# Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry # This journal is © The Royal Society of Chemistry 2011 data_global _journal_name_full Org.Biomol.Chem. _journal_coden_cambridge 0177 _journal_year ? _journal_volume ? _journal_page_first ? _publ_contact_author_email matilde.marques@ist.utl.pt _publ_contact_author_name 'M.M. Marques' loop_ _publ_author_name 'A. Antunes' 'D. Novais' 'J.Ferreira da Silva' 'P.P Santos' M.C.Oliveira 'F. Beland' 'M.Matilde Marques' data_aa23c _database_code_depnum_ccdc_archive 'CCDC 821404' #TrackingRef '4999_web_deposit_cif_file_0_JoaoFerreiradaSilva_1302539089.cif' _audit_creation_method SHELXL-97 _chemical_name_systematic ; 1'-cyclopropyl-4-methyl-1H,1'H-spiro[pyridine-2,2'- pyrido[2,3-d]pyrimidine]-3,4',6(3'H)-trione ; _chemical_name_common ? _chemical_melting_point ? _chemical_formula_moiety ? _chemical_formula_sum 'C33 H34 N8 O7' _chemical_formula_weight 654.68 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' _symmetry_cell_setting Monoclinic _symmetry_space_group_name_H-M C2/c loop_ _symmetry_equiv_pos_as_xyz 'x, y, z' '-x, y, -z+1/2' 'x+1/2, y+1/2, z' '-x+1/2, y+1/2, -z+1/2' '-x, -y, -z' 'x, -y, z-1/2' '-x+1/2, -y+1/2, -z' 'x+1/2, -y+1/2, z-1/2' _cell_length_a 21.528(10) _cell_length_b 8.433(4) _cell_length_c 17.211(8) _cell_angle_alpha 90.00 _cell_angle_beta 94.650(16) _cell_angle_gamma 90.00 _cell_volume 3114(3) _cell_formula_units_Z 4 _cell_measurement_temperature 150(2) _cell_measurement_reflns_used 2973 _cell_measurement_theta_min 3.57 _cell_measurement_theta_max 25.88 _exptl_crystal_description ? _exptl_crystal_colour ? _exptl_crystal_size_max 0.22 _exptl_crystal_size_mid 0.11 _exptl_crystal_size_min 0.05 _exptl_crystal_density_meas ? _exptl_crystal_density_diffrn 1.396 _exptl_crystal_density_method 'not measured' _exptl_crystal_F_000 1376 _exptl_absorpt_coefficient_mu 0.101 _exptl_absorpt_correction_type multi-scan _exptl_absorpt_correction_T_min 0.9782 _exptl_absorpt_correction_T_max 0.9950 _exptl_absorpt_process_details SADABS _exptl_special_details ; ? ; _diffrn_ambient_temperature 150(2) _diffrn_radiation_wavelength 0.71073 _diffrn_radiation_type MoK\a _diffrn_radiation_source 'fine-focus sealed tube' _diffrn_radiation_monochromator graphite _diffrn_measurement_device_type ? _diffrn_measurement_method ? _diffrn_detector_area_resol_mean ? _diffrn_standards_number ? _diffrn_standards_interval_count ? _diffrn_standards_interval_time ? _diffrn_standards_decay_% ? _diffrn_reflns_number 13236 _diffrn_reflns_av_R_equivalents 0.1230 _diffrn_reflns_av_sigmaI/netI 0.1332 _diffrn_reflns_limit_h_min -26 _diffrn_reflns_limit_h_max 25 _diffrn_reflns_limit_k_min -10 _diffrn_reflns_limit_k_max 10 _diffrn_reflns_limit_l_min -19 _diffrn_reflns_limit_l_max 20 _diffrn_reflns_theta_min 3.57 _diffrn_reflns_theta_max 25.88 _reflns_number_total 2973 _reflns_number_gt 1551 _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^)+(0.0496P)^2^+0.0000P] 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 mixed _refine_ls_extinction_method SHELXL _refine_ls_extinction_coef 0.0042(5) _refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^ _refine_ls_number_reflns 2973 _refine_ls_number_parameters 229 _refine_ls_number_restraints 0 _refine_ls_R_factor_all 0.1389 _refine_ls_R_factor_gt 0.0591 _refine_ls_wR_factor_ref 0.1384 _refine_ls_wR_factor_gt 0.1096 _refine_ls_goodness_of_fit_ref 0.954 _refine_ls_restrained_S_all 0.954 _refine_ls_shift/su_max 0.000 _refine_ls_shift/su_mean 0.000 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 C12 C 0.87760(15) 0.6242(3) 0.4729(2) 0.0287(9) Uani 1 1 d . . . H12A H 0.8947 0.6620 0.4252 0.043 Uiso 1 1 calc R . . H12B H 0.8872 0.7010 0.5150 0.043 Uiso 1 1 calc R . . H12C H 0.8323 0.6125 0.4637 0.043 Uiso 1 1 calc R . . C18 C 0.94104(17) 0.2059(5) 0.2438(2) 0.0505(11) Uani 1 1 d . . . H18A H 0.9056 0.2787 0.2444 0.076 Uiso 1 1 calc R . . H18B H 0.9408 0.1326 0.2879 0.076 Uiso 1 1 calc R . . H18C H 0.9379 0.1457 0.1949 0.076 Uiso 1 1 calc R . . C17 C 1.0000 0.2981(6) 0.2500 0.0391(14) Uani 1 2 d S . . O16 O 1.0000 0.4384(5) 0.2500 0.108(2) Uani 1 2 d S . . H1 H 0.9683(14) 0.068(4) 0.5536(17) 0.025(9) Uiso 1 1 d . . . H3' H 0.9805(16) 0.240(4) 0.6812(19) 0.043(11) Uiso 1 1 d . . . O14 O 1.00442(10) 0.1583(2) 0.43330(13) 0.0281(6) Uani 1 1 d . . . O15 O 0.92939(10) 0.2261(3) 0.80310(13) 0.0295(6) Uani 1 1 d . . . N1' N 0.85305(11) 0.1330(3) 0.58283(14) 0.0196(6) Uani 1 1 d . . . O13 O 0.86629(10) 0.4799(2) 0.61995(13) 0.0300(6) Uani 1 1 d . . . N1 N 0.95700(12) 0.1687(3) 0.54548(15) 0.0190(6) Uani 1 1 d . . . N3' N 0.93755(13) 0.2169(3) 0.67300(15) 0.0203(6) Uani 1 1 d . . . N8' N 0.75315(12) 0.1084(3) 0.62555(15) 0.0252(7) Uani 1 1 d . . . C2 C 0.91101(14) 0.2288(3) 0.59369(17) 0.0184(7) Uani 1 1 d . . . C4'A C 0.83747(15) 0.1792(3) 0.71995(18) 0.0196(8) Uani 1 1 d . . . C4' C 0.90443(15) 0.2116(3) 0.73630(19) 0.0210(8) Uani 1 1 d . . . C9 C 0.82352(15) 0.1328(3) 0.50397(17) 0.0213(8) Uani 1 1 d . . . H9 H 0.8037 0.2349 0.4857 0.026 Uiso 1 1 calc R . . C5' C 0.79766(15) 0.1810(3) 0.77857(19) 0.0246(8) Uani 1 1 d . . . H5' H 0.8128 0.2075 0.8303 0.029 Uiso 1 1 calc R . . C8'A C 0.81391(14) 0.1417(3) 0.64409(18) 0.0189(7) Uani 1 1 d . . . C4 C 0.90609(14) 0.4671(3) 0.49574(18) 0.0199(8) Uani 1 1 d . . . C6 C 0.97007(14) 0.2293(3) 0.47557(19) 0.0220(8) Uani 1 1 d . . . C5 C 0.94279(14) 0.3833(3) 0.45199(18) 0.0222(8) Uani 1 1 d . . . H5 H 0.9517 0.4257 0.4030 0.027 Uiso 1 1 calc R . . C7' C 0.71618(15) 0.1093(4) 0.68498(19) 0.0288(8) Uani 1 1 d . . . H7' H 0.6734 0.0839 0.6733 0.035 Uiso 1 1 calc R . . C11 C 0.79124(15) -0.0145(3) 0.47470(18) 0.0254(8) Uani 1 1 d . . . H11A H 0.7925 -0.1075 0.5099 0.030 Uiso 1 1 calc R . . H11B H 0.7521 -0.0025 0.4408 0.030 Uiso 1 1 calc R . . C3 C 0.89344(14) 0.4031(3) 0.57234(19) 0.0210(8) Uani 1 1 d . . . C6' C 0.73547(15) 0.1441(4) 0.76178(19) 0.0285(8) Uani 1 1 d . . . H6' H 0.7071 0.1428 0.8013 0.034 Uiso 1 1 calc R . . C10 C 0.85047(15) 0.0339(3) 0.44231(18) 0.0268(8) Uani 1 1 d . . . H10A H 0.8480 0.0762 0.3885 0.032 Uiso 1 1 calc R . . H10B H 0.8884 -0.0289 0.4576 0.032 Uiso 1 1 calc R . . 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 C12 0.027(2) 0.0271(18) 0.033(2) 0.0056(15) 0.0096(17) -0.0002(15) C18 0.034(3) 0.075(3) 0.045(3) -0.007(2) 0.019(2) -0.004(2) C17 0.042(4) 0.041(3) 0.036(3) 0.000 0.013(3) 0.000 O16 0.111(4) 0.028(3) 0.179(6) 0.000 -0.020(4) 0.000 O14 0.0244(14) 0.0388(13) 0.0234(14) -0.0010(10) 0.0165(11) 0.0069(10) O15 0.0185(14) 0.0549(15) 0.0156(14) -0.0025(11) 0.0043(11) 0.0009(11) N1' 0.0155(15) 0.0277(14) 0.0162(16) -0.0011(11) 0.0060(12) 0.0003(11) O13 0.0360(15) 0.0292(13) 0.0272(15) 0.0002(10) 0.0176(12) 0.0062(10) N1 0.0157(16) 0.0239(15) 0.0188(16) 0.0045(12) 0.0105(13) 0.0036(12) N3' 0.0142(17) 0.0318(15) 0.0158(16) 0.0004(12) 0.0060(13) 0.0004(12) N8' 0.0150(16) 0.0358(16) 0.0260(17) -0.0016(12) 0.0086(13) -0.0015(12) C2 0.0120(18) 0.0281(17) 0.0160(18) -0.0023(14) 0.0063(15) -0.0007(13) C4'A 0.0167(19) 0.0249(17) 0.0184(19) 0.0002(13) 0.0086(15) 0.0015(13) C4' 0.0165(19) 0.0273(17) 0.020(2) 0.0012(15) 0.0074(17) 0.0041(14) C9 0.026(2) 0.0237(17) 0.0152(18) -0.0020(13) 0.0061(15) 0.0032(14) C5' 0.024(2) 0.0334(19) 0.0167(19) 0.0022(14) 0.0077(16) 0.0013(15) C8'A 0.0161(19) 0.0214(17) 0.021(2) 0.0032(13) 0.0105(16) 0.0022(13) C4 0.0158(18) 0.0233(17) 0.021(2) 0.0008(14) 0.0026(15) -0.0045(14) C6 0.0140(19) 0.0314(18) 0.022(2) 0.0004(15) 0.0071(16) -0.0039(14) C5 0.024(2) 0.0283(17) 0.0157(18) 0.0064(14) 0.0070(16) -0.0037(15) C7' 0.0157(19) 0.043(2) 0.028(2) 0.0021(16) 0.0086(17) -0.0028(16) C11 0.021(2) 0.0347(19) 0.0213(19) -0.0077(15) 0.0089(16) -0.0029(15) C3 0.0129(18) 0.0292(18) 0.0216(19) 0.0001(15) 0.0058(15) -0.0022(14) C6' 0.020(2) 0.044(2) 0.023(2) 0.0006(16) 0.0104(17) 0.0008(16) C10 0.028(2) 0.0333(18) 0.021(2) -0.0082(15) 0.0107(17) -0.0002(15) _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 C12 C4 1.499(4) . ? C12 H12A 0.9800 . ? C12 H12B 0.9800 . ? C12 H12C 0.9800 . ? C18 C17 1.485(4) . ? C18 H18A 0.9800 . ? C18 H18B 0.9800 . ? C18 H18C 0.9800 . ? C17 O16 1.183(6) . ? C17 C18 1.485(4) 2_755 ? O14 C6 1.234(3) . ? O15 C4' 1.235(4) . ? N1' C8'A 1.404(3) . ? N1' C9 1.451(4) . ? N1' C2 1.486(4) . ? O13 C3 1.229(3) . ? N1 C6 1.358(4) . ? N1 C2 1.435(3) . ? N1 H1 0.89(3) . ? N3' C4' 1.350(4) . ? N3' C2 1.440(4) . ? N3' H3' 0.94(3) . ? N8' C7' 1.346(3) . ? N8' C8'A 1.351(4) . ? C2 C3 1.555(4) . ? C4'A C5' 1.376(4) . ? C4'A C8'A 1.398(4) . ? C4'A C4' 1.472(4) . ? C9 C11 1.491(4) . ? C9 C10 1.503(4) . ? C9 H9 1.0000 . ? C5' C6' 1.382(4) . ? C5' H5' 0.9500 . ? C4 C5 1.337(4) . ? C4 C3 1.470(4) . ? C6 C5 1.469(4) . ? C5 H5 0.9500 . ? C7' C6' 1.385(4) . ? C7' H7' 0.9500 . ? C11 C10 1.489(4) . ? C11 H11A 0.9900 . ? C11 H11B 0.9900 . ? C6' H6' 0.9500 . ? C10 H10A 0.9900 . ? C10 H10B 0.9900 . ? 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 C4 C12 H12A 109.5 . . ? C4 C12 H12B 109.5 . . ? H12A C12 H12B 109.5 . . ? C4 C12 H12C 109.5 . . ? H12A C12 H12C 109.5 . . ? H12B C12 H12C 109.5 . . ? C17 C18 H18A 109.5 . . ? C17 C18 H18B 109.5 . . ? H18A C18 H18B 109.5 . . ? C17 C18 H18C 109.5 . . ? H18A C18 H18C 109.5 . . ? H18B C18 H18C 109.5 . . ? O16 C17 C18 121.6(2) . . ? O16 C17 C18 121.6(2) . 2_755 ? C18 C17 C18 116.9(5) . 2_755 ? C8'A N1' C9 117.3(2) . . ? C8'A N1' C2 115.2(2) . . ? C9 N1' C2 114.7(2) . . ? C6 N1 C2 125.6(3) . . ? C6 N1 H1 115.1(19) . . ? C2 N1 H1 116.0(18) . . ? C4' N3' C2 124.9(3) . . ? C4' N3' H3' 117(2) . . ? C2 N3' H3' 116(2) . . ? C7' N8' C8'A 116.1(3) . . ? N1 C2 N3' 106.5(2) . . ? N1 C2 N1' 110.3(2) . . ? N3' C2 N1' 110.2(2) . . ? N1 C2 C3 111.3(2) . . ? N3' C2 C3 111.1(2) . . ? N1' C2 C3 107.4(2) . . ? C5' C4'A C8'A 119.1(3) . . ? C5' C4'A C4' 121.1(3) . . ? C8'A C4'A C4' 119.7(3) . . ? O15 C4' N3' 122.0(3) . . ? O15 C4' C4'A 122.8(3) . . ? N3' C4' C4'A 115.1(3) . . ? N1' C9 C11 118.3(3) . . ? N1' C9 C10 119.8(3) . . ? C11 C9 C10 59.67(19) . . ? N1' C9 H9 115.8 . . ? C11 C9 H9 115.8 . . ? C10 C9 H9 115.8 . . ? C4'A C5' C6' 119.7(3) . . ? C4'A C5' H5' 120.2 . . ? C6' C5' H5' 120.2 . . ? N8' C8'A C4'A 122.6(3) . . ? N8' C8'A N1' 116.1(3) . . ? C4'A C8'A N1' 121.3(3) . . ? C5 C4 C3 118.2(3) . . ? C5 C4 C12 124.6(3) . . ? C3 C4 C12 117.2(3) . . ? O14 C6 N1 121.1(3) . . ? O14 C6 C5 120.8(3) . . ? N1 C6 C5 118.1(3) . . ? C4 C5 C6 123.6(3) . . ? C4 C5 H5 118.2 . . ? C6 C5 H5 118.2 . . ? N8' C7' C6' 125.2(3) . . ? N8' C7' H7' 117.4 . . ? C6' C7' H7' 117.4 . . ? C10 C11 C9 60.57(19) . . ? C10 C11 H11A 117.7 . . ? C9 C11 H11A 117.7 . . ? C10 C11 H11B 117.7 . . ? C9 C11 H11B 117.7 . . ? H11A C11 H11B 114.8 . . ? O13 C3 C4 122.5(3) . . ? O13 C3 C2 117.4(3) . . ? C4 C3 C2 120.0(3) . . ? C5' C6' C7' 117.3(3) . . ? C5' C6' H6' 121.4 . . ? C7' C6' H6' 121.4 . . ? C11 C10 C9 59.76(19) . . ? C11 C10 H10A 117.8 . . ? C9 C10 H10A 117.8 . . ? C11 C10 H10B 117.8 . . ? C9 C10 H10B 117.8 . . ? H10A C10 H10B 114.9 . . ? loop_ _geom_torsion_atom_site_label_1 _geom_torsion_atom_site_label_2 _geom_torsion_atom_site_label_3 _geom_torsion_atom_site_label_4 _geom_torsion _geom_torsion_site_symmetry_1 _geom_torsion_site_symmetry_2 _geom_torsion_site_symmetry_3 _geom_torsion_site_symmetry_4 _geom_torsion_publ_flag C6 N1 C2 N3' -141.0(3) . . . . ? C6 N1 C2 N1' 99.3(3) . . . . ? C6 N1 C2 C3 -19.8(4) . . . . ? C4' N3' C2 N1 -157.5(3) . . . . ? C4' N3' C2 N1' -37.8(4) . . . . ? C4' N3' C2 C3 81.1(3) . . . . ? C8'A N1' C2 N1 158.5(2) . . . . ? C9 N1' C2 N1 -60.8(3) . . . . ? C8'A N1' C2 N3' 41.1(3) . . . . ? C9 N1' C2 N3' -178.1(2) . . . . ? C8'A N1' C2 C3 -80.1(3) . . . . ? C9 N1' C2 C3 60.7(3) . . . . ? C2 N3' C4' O15 -168.6(3) . . . . ? C2 N3' C4' C4'A 14.5(4) . . . . ? C5' C4'A C4' O15 7.4(4) . . . . ? C8'A C4'A C4' O15 -170.8(3) . . . . ? C5' C4'A C4' N3' -175.7(3) . . . . ? C8'A C4'A C4' N3' 6.1(4) . . . . ? C8'A N1' C9 C11 -74.3(3) . . . . ? C2 N1' C9 C11 145.7(3) . . . . ? C8'A N1' C9 C10 -143.7(3) . . . . ? C2 N1' C9 C10 76.4(3) . . . . ? C8'A C4'A C5' C6' 0.7(4) . . . . ? C4' C4'A C5' C6' -177.5(3) . . . . ? C7' N8' C8'A C4'A -1.6(4) . . . . ? C7' N8' C8'A N1' 176.9(2) . . . . ? C5' C4'A C8'A N8' 0.7(4) . . . . ? C4' C4'A C8'A N8' 178.9(3) . . . . ? C5' C4'A C8'A N1' -177.8(2) . . . . ? C4' C4'A C8'A N1' 0.5(4) . . . . ? C9 N1' C8'A N8' 16.4(4) . . . . ? C2 N1' C8'A N8' 156.1(2) . . . . ? C9 N1' C8'A C4'A -165.0(3) . . . . ? C2 N1' C8'A C4'A -25.3(4) . . . . ? C2 N1 C6 O14 -170.4(3) . . . . ? C2 N1 C6 C5 10.4(4) . . . . ? C3 C4 C5 C6 1.4(5) . . . . ? C12 C4 C5 C6 -179.9(3) . . . . ? O14 C6 C5 C4 -178.9(3) . . . . ? N1 C6 C5 C4 0.3(5) . . . . ? C8'A N8' C7' C6' 1.3(4) . . . . ? N1' C9 C11 C10 -109.8(3) . . . . ? C5 C4 C3 O13 171.5(3) . . . . ? C12 C4 C3 O13 -7.4(5) . . . . ? C5 C4 C3 C2 -12.3(4) . . . . ? C12 C4 C3 C2 168.9(3) . . . . ? N1 C2 C3 O13 -163.3(3) . . . . ? N3' C2 C3 O13 -44.8(4) . . . . ? N1' C2 C3 O13 75.8(3) . . . . ? N1 C2 C3 C4 20.2(4) . . . . ? N3' C2 C3 C4 138.8(3) . . . . ? N1' C2 C3 C4 -100.6(3) . . . . ? C4'A C5' C6' C7' -1.1(4) . . . . ? N8' C7' C6' C5' 0.0(5) . . . . ? N1' C9 C10 C11 107.3(3) . . . . ? _diffrn_measured_fraction_theta_max 0.979 _diffrn_reflns_theta_full 25.88 _diffrn_measured_fraction_theta_full 0.979 _refine_diff_density_max 0.262 _refine_diff_density_min -0.288 _refine_diff_density_rms 0.062