
_diffrn_orient_matrix_UB_21      -0.0661575000
_diffrn_orient_matrix_UB_22      0.0067382000
_diffrn_orient_matrix_UB_23      -0.0090031000
_diffrn_orient_matrix_UB_31      0.0057557000
_diffrn_orient_matrix_UB_32      0.0654269000
_diffrn_orient_matrix_UB_33      0.0024817000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Mo) X-ray Source'
_reflns_Friedel_coverage         0.000
_reflns_Friedel_fraction_full    .
_reflns_Friedel_fraction_max     .
_reflns_number_gt                2404
_reflns_number_total             3120
_reflns_odcompleteness_completeness 99.48
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.32
_reflns_special_details          
;
 Reflections were merged by SHELXL according to the crystal
 class for the calculation of statistics and refinement.
 
 _reflns_Friedel_fraction is defined as the number of unique
 Friedel pairs measured divided by the number that would be
 possible theoretically, ignoring centric projections and
 systematic absences.
;
_reflns_threshold_expression     'I > 2σ(I)'
_computing_cell_refinement       'CrysAlisPro 1.171.38.43f (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.43f (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.43f (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    'ShelXT (Sheldrick, 2015)'
_refine_diff_density_max         0.276
_refine_diff_density_min         -0.263
_refine_diff_density_rms         0.055
_refine_ls_extinction_coef       .
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.089
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     171
_refine_ls_number_reflns         3120
_refine_ls_number_restraints     1
_refine_ls_R_factor_all          0.0658
_refine_ls_R_factor_gt           0.0465
_refine_ls_restrained_S_all      1.095
_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/[σ²(Fo²)+(0.0425P)²+0.5388P] where P=(Fo²+2Fc²)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0997
_refine_ls_wR_factor_ref         0.1117
_refine_special_details          ?
_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, All O(H) groups
2. Restrained distances
 O3-H4
 0.82 with sigma of 0.02
3.a Secondary CH2 refined with riding coordinates:
 C9(H9A,H9B)
3.b Aromatic/amide H refined with riding coordinates:
 C6(H6), C3(H3), C5(H5), C4(H4A)
3.c Idealised Me refined as rotating group:
 C10(H10A,H10B,H10C), C11(H11A,H11B,H11C), C12(H12A,H12B,H12C)
3.d Idealised tetrahedral OH refined as rotating group:
 O1(H1)
;
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_atom_sites_solution_secondary   ?
loop_
_atom_site_label
_atom_site_type_symbol
_atom_site_fract_x
_atom_site_fract_y
_atom_site_fract_z
_atom_site_U_iso_or_equiv
_atom_site_adp_type
_atom_site_occupancy
_atom_site_site_symmetry_order
_atom_site_calc_flag
_atom_site_refinement_flags_posn
_atom_site_refinement_flags_adp
_atom_site_refinement_flags_occupancy
_atom_site_disorder_assembly
_atom_site_disorder_group
O2 O 0.35563(10) 0.72277(10) 0.41115(5) 0.0196(3) Uani 1 1 d . . . . .
O4 O 0.20754(10) 0.47682(9) 0.45729(5) 0.0207(3) Uani 1 1 d . . . . .
O3 O 0.38212(10) 0.52418(10) 0.38586(5) 0.0213(3) Uani 1 1 d D . . . .
O5 O 0.32546(10) 0.36647(10) 0.52328(5) 0.0218(3) Uani 1 1 d . . . . .
O1 O 0.47999(11) 0.89441(9) 0.35717(5) 0.0232(3) Uani 1 1 d . . . . .
H1 H 0.430618 0.864470 0.382054 0.035 Uiso 1 1 calc GR . . . .
N1 N 0.08384(12) 0.28293(11) 0.57915(5) 0.0150(3) Uani 1 1 d . . . . .
C1 C 0.49783(13) 0.67685(13) 0.33129(6) 0.0153(3) Uani 1 1 d . . . . .
C8 C 0.22221(14) 0.40498(13) 0.50254(6) 0.0173(3) Uani 1 1 d . . . . .
C2 C 0.53014(14) 0.80264(14) 0.32308(6) 0.0173(3) Uani 1 1 d . . . . .
C7 C 0.40562(14) 0.64066(14) 0.37967(6) 0.0163(3) Uani 1 1 d . . . . .
C6 C 0.55373(14) 0.58882(14) 0.29362(6) 0.0183(3) Uani 1 1 d . . . . .
H6 H 0.532897 0.505486 0.298758 0.022 Uiso 1 1 calc R . . . .
C9 C 0.08842(14) 0.37364(14) 0.52872(6) 0.0170(3) Uani 1 1 d . . . . .
H9A H 0.048592 0.450421 0.542112 0.020 Uiso 1 1 calc R . . . .
H9B H 0.034043 0.341340 0.496975 0.020 Uiso 1 1 calc R . . . .
C10 C -0.05746(14) 0.26998(14) 0.59643(7) 0.0196(3) Uani 1 1 d . . . . .
H10A H -0.090012 0.348617 0.609991 0.029 Uiso 1 1 calc GR . . . .
H10B H -0.065328 0.209855 0.627672 0.029 Uiso 1 1 calc GR . . . .
H10C H -0.107429 0.243199 0.562690 0.029 Uiso 1 1 calc GR . . . .
C3 C 0.61805(14) 0.83630(15) 0.27834(6) 0.0199(3) Uani 1 1 d . . . . .
H3 H 0.640377 0.919265 0.273095 0.024 Uiso 1 1 calc R . . . .
C5 C 0.63924(15) 0.62225(15) 0.24890(7) 0.0213(3) Uani 1 1 d . . . . .
H5 H 0.674511 0.562409 0.223815 0.026 Uiso 1 1 calc R . . . .
C4 C 0.67182(15) 0.74682(16) 0.24192(7) 0.0222(3) Uani 1 1 d . . . . .
H4A H 0.730518 0.770018 0.212374 0.027 Uiso 1 1 calc R . . . .
C11 C 0.15733(16) 0.33014(16) 0.63164(7) 0.0231(4) Uani 1 1 d . . . . .
H11A H 0.248730 0.335993 0.622053 0.035 Uiso 1 1 calc GR . . . .
H11B H 0.145803 0.274149 0.664369 0.035 Uiso 1 1 calc GR . . . .
H11C H 0.124806 0.410703 0.642318 0.035 Uiso 1 1 calc GR . . . .
C12 C 0.13375(16) 0.15863(14) 0.55999(7) 0.0246(4) Uani 1 1 d . . . . .
H12A H 0.083301 0.129608 0.526818 0.037 Uiso 1 1 calc GR . . . .
H12B H 0.125915 0.100870 0.592234 0.037 Uiso 1 1 calc GR . . . .
H12C H 0.224054 0.165670 0.548612 0.037 Uiso 1 1 calc GR . . . .
H4 H 0.322(2) 0.505(3) 0.4159(10) 0.086(9) Uiso 1 1 d D . . . .


_geom_special_details            
;
 All esds (except the esd in the dihedral angle between two l.s. planes)
 are estimated using the full covariance matrix.  The cell esds are taken
 into account individually in the estimation of esds in distances, angles
 and torsion angles; correlations between esds in cell parameters are only
 used when they are defined by crystal symmetry.  An approximate (isotropic)
 treatment of cell esds is used for estimating esds involving l.s. planes.
;
loop_
_geom_bond_atom_site_label_1
_geom_bond_atom_site_label_2
_geom_bond_distance
_geom_bond_site_symmetry_2
_geom_bond_publ_flag
O2 C7 1.2436(17) . ?
O4 C8 1.2888(18) . ?
O3 C7 1.2853(18) . ?
O5 C8 1.2255(17) . ?
O1 C2 1.3528(18) . ?
N1 C9 1.4996(18) . ?
N1 C10 1.5009(19) . ?
N1 C11 1.4902(19) . ?
N1 C12 1.4966(18) . ?
C1 C2 1.407(2) . ?
C1 C7 1.492(2) . ?
C1 C6 1.395(2) . ?
C8 C9 1.526(2) . ?
C2 C3 1.398(2) . ?
C6 C5 1.381(2) . ?
C3 C4 1.380(2) . ?
C5 C4 1.392(2) . ?

loop_
_geom_angle_atom_site_label_1
_geom_angle_atom_site_label_2
_geom_angle_atom_site_label_3
_geom_angle
_geom_angle_site_symmetry_1
_geom_angle_site_symmetry_3
_geom_angle_publ_flag
C9 N1 C10 106.69(11) . . ?
C11 N1 C9 111.30(12) . . ?
C11 N1 C10 108.05(11) . . ?
C11 N1 C12 111.29(12) . . ?
C12 N1 C9 110.73(11) . . ?
C12 N1 C10 108.60(11) . . ?
C2 C1 C7 119.71(13) . . ?
C6 C1 C2 118.63(13) . . ?
C6 C1 C7 121.67(13) . . ?
O4 C8 C9 109.55(12) . . ?
O5 C8 O4 127.22(14) . . ?
O5 C8 C9 123.23(13) . . ?
O1 C2 C1 122.73(13) . . ?
O1 C2 C3 117.58(13) . . ?
C3 C2 C1 119.69(14) . . ?
O2 C7 O3 123.79(13) . . ?
O2 C7 C1 119.32(13) . . ?
O3 C7 C1 116.88(13) . . ?
C5 C6 C1 121.69(14) . . ?
N1 C9 C8 117.72(12) . . ?
C4 C3 C2 120.20(15) . . ?
C6 C5 C4 119.02(15) . . ?
C3 C4 C5 120.77(14) . . ?


_olex2_date_sample_data_collection 2018-10-18
_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
- Detector area scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.381
_oxdiff_exptl_absorpt_empirical_full_min 0.740
