# Electronic Supplementary Material (ESI) for ChemComm.
# This journal is © The Royal Society of Chemistry 2021

####################################################################### 
# 
# 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_s1
_database_code_depnum_ccdc_archive 'CCDC 2048176'
loop_
_audit_author_name
_audit_author_address
'Erich Altenhofer'
;Arrowhead Pharmaceuticals 
United States of America
;
_audit_update_record             
;
2020-12-03 deposited with the CCDC.	2021-06-15 downloaded from the CCDC.
;
_audit_creation_date             2020-06-08
_audit_creation_method           
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_shelx_SHELXL_version_number     2017/1
_chemical_name_common            ?
_chemical_name_systematic        ?
_chemical_formula_moiety         'C16 H25 N2 O8 P'
_chemical_formula_sum            'C16 H25 N2 O8 P'
_chemical_formula_weight         404.35
_chemical_absolute_configuration ad
_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 0.0181 0.0091 '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 0.0311 0.0180 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
O O 0.0492 0.0322 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
P P 0.2955 0.4335 '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           18
_space_group_name_H-M_alt        'P 21 21 2'
_space_group_name_Hall           'P 2 2ab'
loop_
_space_group_symop_operation_xyz
'x, y, z'
'-x, -y, z'
'x+1/2, -y+1/2, -z'
'-x+1/2, y+1/2, -z'

_cell_length_a                   11.4700(4)
_cell_length_b                   23.4314(8)
_cell_length_c                   7.3958(3)
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_volume                     1987.68(13)
_cell_formula_units_Z            4
_cell_measurement_reflns_used    9910
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      72.18
_cell_measurement_theta_min      3.77
_shelx_estimated_absorpt_T_max   0.328
_shelx_estimated_absorpt_T_min   0.245
_exptl_absorpt_coefficient_mu    1.633
_exptl_absorpt_correction_T_max  0.3859
_exptl_absorpt_correction_T_min  0.2310
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'Bruker AXScale'
_exptl_absorpt_special_details   ?
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.351
_exptl_crystal_density_meas      ?
_exptl_crystal_density_method    ?
_exptl_crystal_description       block
_exptl_crystal_F_000             856
_exptl_crystal_size_max          1.2
_exptl_crystal_size_mid          1
_exptl_crystal_size_min          0.88
_exptl_transmission_factor_max   ?
_exptl_transmission_factor_min   ?
_diffrn_reflns_av_R_equivalents  0.0468
_diffrn_reflns_av_unetI/netI     0.0307
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       28
_diffrn_reflns_limit_k_min       -28
_diffrn_reflns_limit_l_max       9
_diffrn_reflns_limit_l_min       -9
_diffrn_reflns_number            45084
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.998
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         72.555
_diffrn_reflns_theta_min         3.773
_diffrn_ambient_temperature      298(2)
_diffrn_detector_area_resol_mean ?
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device_type  'Bruker APEX II area detector'
_diffrn_measurement_method       'φ and ω scans'
_diffrn_radiation_monochromator  'multi-layer optics'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_source                   'Incoatec IMuS microfocus Cu tube'
_diffrn_special_details          ?
_diffrn_standards_number         0
_reflns_Friedel_coverage         0.730
_reflns_Friedel_fraction_full    0.999
_reflns_Friedel_fraction_max     0.997
_reflns_number_gt                3806
_reflns_number_total             3941
_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       'Bruker Apex3 V.2018.1-0/SAINT V8.38A'
_computing_data_collection       'Bruker Apex3 V.2018.1-0'
_computing_data_reduction        'Bruker Apex3 V.2018.1-0/SAINT V8.38A'
_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    ?
_refine_diff_density_max         0.345
_refine_diff_density_min         -0.417
_refine_diff_density_rms         0.076
_refine_ls_abs_structure_details 
;
 Flack x determined using 1543 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.029(10)
_refine_ls_extinction_coef       0.022(2)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2017/1 (Sheldrick 2017)'
_refine_ls_goodness_of_fit_ref   1.052
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     270
_refine_ls_number_reflns         3941
_refine_ls_number_restraints     3
_refine_ls_R_factor_all          0.0632
_refine_ls_R_factor_gt           0.0617
_refine_ls_restrained_S_all      1.052
_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/[σ²(Fo²)+(0.0981P)²+0.7138P] where P=(Fo²+2Fc²)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1638
_refine_ls_wR_factor_ref         0.1661
_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 C(H,H,H,H) groups
2. Restrained distances
 O5-H5
 0.93 with sigma of 0.02
 P1-O2 \\sim P1-O3
 with sigma of 0.02
 O2-C12 \\sim O3-C14
 with sigma of 0.02
3. Others
 Fixed Sof: C14(0.5) H14A(0.5) H14B(0.5) C14'(0.5) H14C(0.5) H14D(0.5)
 C15(0.5) H15A(0.5) H15B(0.5) H15C(0.5) C15'(0.5) H15D(0.5) H15E(0.5) H15F(0.5)
4.a Ternary CH refined with riding coordinates:
 C1(H1), C4(H4), C7(H7), C6(H6), C3(H3), C5(H5A)
4.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C12(H12A,H12B), C14(H14A,H14B), C14'(H14C,H14D)
4.c Me refined with riding coordinates:
 C13(H13A,H13B,H13C), C15(H15A,H15B,H15C), C15'(H15D,H15E,H15F)
4.d Aromatic/amide H refined with riding coordinates:
 C8(H8), C9(H9)
4.e Idealised Me refined as rotating group:
 C16(H16A,H16B,H16C)
;
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
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
P1 P 0.58275(12) 0.87825(8) 0.8422(2) 0.0961(6) Uani 1 1 d D . . . .
O4 O 0.9111(2) 0.89658(11) 0.5618(3) 0.0508(6) Uani 1 1 d . . . . .
O8 O 1.2355(2) 0.91869(11) 0.5842(5) 0.0660(8) Uani 1 1 d . . . . .
O7 O 1.3084(3) 0.73005(13) 0.6643(5) 0.0710(8) Uani 1 1 d . . . . .
O6 O 1.0449(3) 0.92978(15) 0.1505(4) 0.0702(8) Uani 1 1 d . . . . .
O1 O 0.4993(3) 0.84834(17) 0.7237(6) 0.0872(11) Uani 1 1 d . . . . .
N2 N 1.2705(3) 0.82422(14) 0.6213(5) 0.0504(7) Uani 1 1 d . . . . .
N1 N 1.0914(2) 0.85546(12) 0.5123(4) 0.0455(7) Uani 1 1 d . . . . .
C11 C 1.2023(3) 0.86971(14) 0.5730(5) 0.0449(7) Uani 1 1 d . . . . .
C10 C 1.2387(3) 0.76688(16) 0.6206(6) 0.0519(8) Uani 1 1 d . . . . .
C8 C 1.0531(3) 0.79983(15) 0.5133(6) 0.0541(9) Uani 1 1 d . . . . .
H8 H 0.977599 0.792023 0.474719 0.065 Uiso 1 1 calc R . . . .
O5 O 0.8207(3) 0.96634(15) 0.1567(5) 0.0809(10) Uani 1 1 d D . . . .
C1 C 0.6680(3) 0.9273(2) 0.7215(8) 0.0770(15) Uani 1 1 d . . . . .
H1 H 0.721986 0.950637 0.792691 0.092 Uiso 1 1 calc R . . . .
C4 C 0.8237(3) 0.92948(15) 0.4690(6) 0.0525(8) Uani 1 1 d . . . . .
H4 H 0.835405 0.970093 0.494979 0.063 Uiso 1 1 calc R . . . .
C7 C 1.0127(3) 0.90007(14) 0.4539(4) 0.0451(7) Uani 1 1 d . . . . .
H7 H 1.049796 0.937284 0.472436 0.054 Uiso 1 1 calc R . . . .
C6 C 0.9700(3) 0.89577(18) 0.2585(5) 0.0539(8) Uani 1 1 d . . . . .
H6 H 0.970973 0.856017 0.217334 0.065 Uiso 1 1 calc R . . . .
C3 C 0.7068(3) 0.91160(16) 0.5358(6) 0.0555(9) Uani 1 1 d . . . . .
H3 H 0.679663 0.874388 0.492350 0.067 Uiso 1 1 calc R . . . .
C9 C 1.1203(3) 0.75673(16) 0.5676(7) 0.0607(10) Uani 1 1 d . . . . .
H9 H 1.090295 0.719876 0.571011 0.073 Uiso 1 1 calc R . . . .
C5 C 0.8437(4) 0.91861(17) 0.2665(6) 0.0583(9) Uani 1 1 d . . . . .
H5A H 0.791405 0.887754 0.228919 0.070 Uiso 1 1 calc R . . . .
C2 C 0.6148(4) 0.9551(2) 0.5603(13) 0.103(2) Uani 1 1 d . . . . .
H2A H 0.535575 0.944641 0.528865 0.123 Uiso 1 1 calc R . . . .
H2B H 0.635007 0.994581 0.536488 0.123 Uiso 1 1 calc R . . . .
O3 O 0.6677(5) 0.8398(3) 0.9540(9) 0.143(2) Uani 1 1 d D . . . .
O2 O 0.5277(5) 0.9137(4) 0.9975(10) 0.210(5) Uani 1 1 d D . . . .
C16 C 1.0388(8) 0.9155(3) -0.0382(7) 0.110(2) Uani 1 1 d . . . . .
H16A H 1.093287 0.938436 -0.104502 0.165 Uiso 1 1 calc GR . . . .
H16B H 0.961317 0.922537 -0.082062 0.165 Uiso 1 1 calc GR . . . .
H16C H 1.057544 0.875855 -0.054038 0.165 Uiso 1 1 calc GR . . . .
C12 C 0.4177(13) 0.9211(7) 1.047(2) 0.232(8) Uani 1 1 d D . . . .
H12A H 0.409402 0.961862 1.066347 0.279 Uiso 1 1 calc R . . . .
H12B H 0.372002 0.912482 0.939757 0.279 Uiso 1 1 calc R . . . .
C13 C 0.3695(16) 0.9003(11) 1.162(2) 0.283(11) Uani 1 1 d . . . . .
H13A H 0.290582 0.913980 1.165000 0.425 Uiso 1 1 calc R . . . .
H13B H 0.369524 0.859690 1.146126 0.425 Uiso 1 1 calc R . . . .
H13C H 0.407376 0.909666 1.274245 0.425 Uiso 1 1 calc R . . . .
C14 C 0.695(3) 0.7869(9) 0.908(4) 0.144(11) Uani 0.5 1 d D . P A 1
H14A H 0.660825 0.784253 0.788471 0.173 Uiso 0.5 1 calc R . P A 1
H14B H 0.643251 0.765050 0.984998 0.173 Uiso 0.5 1 calc R . P A 1
C14' C 0.760(5) 0.8001(13) 0.863(4) 0.25(3) Uani 0.5 1 d . . P A 2
H14C H 0.833308 0.796019 0.928349 0.296 Uiso 0.5 1 calc R . P A 2
H14D H 0.771663 0.805622 0.734556 0.296 Uiso 0.5 1 calc R . P A 2
C15 C 0.795(4) 0.748(2) 0.891(5) 0.25(2) Uani 0.5 1 d . . P A 1
H15A H 0.767821 0.711513 0.849712 0.382 Uiso 0.5 1 calc R . P A 1
H15B H 0.849450 0.763390 0.806234 0.382 Uiso 0.5 1 calc R . P A 1
H15C H 0.831500 0.743776 1.006968 0.382 Uiso 0.5 1 calc R . P A 1
C15' C 0.659(3) 0.7553(13) 0.919(3) 0.165(10) Uani 0.5 1 d . . P A 2
H15D H 0.681259 0.717483 0.882753 0.247 Uiso 0.5 1 calc R . P A 2
H15E H 0.647322 0.756235 1.047336 0.247 Uiso 0.5 1 calc R . P A 2
H15F H 0.587445 0.765562 0.859097 0.247 Uiso 0.5 1 calc R . P A 2
H2 H 1.358(10) 0.829(4) 0.633(18) 0.198 Uiso 1 1 d R . . . .
H5 H 0.886(8) 0.987(5) 0.203(18) 0.247 Uiso 1 1 d DR . . . .


_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
P1 O1 1.475(4) . ?
P1 C1 1.753(6) . ?
P1 O3 1.563(7) . ?
P1 O2 1.552(6) . ?
O4 C4 1.439(4) . ?
O4 C7 1.415(4) . ?
O8 C11 1.212(4) . ?
O7 C10 1.220(5) . ?
O6 C6 1.418(5) . ?
O6 C16 1.437(6) . ?
N2 C11 1.369(5) . ?
N2 C10 1.392(5) . ?
N1 C11 1.390(4) . ?
N1 C8 1.375(5) . ?
N1 C7 1.447(4) . ?
C10 C9 1.433(5) . ?
C8 C9 1.333(6) . ?
O5 C5 1.407(5) . ?
C1 C3 1.489(7) . ?
C1 C2 1.489(10) . ?
C4 C3 1.489(5) . ?
C4 C5 1.536(6) . ?
C7 C6 1.529(5) . ?
C6 C5 1.545(6) . ?
C3 C2 1.478(5) . ?
O3 C14 1.322(19) . ?
O3 C14' 1.56(5) . ?
O2 C12 1.325(13) . ?
C12 C13 1.129(19) . ?
C14 C15 1.46(4) . ?
C14' C15' 1.62(4) . ?

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
O1 P1 C1 111.8(3) . . ?
O1 P1 O3 116.4(3) . . ?
O1 P1 O2 115.5(3) . . ?
O3 P1 C1 107.4(3) . . ?
O2 P1 C1 104.7(4) . . ?
O2 P1 O3 99.8(5) . . ?
C7 O4 C4 105.9(3) . . ?
C6 O6 C16 112.7(4) . . ?
C11 N2 C10 126.9(3) . . ?
C11 N1 C7 119.6(3) . . ?
C8 N1 C11 121.2(3) . . ?
C8 N1 C7 119.1(3) . . ?
O8 C11 N2 122.7(3) . . ?
O8 C11 N1 122.5(3) . . ?
N2 C11 N1 114.8(3) . . ?
O7 C10 N2 120.7(3) . . ?
O7 C10 C9 125.2(4) . . ?
N2 C10 C9 114.2(3) . . ?
C9 C8 N1 122.3(3) . . ?
C3 C1 P1 118.3(3) . . ?
C2 C1 P1 117.8(3) . . ?
C2 C1 C3 59.5(4) . . ?
O4 C4 C3 108.6(3) . . ?
O4 C4 C5 105.8(3) . . ?
C3 C4 C5 114.3(3) . . ?
O4 C7 N1 107.7(3) . . ?
O4 C7 C6 105.4(3) . . ?
N1 C7 C6 115.8(3) . . ?
O6 C6 C7 107.5(3) . . ?
O6 C6 C5 113.3(3) . . ?
C7 C6 C5 103.9(3) . . ?
C1 C3 C4 120.4(3) . . ?
C2 C3 C1 60.2(4) . . ?
C2 C3 C4 119.3(4) . . ?
C8 C9 C10 120.3(3) . . ?
O5 C5 C4 113.8(3) . . ?
O5 C5 C6 115.4(4) . . ?
C4 C5 C6 103.6(3) . . ?
C3 C2 C1 60.3(3) . . ?
P1 O3 C14' 122.7(15) . . ?
C14 O3 P1 123.5(9) . . ?
C12 O2 P1 131.4(8) . . ?
C13 C12 O2 128(2) . . ?
O3 C14 C15 142(4) . . ?
O3 C14' C15' 78(3) . . ?

_olex2_submission_special_instructions 'No special instructions were received'
