# Supplementary Material (ESI) for Organic & Biomolecular Chemistry
# This journal is (c) The Royal Society of Chemistry 2010

data_989GuillotICMMO
_publ_requested_journal          Org.Biomol.Chem.
_publ_contact_author_name        'Val\'erie Alezra'
_publ_contact_author_address     
;Univ. Paris-Sud, 
Institut de Chimie Mol\'eculaire et des Mat\'eriaux d'Orsay, 
UMR 8182, B\^atiment 410, 
CNRS,
Orsay, 91405
FRANCE.
;
_publ_contact_author_email       valerie.alezra@u-psud.fr
_publ_contact_author_phone       '+33 1 69 15 76 50'
_publ_contact_author_fax         '+33 1 69 15 46 79'
loop_
_publ_author_name
_publ_author_address
'Bouill\`ere, Francelin'
;Univ. Paris-Sud, 
Institut de Chimie Mol\'eculaire et des Mat\'eriaux d'Orsay, 
UMR 8182, B\^atiment 410, 
CNRS,
Orsay, 91405
FRANCE.
;
'Guillot, R\'egis'
;Univ. Paris-Sud, 
Institut de Chimie Mol\'eculaire et des Mat\'eriaux d'Orsay, 
UMR 8182, B\^atiment 410, 
CNRS,
Orsay, 91405
FRANCE.
;
'Alezra, Val\'erie '
;Univ. Paris-Sud, 
Institut de Chimie Mol\'eculaire et des Mat\'eriaux d'Orsay, 
UMR 8182, B\^atiment 410, 
CNRS,
Orsay, 91405
FRANCE.
;
'Kouklovsky, Cyrille'
;Univ. Paris-Sud, 
Institut de Chimie Mol\'eculaire et des Mat\'eriaux d'Orsay, 
UMR 8182, B\^atiment 410, 
CNRS,
Orsay, 91405
FRANCE.
;

_audit_creation_method           SHELXL-97
_chemical_name_systematic        ?
_chemical_name_common            ?
_chemical_formula_moiety         'C21 H32 N2 O6'
_chemical_formula_sum            'C21 H32 N2 O6'
_chemical_melting_point          ?

_exptl_crystal_description       ?
_exptl_crystal_colour            ?

_diffrn_ambient_temperature      100(1)
_chemical_formula_weight         408.49

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 0.0000 '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 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
O O 0.0106 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'

_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_H-M   'P 21'
_symmetry_int_tables_number      4
_chemical_absolute_configuration syn

loop_
_symmetry_equiv_pos_as_xyz
'x, y, z'
'-x, y+1/2, -z'

_cell_length_a                   5.1216(3)
_cell_length_b                   10.4652(6)
_cell_length_c                   21.3646(14)
_cell_angle_alpha                90.00
_cell_angle_beta                 95.373(2)
_cell_angle_gamma                90.00
_cell_volume                     1140.08(12)
_cell_formula_units_Z            2
_cell_measurement_temperature    100(1)
_cell_measurement_reflns_used    8501
_cell_measurement_theta_min      2.73
_cell_measurement_theta_max      22.92
_exptl_crystal_size_max          0.180
_exptl_crystal_size_mid          0.060
_exptl_crystal_size_min          0.020
_exptl_crystal_density_meas      ?
_exptl_crystal_density_diffrn    1.190
_exptl_crystal_density_method    'not measured'
_exptl_crystal_F_000             440
_exptl_absorpt_coefficient_mu    0.087
_exptl_absorpt_correction_type   psi-scan
_exptl_absorpt_correction_T_min  0.991
_exptl_absorpt_correction_T_max  0.999
_exptl_absorpt_process_details   SADABS

_exptl_special_details           
;
 ?
;
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_source                   'fine-focus sealed tube'
_diffrn_source_type              'kappa X8 APEX II Bruker ICMMO'
_diffrn_radiation_monochromator  graphite
_diffrn_measurement_device_type  'CCD area detector'
_diffrn_measurement_method       'phi and omega scans'
_diffrn_detector_area_resol_mean ?
_diffrn_standards_number         ?
_diffrn_standards_interval_count ?
_diffrn_standards_interval_time  ?
_diffrn_standards_decay_%        ?
_diffrn_reflns_number            21351
_diffrn_reflns_av_R_equivalents  0.0428
_diffrn_reflns_av_sigmaI/netI    0.0214
_diffrn_reflns_limit_h_min       -5
_diffrn_reflns_limit_h_max       5
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_limit_l_max       23
_diffrn_reflns_theta_min         2.17
_diffrn_reflns_theta_max         23.30
_reflns_number_total             1751
_reflns_number_gt                1609
_reflns_threshold_expression     >2sigma(I)

_computing_data_collection       ?
_computing_cell_refinement       ?
_computing_data_reduction        ?
_computing_structure_solution    ?
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_molecular_graphics    ?
_computing_publication_material  ?

_refine_special_details          
;
 Refinement of F^2^ against ALL reflections.  The weighted R-factor wR and
 goodness of fit S are based on F^2^, conventional R-factors R are based
 on F, with F set to zero for negative F^2^. The threshold expression of
 F^2^ > 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is
 not relevant to the choice of reflections for refinement.  R-factors based
 on F^2^ are statistically about twice as large as those based on F, and R-
 factors based on ALL data will be even larger.
;

_refine_ls_structure_factor_coef Fsqd
_refine_ls_matrix_type           full
_refine_ls_weighting_scheme      calc
_refine_ls_weighting_details     
'calc w=1/[\s^2^(Fo^2^)+(0.1967P)^2^+3.8309P] where P=(Fo^2^+2Fc^2^)/3'
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_atom_sites_solution_hydrogens   geom
_refine_ls_hydrogen_treatment    constr
_refine_ls_extinction_method     SHELXL
_refine_ls_extinction_coef       0.019(13)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   10(10)
_refine_ls_number_reflns         1751
_refine_ls_number_parameters     261
_refine_ls_number_restraints     115
_refine_ls_R_factor_all          0.1255
_refine_ls_R_factor_gt           0.1177
_refine_ls_wR_factor_ref         0.3263
_refine_ls_wR_factor_gt          0.3160
_refine_ls_goodness_of_fit_ref   1.061
_refine_ls_restrained_S_all      1.066
_refine_ls_shift/su_max          0.051
_refine_ls_shift/su_mean         0.018

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_symmetry_multiplicity
_atom_site_calc_flag
_atom_site_refinement_flags
_atom_site_disorder_assembly
_atom_site_disorder_group
C5A C 0.647(5) 0.547(2) 0.7709(11) 0.069(2) Uani 0.50 1 d PDU A 1
H5A1 H 0.5161 0.5960 0.7894 0.103 Uiso 0.50 1 calc PR A 1
H5A2 H 0.7069 0.4791 0.7990 0.103 Uiso 0.50 1 calc PR A 1
H5A3 H 0.5738 0.5113 0.7318 0.103 Uiso 0.50 1 calc PR A 1
C18A C 0.934(6) 1.221(3) 0.7902(12) 0.066(8) Uani 0.50 1 d P B 1
H18A H 0.8554 1.1561 0.8139 0.098 Uiso 0.50 1 calc PR B 1
H18B H 0.8641 1.3032 0.8004 0.098 Uiso 0.50 1 calc PR B 1
H18C H 1.1201 1.2211 0.8004 0.098 Uiso 0.50 1 calc PR B 1
C10A C 0.878(16) 1.198(8) 0.727(8) 0.081(9) Uani 0.50 1 d PD B 1
H10A H 0.6861 1.2046 0.7206 0.097 Uiso 0.50 1 calc PR B 1
C10B C 0.821(14) 1.191(8) 0.723(9) 0.081(9) Uani 0.50 1 d PD B 2
H10B H 0.9103 1.1949 0.7661 0.097 Uiso 0.50 1 calc PR B 2
C5B C 0.409(5) 0.591(2) 0.7235(11) 0.069(2) Uani 0.50 1 d PDU A 2
H5B1 H 0.4424 0.5061 0.7091 0.103 Uiso 0.50 1 calc PR A 2
H5B2 H 0.2228 0.6048 0.7216 0.103 Uiso 0.50 1 calc PR A 2
H5B3 H 0.4841 0.6009 0.7660 0.103 Uiso 0.50 1 calc PR A 2
C18B C 0.622(5) 1.240(3) 0.7309(11) 0.062(8) Uani 0.50 1 d P B 2
H18D H 0.6523 1.3284 0.7418 0.094 Uiso 0.50 1 calc PR B 2
H18E H 0.5425 1.1980 0.7642 0.094 Uiso 0.50 1 calc PR B 2
H18F H 0.5072 1.2350 0.6928 0.094 Uiso 0.50 1 calc PR B 2
O5A O 0.874(3) 0.6314(19) 0.7595(8) 0.069(2) Uani 0.50 1 d PDU A 1
O5B O 0.529(3) 0.687(2) 0.6822(8) 0.069(2) Uani 0.50 1 d PDU A 2
C13 C 0.637(3) 0.975(3) 0.9941(5) 0.186(13) Uani 1 1 d GU . .
C15 C 0.808(3) 1.073(3) 1.0137(8) 0.236(15) Uani 1 1 d GU . .
H15 H 0.8478 1.1361 0.9855 0.283 Uiso 1 1 calc R . .
C16 C 0.921(4) 1.076(3) 1.0755(9) 0.253(15) Uani 1 1 d GU . .
H16 H 1.0353 1.1421 1.0886 0.303 Uiso 1 1 calc R . .
C19 C 0.861(4) 0.982(3) 1.1177(6) 0.246(16) Uani 1 1 d GU . .
H19 H 0.9365 0.9844 1.1590 0.295 Uiso 1 1 calc R . .
C20 C 0.690(5) 0.884(3) 1.0980(7) 0.294(17) Uani 1 1 d GU . .
H20 H 0.6501 0.8207 1.1263 0.353 Uiso 1 1 calc R . .
C23 C 0.577(4) 0.880(3) 1.0363(8) 0.270(16) Uani 1 1 d GU . .
H23 H 0.4626 0.8147 1.0231 0.324 Uiso 1 1 calc R . .
C3 C 1.303(2) 0.9519(13) 0.4810(5) 0.038(2) Uani 1 1 d . . .
H3A H 1.1932 0.8798 0.4880 0.056 Uiso 1 1 calc R . .
H3B H 1.4416 0.9572 0.5143 0.056 Uiso 1 1 calc R . .
H3C H 1.3757 0.9420 0.4416 0.056 Uiso 1 1 calc R . .
C2 C 1.1402(14) 1.0728(14) 0.4798(4) 0.0282(18) Uani 1 1 d . . .
C4 C 1.3063(17) 1.1929(13) 0.4840(4) 0.028(2) Uani 1 1 d . . .
H4A H 1.4167 1.1929 0.5229 0.042 Uiso 1 1 calc R . .
H4B H 1.1942 1.2666 0.4824 0.042 Uiso 1 1 calc R . .
H4C H 1.4132 1.1954 0.4494 0.042 Uiso 1 1 calc R . .
C1 C 0.9442(15) 1.0769(15) 0.4225(4) 0.033(2) Uani 1 1 d . . .
H1A H 0.8484 1.1558 0.4220 0.050 Uiso 1 1 calc R . .
H1B H 0.8246 1.0065 0.4238 0.050 Uiso 1 1 calc R . .
H1C H 1.0348 1.0709 0.3853 0.050 Uiso 1 1 calc R . .
O1 O 0.9697(9) 1.0705(12) 0.5317(2) 0.0287(13) Uani 1 1 d . . .
C5 C 1.0739(14) 1.0668(14) 0.5924(3) 0.0271(18) Uani 1 1 d . . .
O2 O 1.3056(10) 1.0657(13) 0.6096(3) 0.0366(15) Uani 1 1 d . . .
N1 N 0.8819(12) 1.0656(14) 0.6302(3) 0.0360(18) Uani 1 1 d . B .
H1 H 0.7221 1.0619 0.6138 0.043 Uiso 1 1 calc R . .
C6 C 0.9337(19) 1.0703(2) 0.6993(4) 0.038(2) Uani 1 1 d D . .
H6 H 1.1223 1.0556 0.7087 0.046 Uiso 1 1 calc R B 1
C8 C 0.895(2) 0.8251(13) 0.6984(5) 0.043(3) Uani 1 1 d D . .
H8A H 0.8769 0.8283 0.6528 0.051 Uiso 1 1 calc R B .
H8B H 1.0791 0.8133 0.7124 0.051 Uiso 1 1 calc R . .
C7 C 0.7955(19) 0.9539(13) 0.7254(4) 0.038(2) Uani 1 1 d . B .
H7 H 0.6076 0.9613 0.7123 0.046 Uiso 1 1 calc R . .
N2 N 0.8276(15) 0.9521(15) 0.7929(4) 0.046(2) Uani 1 1 d . . .
H2 H 0.9837 0.9560 0.8115 0.055 Uiso 1 1 calc R B .
C9 C 0.6295(17) 0.9448(15) 0.8275(4) 0.041(2) Uani 1 1 d . B .
O4 O 0.7195(14) 0.9413(14) 0.8892(3) 0.061(2) Uani 1 1 d . . .
O3 O 0.4029(14) 0.9451(14) 0.8090(3) 0.060(2) Uani 1 1 d . . .
C11 C 0.745(3) 0.7189(15) 0.7196(6) 0.069(2) Uani 1 1 d DU A .
C12 C 0.968(9) 1.3045(19) 0.6893(12) 0.28(3) Uani 1 1 d . . .
H12A H 0.9192 1.2886 0.6455 0.424 Uiso 1 1 calc R B 1
H12B H 1.1551 1.3119 0.6965 0.424 Uiso 1 1 calc R B 1
H12C H 0.8880 1.3826 0.7015 0.424 Uiso 1 1 calc R B 1
C14 C 0.517(3) 0.930(4) 0.9316(7) 0.142(11) Uani 1 1 d . B .
H14A H 0.4592 0.8421 0.9340 0.171 Uiso 1 1 calc R . .
H14B H 0.3670 0.9828 0.9173 0.171 Uiso 1 1 calc R . .
O6B O 0.755(4) 0.687(2) 0.7728(7) 0.069(2) Uani 0.50 1 d PDU A 2
O6A O 0.529(4) 0.696(2) 0.7035(9) 0.069(2) Uani 0.50 1 d PDU A 1

loop_
_atom_site_aniso_label
_atom_site_aniso_U_11
_atom_site_aniso_U_22
_atom_site_aniso_U_33
_atom_site_aniso_U_23
_atom_site_aniso_U_13
_atom_site_aniso_U_12
C5A 0.079(4) 0.058(4) 0.069(5) -0.006(4) 0.006(4) -0.013(3)
C18A 0.093(19) 0.046(14) 0.054(15) -0.024(12) -0.014(13) 0.006(13)
C10A 0.16(3) 0.058(11) 0.024(15) 0.014(7) 0.01(3) 0.046(16)
C10B 0.16(3) 0.058(11) 0.024(15) 0.014(7) 0.01(3) 0.046(16)
C5B 0.079(4) 0.058(4) 0.069(5) -0.006(4) 0.006(4) -0.013(3)
C18B 0.069(15) 0.066(16) 0.050(13) -0.035(12) -0.011(11) 0.047(14)
O5A 0.079(4) 0.058(4) 0.069(5) -0.006(4) 0.006(4) -0.013(3)
O5B 0.079(4) 0.058(4) 0.069(5) -0.006(4) 0.006(4) -0.013(3)
C13 0.100(12) 0.41(4) 0.044(8) -0.015(16) 0.015(8) -0.081(19)
C15 0.151(18) 0.40(4) 0.141(17) -0.05(3) -0.060(15) -0.04(3)
C16 0.170(19) 0.44(4) 0.129(18) -0.06(3) -0.075(16) -0.06(3)
C19 0.19(2) 0.47(5) 0.081(14) -0.06(2) 0.021(15) -0.11(3)
C20 0.32(3) 0.48(5) 0.076(14) 0.00(2) -0.01(2) -0.14(3)
C23 0.30(3) 0.44(4) 0.062(12) 0.00(2) 0.002(17) -0.13(3)
C3 0.045(6) 0.023(5) 0.047(6) -0.008(5) 0.013(5) -0.011(5)
C2 0.028(4) 0.026(4) 0.031(4) 0.003(5) 0.006(3) -0.001(5)
C4 0.023(4) 0.023(5) 0.038(5) -0.003(4) 0.004(4) -0.010(4)
C1 0.026(4) 0.043(5) 0.032(4) -0.007(5) 0.009(3) -0.006(5)
O1 0.024(3) 0.038(3) 0.024(3) 0.003(4) 0.001(2) -0.003(3)
C5 0.028(4) 0.029(4) 0.023(4) 0.001(5) -0.006(3) 0.002(5)
O2 0.024(3) 0.047(4) 0.037(3) 0.006(4) -0.008(2) 0.002(3)
N1 0.024(3) 0.059(5) 0.024(3) 0.007(5) -0.002(3) 0.016(5)
C6 0.053(5) 0.040(5) 0.021(4) -0.003(5) -0.004(4) 0.013(6)
C8 0.049(6) 0.042(6) 0.038(6) -0.001(5) 0.013(5) -0.005(5)
C7 0.032(5) 0.060(7) 0.022(5) 0.002(5) 0.000(4) 0.023(5)
N2 0.034(4) 0.080(7) 0.023(4) 0.000(5) -0.004(3) 0.018(5)
C9 0.031(5) 0.056(7) 0.037(5) 0.011(5) 0.003(4) 0.006(5)
O4 0.051(4) 0.111(7) 0.022(3) 0.002(4) 0.004(3) -0.012(5)
O3 0.049(5) 0.094(7) 0.038(4) 0.010(5) 0.004(3) -0.006(5)
C11 0.079(4) 0.058(4) 0.069(5) -0.006(4) 0.006(4) -0.013(3)
C12 0.70(8) 0.033(10) 0.15(2) 0.048(12) 0.21(4) 0.13(2)
C14 0.076(9) 0.31(4) 0.044(7) 0.010(15) 0.032(7) -0.037(17)
O6B 0.079(4) 0.058(4) 0.069(5) -0.006(4) 0.006(4) -0.013(3)
O6A 0.079(4) 0.058(4) 0.069(5) -0.006(4) 0.006(4) -0.013(3)

_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
C5A O5A 1.496(18) . ?
C18A C10A 1.38(16) . ?
C10A C12 1.47(17) . ?
C10A C6 1.4996(11) . ?
C10B C18B 1.17(5) . ?
C10B C6 1.5005(14) . ?
C10B C12 1.62(16) . ?
C5B O5B 1.503(18) . ?
O5A C11 1.377(16) . ?
O5B C11 1.347(17) . ?
C13 C15 1.3900 . ?
C13 C23 1.3900 . ?
C13 C14 1.49(2) . ?
C15 C16 1.3900 . ?
C16 C19 1.3900 . ?
C19 C20 1.3900 . ?
C20 C23 1.3900 . ?
C3 C2 1.513(15) . ?
C2 O1 1.475(9) . ?
C2 C1 1.509(11) . ?
C2 C4 1.515(13) . ?
O1 C5 1.356(9) . ?
C5 O2 1.209(9) . ?
C5 N1 1.331(10) . ?
N1 C6 1.477(10) . ?
C6 C7 1.539(15) . ?
C8 C11 1.447(17) . ?
C8 C7 1.570(15) . ?
C7 N2 1.435(12) . ?
N2 C9 1.313(12) . ?
C9 O3 1.191(11) . ?
C9 O4 1.356(11) . ?
O4 C14 1.444(14) . ?
C11 O6A 1.152(17) . ?
C11 O6B 1.182(16) . ?

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
C18A C10A C12 111(4) . . ?
C18A C10A C6 121(10) . . ?
C12 C10A C6 112(10) . . ?
C18B C10B C6 142(6) . . ?
C18B C10B C12 101(8) . . ?
C6 C10B C12 105(8) . . ?
C11 O5A C5A 99.3(16) . . ?
C11 O5B C5B 100.2(16) . . ?
C15 C13 C23 120.0 . . ?
C15 C13 C14 134.2(16) . . ?
C23 C13 C14 105.1(17) . . ?
C16 C15 C13 120.0 . . ?
C15 C16 C19 120.00(6) . . ?
C20 C19 C16 120.0 . . ?
C19 C20 C23 120.0 . . ?
C20 C23 C13 120.0 . . ?
O1 C2 C1 102.4(6) . . ?
O1 C2 C3 109.6(8) . . ?
C1 C2 C3 111.2(8) . . ?
O1 C2 C4 109.7(8) . . ?
C1 C2 C4 110.6(8) . . ?
C3 C2 C4 112.9(6) . . ?
C5 O1 C2 120.8(6) . . ?
O2 C5 N1 125.1(7) . . ?
O2 C5 O1 125.3(7) . . ?
N1 C5 O1 109.5(6) . . ?
C5 N1 C6 122.2(7) . . ?
N1 C6 C10B 109(7) . . ?
N1 C6 C10A 113(7) . . ?
C10B C6 C10A 12(6) . . ?
N1 C6 C7 106.9(8) . . ?
C10B C6 C7 110(6) . . ?
C10A C6 C7 117(6) . . ?
C11 C8 C7 110.2(9) . . ?
N2 C7 C6 111.2(9) . . ?
N2 C7 C8 110.3(9) . . ?
C6 C7 C8 111.7(7) . . ?
C9 N2 C7 123.0(8) . . ?
O3 C9 N2 126.4(9) . . ?
O3 C9 O4 123.8(9) . . ?
N2 C9 O4 109.8(8) . . ?
C9 O4 C14 114.3(9) . . ?
O6A C11 O6B 100.4(17) . . ?
O6A C11 O5B 19.6(13) . . ?
O6B C11 O5B 117.4(16) . . ?
O6A C11 O5A 115.8(17) . . ?
O6B C11 O5A 40.7(11) . . ?
O5B C11 O5A 121.3(16) . . ?
O6A C11 C8 126.2(16) . . ?
O6B C11 C8 122.6(14) . . ?
O5B C11 C8 116.1(13) . . ?
O5A C11 C8 117.8(12) . . ?
C10A C12 C10B 10(9) . . ?
O4 C14 C13 106.0(13) . . ?

_diffrn_measured_fraction_theta_max 0.997
_diffrn_reflns_theta_full        23.30
_diffrn_measured_fraction_theta_full 0.997
_refine_diff_density_max         0.748
_refine_diff_density_min         -0.709
_refine_diff_density_rms         0.100