# Electronic Supplementary Material (ESI) for RSC Advances.
# This journal is © The Royal Society of Chemistry 2019

####################################################################### 
# 
# 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_NIH18
_database_code_depnum_ccdc_archive 'CCDC 1897285'
loop_
_audit_author_name
_audit_author_address
'Curtis Moore'
;Ohio State University
United States of America
;
_audit_update_record             
;
2019-02-14 deposited with the CCDC.	2019-11-27 downloaded from the CCDC.
;
_audit_creation_date             2016-08-15
_audit_creation_method           
;
Olex2 1.2-beta
(compiled 2016.07.26 svn.r3321 for OlexSys, GUI svn.r5206)
;
_chemical_name_common            ?
_chemical_name_systematic        
'benzyl ((2S,3R)-3-hydroxy-4-methyl-1-oxo-1-(phenylamino)pentan-2-yl)(methyl)carbamate'
_chemical_formula_moiety         'C21 H26 N2 O4'
_chemical_formula_sum            'C21 H26 N2 O4'
_chemical_formula_weight         370.44
_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'

_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           19
_space_group_name_H-M_alt        'P 21 21 21'
_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'

_cell_length_a                   10.2972(4)
_cell_length_b                   11.7362(4)
_cell_length_c                   16.2355(6)
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_volume                     1962.06(12)
_cell_formula_units_Z            4
_cell_measurement_reflns_used    9718
_cell_measurement_temperature    125
_cell_measurement_theta_max      68.278
_cell_measurement_theta_min      4.649
_shelx_estimated_absorpt_T_max   0.965
_shelx_estimated_absorpt_T_min   0.862
_exptl_absorpt_coefficient_mu    0.707
_exptl_absorpt_correction_T_max  0.3201
_exptl_absorpt_correction_T_min  0.2018
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   
;
SADABS-2014/5 (Bruker,2014/5) was used for absorption correction.
wR2(int) was 0.1090 before and 0.0698 after correction.
The Ratio of minimum to maximum transmission is 0.6304.
The λ/2 correction factor is Not present.
;
_exptl_absorpt_special_details   ?
_exptl_crystal_colour            Colorless
_exptl_crystal_colour_primary    Colorless
_exptl_crystal_density_diffrn    1.254
_exptl_crystal_density_meas      ?
_exptl_crystal_density_method    ?
_exptl_crystal_description       Rod
_exptl_crystal_F_000             792
_exptl_crystal_size_max          0.217
_exptl_crystal_size_mid          0.053
_exptl_crystal_size_min          0.051
_exptl_transmission_factor_max   ?
_exptl_transmission_factor_min   ?
_diffrn_reflns_av_R_equivalents  0.0549
_diffrn_reflns_av_unetI/netI     0.0205
_diffrn_reflns_Laue_measured_fraction_full 0.984
_diffrn_reflns_Laue_measured_fraction_max 0.983
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            33864
_diffrn_reflns_point_group_measured_fraction_full 0.985
_diffrn_reflns_point_group_measured_fraction_max 0.984
_diffrn_reflns_theta_full        68.000
_diffrn_reflns_theta_max         68.273
_diffrn_reflns_theta_min         4.649
_diffrn_ambient_temperature      125
_diffrn_detector                 'Bruker Platinum135 CCD'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            'CCD Area Detector'
_diffrn_measured_fraction_theta_full 0.984
_diffrn_measured_fraction_theta_max 0.983
_diffrn_measurement_device       'Fixed Chi Three-Circle Diffractometer'
_diffrn_measurement_device_type  'Bruker D8 Platinum135'
_diffrn_measurement_method       'ω and φ scans'
_diffrn_radiation_monochromator  'Double Bounce Multilayer Mirrors'
_diffrn_radiation_probe          X-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_source                   'Micro Focus Rotating Anode'
_diffrn_source_type              'Rigaku MicroMax-007HF'
_diffrn_special_details          ?
_diffrn_standards_number         0
_reflns_Friedel_coverage         0.748
_reflns_Friedel_fraction_full    0.987
_reflns_Friedel_fraction_max     0.985
_reflns_number_gt                3501
_reflns_number_total             3547
_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       'SAINT v8.37A (Bruker, 2016)'
_computing_data_collection       'APEX3 v2016.1-0 (Bruker, 2016)'
_computing_data_reduction        'SAINT v8.37A (Bruker, 2016)'
_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         0.113
_refine_diff_density_min         -0.179
_refine_diff_density_rms         0.033
_refine_ls_abs_structure_details 
;
 Flack x determined using 1488 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.05(3)
_refine_ls_extinction_coef       .
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.086
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     255
_refine_ls_number_reflns         3547
_refine_ls_number_restraints     2
_refine_ls_R_factor_all          0.0256
_refine_ls_R_factor_gt           0.0252
_refine_ls_restrained_S_all      1.088
_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)+(0.0283P)²+0.3380P] where P=(Fo²+2Fc²)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0636
_refine_ls_wR_factor_ref         0.0639
_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
2. Restrained distances
 O2-H2 = N1-H1
 0.95 with sigma of 0.02
3.a Ternary CH refined with riding coordinates:
 C2(H2A), C3(H3), C4(H4)
3.b Secondary CH2 refined with riding coordinates:
 C15(H15A,H15B)
3.c Aromatic/amide H refined with riding coordinates:
 C10(H10), C11(H11), C12(H12), C13(H13), C14(H14), C17(H17), C18(H18),
 C19(H19), C20(H20), C21(H21)
3.d Idealised Me refined as rotating group:
 C5(H5A,H5B,H5C), C6(H6A,H6B,H6C), C7(H7A,H7B,H7C)
;
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_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
O1 O 0.52575(11) 0.44092(10) 0.45516(7) 0.0268(3) Uani 1 1 d . . . . .
O2 O 0.33401(12) 0.72211(10) 0.56071(8) 0.0266(3) Uani 1 1 d D . . . .
H2 H 0.2545(19) 0.706(2) 0.5790(14) 0.044(6) Uiso 1 1 d D . . . .
O3 O 0.58693(11) 0.82639(10) 0.39247(7) 0.0267(3) Uani 1 1 d . . . . .
O4 O 0.41986(12) 0.80198(10) 0.30381(7) 0.0272(3) Uani 1 1 d . . . . .
N1 N 0.71490(13) 0.54222(12) 0.46600(8) 0.0211(3) Uani 1 1 d D . . . .
H1 H 0.748(2) 0.6132(15) 0.4723(12) 0.030(5) Uiso 1 1 d D . . . .
N2 N 0.44562(13) 0.67744(11) 0.40656(8) 0.0219(3) Uani 1 1 d . . . . .
C1 C 0.58406(16) 0.53063(14) 0.46707(9) 0.0199(3) Uani 1 1 d . . . . .
C2 C 0.50732(15) 0.64047(13) 0.48367(10) 0.0202(3) Uani 1 1 d . . . . .
H2A H 0.5690 0.7010 0.5023 0.024 Uiso 1 1 calc R . . . .
C3 C 0.40726(16) 0.61931(13) 0.55203(10) 0.0220(3) Uani 1 1 d . . . . .
H3 H 0.3474 0.5571 0.5340 0.026 Uiso 1 1 calc R . . . .
C4 C 0.47260(17) 0.58322(15) 0.63325(10) 0.0257(4) Uani 1 1 d . . . . .
H4 H 0.5261 0.5140 0.6216 0.031 Uiso 1 1 calc R . . . .
C5 C 0.36942(19) 0.54991(16) 0.69671(11) 0.0319(4) Uani 1 1 d . . . . .
H5A H 0.3160 0.6165 0.7099 0.048 Uiso 1 1 calc GR . . . .
H5B H 0.4120 0.5223 0.7469 0.048 Uiso 1 1 calc GR . . . .
H5C H 0.3143 0.4896 0.6740 0.048 Uiso 1 1 calc GR . . . .
C6 C 0.56356(19) 0.67480(17) 0.66744(11) 0.0346(4) Uani 1 1 d . . . . .
H6A H 0.6424 0.6783 0.6337 0.052 Uiso 1 1 calc GR . . . .
H6B H 0.5869 0.6559 0.7243 0.052 Uiso 1 1 calc GR . . . .
H6C H 0.5197 0.7489 0.6662 0.052 Uiso 1 1 calc GR . . . .
C7 C 0.33492(17) 0.61340(15) 0.37404(11) 0.0291(4) Uani 1 1 d . . . . .
H7A H 0.2558 0.6358 0.4035 0.044 Uiso 1 1 calc GR . . . .
H7B H 0.3501 0.5316 0.3817 0.044 Uiso 1 1 calc GR . . . .
H7C H 0.3247 0.6299 0.3152 0.044 Uiso 1 1 calc GR . . . .
C8 C 0.49182(15) 0.77233(13) 0.36957(10) 0.0209(3) Uani 1 1 d . . . . .
C9 C 0.80877(15) 0.45620(14) 0.45013(9) 0.0210(3) Uani 1 1 d . . . . .
C10 C 0.77682(17) 0.34179(15) 0.43871(11) 0.0262(4) Uani 1 1 d . . . . .
H10 H 0.6888 0.3178 0.4406 0.031 Uiso 1 1 calc R . . . .
C11 C 0.87559(18) 0.26311(15) 0.42454(11) 0.0302(4) Uani 1 1 d . . . . .
H11 H 0.8541 0.1851 0.4167 0.036 Uiso 1 1 calc R . . . .
C12 C 1.00400(18) 0.29624(16) 0.42166(11) 0.0323(4) Uani 1 1 d . . . . .
H12 H 1.0704 0.2417 0.4120 0.039 Uiso 1 1 calc R . . . .
C13 C 1.03499(18) 0.41015(16) 0.43298(12) 0.0327(4) Uani 1 1 d . . . . .
H13 H 1.1232 0.4337 0.4310 0.039 Uiso 1 1 calc R . . . .
C14 C 0.93796(17) 0.49020(15) 0.44716(11) 0.0274(4) Uani 1 1 d . . . . .
H14 H 0.9600 0.5681 0.4548 0.033 Uiso 1 1 calc R . . . .
C15 C 0.46854(19) 0.89784(15) 0.25532(10) 0.0299(4) Uani 1 1 d . . . . .
H15A H 0.4460 0.8861 0.1967 0.036 Uiso 1 1 calc R . . . .
H15B H 0.5644 0.9008 0.2597 0.036 Uiso 1 1 calc R . . . .
C16 C 0.41235(17) 1.00921(14) 0.28415(10) 0.0239(3) Uani 1 1 d . . . . .
C17 C 0.29319(18) 1.04582(16) 0.25407(11) 0.0298(4) Uani 1 1 d . . . . .
H17 H 0.2466 0.9996 0.2162 0.036 Uiso 1 1 calc R . . . .
C18 C 0.24186(18) 1.14927(16) 0.27898(12) 0.0333(4) Uani 1 1 d . . . . .
H18 H 0.1601 1.1737 0.2584 0.040 Uiso 1 1 calc R . . . .
C19 C 0.30966(17) 1.21706(15) 0.33396(11) 0.0306(4) Uani 1 1 d . . . . .
H19 H 0.2748 1.2884 0.3506 0.037 Uiso 1 1 calc R . . . .
C20 C 0.42780(18) 1.18121(15) 0.36467(11) 0.0284(4) Uani 1 1 d . . . . .
H20 H 0.4739 1.2275 0.4028 0.034 Uiso 1 1 calc R . . . .
C21 C 0.47909(17) 1.07752(15) 0.33985(10) 0.0261(4) Uani 1 1 d . . . . .
H21 H 0.5604 1.0530 0.3610 0.031 Uiso 1 1 calc R . . . .


_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
O1 C1 1.227(2) . ?
O2 H2 0.890(19) . ?
O2 C3 1.4299(18) . ?
O3 C8 1.225(2) . ?
O4 C8 1.345(2) . ?
O4 C15 1.462(2) . ?
N1 H1 0.906(17) . ?
N1 C1 1.354(2) . ?
N1 C9 1.421(2) . ?
N2 C2 1.469(2) . ?
N2 C7 1.464(2) . ?
N2 C8 1.352(2) . ?
C1 C2 1.536(2) . ?
C2 H2A 1.0000 . ?
C2 C3 1.535(2) . ?
C3 H3 1.0000 . ?
C3 C4 1.540(2) . ?
C4 H4 1.0000 . ?
C4 C5 1.531(2) . ?
C4 C6 1.530(3) . ?
C5 H5A 0.9800 . ?
C5 H5B 0.9800 . ?
C5 H5C 0.9800 . ?
C6 H6A 0.9800 . ?
C6 H6B 0.9800 . ?
C6 H6C 0.9800 . ?
C7 H7A 0.9800 . ?
C7 H7B 0.9800 . ?
C7 H7C 0.9800 . ?
C9 C10 1.395(2) . ?
C9 C14 1.390(2) . ?
C10 H10 0.9500 . ?
C10 C11 1.393(2) . ?
C11 H11 0.9500 . ?
C11 C12 1.379(3) . ?
C12 H12 0.9500 . ?
C12 C13 1.387(3) . ?
C13 H13 0.9500 . ?
C13 C14 1.391(2) . ?
C14 H14 0.9500 . ?
C15 H15A 0.9900 . ?
C15 H15B 0.9900 . ?
C15 C16 1.504(2) . ?
C16 C17 1.389(3) . ?
C16 C21 1.390(2) . ?
C17 H17 0.9500 . ?
C17 C18 1.385(3) . ?
C18 H18 0.9500 . ?
C18 C19 1.385(3) . ?
C19 H19 0.9500 . ?
C19 C20 1.380(3) . ?
C20 H20 0.9500 . ?
C20 C21 1.387(3) . ?
C21 H21 0.9500 . ?

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
C3 O2 H2 110.1(15) . . ?
C8 O4 C15 115.95(13) . . ?
C1 N1 H1 117.6(14) . . ?
C1 N1 C9 127.42(14) . . ?
C9 N1 H1 114.8(14) . . ?
C7 N2 C2 119.49(13) . . ?
C8 N2 C2 118.01(13) . . ?
C8 N2 C7 122.46(14) . . ?
O1 C1 N1 124.81(15) . . ?
O1 C1 C2 119.73(14) . . ?
N1 C1 C2 115.46(14) . . ?
N2 C2 C1 108.72(12) . . ?
N2 C2 H2A 108.8 . . ?
N2 C2 C3 111.94(13) . . ?
C1 C2 H2A 108.8 . . ?
C3 C2 C1 109.66(12) . . ?
C3 C2 H2A 108.8 . . ?
O2 C3 C2 106.79(12) . . ?
O2 C3 H3 108.7 . . ?
O2 C3 C4 112.23(13) . . ?
C2 C3 H3 108.7 . . ?
C2 C3 C4 111.75(13) . . ?
C4 C3 H3 108.7 . . ?
C3 C4 H4 107.6 . . ?
C5 C4 C3 110.08(14) . . ?
C5 C4 H4 107.6 . . ?
C6 C4 C3 112.64(14) . . ?
C6 C4 H4 107.6 . . ?
C6 C4 C5 111.11(15) . . ?
C4 C5 H5A 109.5 . . ?
C4 C5 H5B 109.5 . . ?
C4 C5 H5C 109.5 . . ?
H5A C5 H5B 109.5 . . ?
H5A C5 H5C 109.5 . . ?
H5B C5 H5C 109.5 . . ?
C4 C6 H6A 109.5 . . ?
C4 C6 H6B 109.5 . . ?
C4 C6 H6C 109.5 . . ?
H6A C6 H6B 109.5 . . ?
H6A C6 H6C 109.5 . . ?
H6B C6 H6C 109.5 . . ?
N2 C7 H7A 109.5 . . ?
N2 C7 H7B 109.5 . . ?
N2 C7 H7C 109.5 . . ?
H7A C7 H7B 109.5 . . ?
H7A C7 H7C 109.5 . . ?
H7B C7 H7C 109.5 . . ?
O3 C8 O4 123.18(15) . . ?
O3 C8 N2 124.98(15) . . ?
O4 C8 N2 111.83(14) . . ?
C10 C9 N1 123.19(15) . . ?
C14 C9 N1 116.96(15) . . ?
C14 C9 C10 119.84(16) . . ?
C9 C10 H10 120.4 . . ?
C11 C10 C9 119.20(16) . . ?
C11 C10 H10 120.4 . . ?
C10 C11 H11 119.4 . . ?
C12 C11 C10 121.25(17) . . ?
C12 C11 H11 119.4 . . ?
C11 C12 H12 120.4 . . ?
C11 C12 C13 119.21(16) . . ?
C13 C12 H12 120.4 . . ?
C12 C13 H13 119.7 . . ?
C12 C13 C14 120.53(17) . . ?
C14 C13 H13 119.7 . . ?
C9 C14 C13 119.96(17) . . ?
C9 C14 H14 120.0 . . ?
C13 C14 H14 120.0 . . ?
O4 C15 H15A 109.3 . . ?
O4 C15 H15B 109.3 . . ?
O4 C15 C16 111.68(13) . . ?
H15A C15 H15B 107.9 . . ?
C16 C15 H15A 109.3 . . ?
C16 C15 H15B 109.3 . . ?
C17 C16 C15 119.95(16) . . ?
C17 C16 C21 119.15(16) . . ?
C21 C16 C15 120.89(17) . . ?
C16 C17 H17 119.8 . . ?
C18 C17 C16 120.39(17) . . ?
C18 C17 H17 119.8 . . ?
C17 C18 H18 120.0 . . ?
C17 C18 C19 119.98(17) . . ?
C19 C18 H18 120.0 . . ?
C18 C19 H19 119.9 . . ?
C20 C19 C18 120.14(17) . . ?
C20 C19 H19 119.9 . . ?
C19 C20 H20 120.1 . . ?
C19 C20 C21 119.88(17) . . ?
C21 C20 H20 120.1 . . ?
C16 C21 H21 119.8 . . ?
C20 C21 C16 120.46(17) . . ?
C20 C21 H21 119.8 . . ?

loop_
_geom_hbond_atom_site_label_D
_geom_hbond_atom_site_label_H
_geom_hbond_atom_site_label_A
_geom_hbond_distance_DH
_geom_hbond_distance_HA
_geom_hbond_distance_DA
_geom_hbond_angle_DHA
_geom_hbond_site_symmetry_A
O2 H2 O3 0.890(19) 1.828(19) 2.7157(17) 175(2) 4_466
N1 H1 O2 0.906(17) 2.193(18) 3.0566(18) 159.2(18) 4_566

_shelx_SHELXL_version_number     2014/7
_olex2_submission_special_instructions 'No special instructions were received'
_exptl_crystal_recrystallization_method 
'Re-crystallisation from solvent: Diethyl ether and Hexane'
