Supporting information (+)- and ( )-Ecarlottones, Uncommon Chalconoids from Fissistigma latifolium with Proapoptotic Activity Charlotte Gény, Alma Abou Samra, Pascal Retailleau, Bogdan I. Iorga, Hristo Nedev, Khalijah Awang, Fanny Roussi, Marc Litaudon,,* and Vincent Dumontet,* Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR201, Université Paris-Saclay, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France. Department of Chemistry, Faculty of Science, University Malaya, Kuala Lumpur 00, Malaysia. Corresponding Author *Tel: +(0)198208. Fax: +(0)1902. E-mail: vincent.dumontet@cnrs.fr (V. D.). *Tel: +(0)198208. Fax: +(0)1902. E-mail: marc.litaudon@cnrs.fr (M. L.).
List of Supporting information S1. 1 H NMR (00 MHz, CDCl ) spectra of the new compound 1 at various temperatures S2. 1 H NMR (00 MHz, CDCl at 2 K) spectrum of the new compound 1 S. 1 C NMR (10 MHz, CDCl at 2 K) spectrum of the new compound 1 S. HSQC (00 MHz, CDCl at 2 K) spectrum of the new compound 1 S. HMBC (00 MHz, CDCl at 2 K) spectrum of the new compound 1 S. Structure refinement details of the new compounds (+)-1 and ( )-1 S. (a) Superposed experimental ECD spectrum of (+)-ecarlottone (black) with the computed ECD spectrum (red) starting from the X-ray structure of 1 (S,S); (b) X-ray structure of 1 (S,S); (c) Superposed experimental ECD spectrum of ( )-ecarlottone (black) with the computed ECD spectrum (red) starting from the X-ray structure of 1 (R,R); (d) X-ray structure of 1 (R,R). S8. 1 H NMR (00 MHz, CDCl at 2 K) spectrum of compound S9. 1 H NMR (00 MHz, CDCl ) spectrum of the new compound S10. 1 C NMR ( MHz, CDCl ) spectrum of the new compound S11. HSQC (00 MHz, CDCl ) spectrum of the new compound S12. HMBC (00 MHz, CDCl ) spectrum of the new compound S1. 1 H NMR (00 MHz, CDCl ) spectrum of the new compound S1. 1 C NMR (1 MHz, CDCl ) spectrum of the new compound S1. HSQC (00 MHz, CDCl ) spectrum of the new compound S1. HMBC (00 MHz, CDCl ) spectrum of the new compound S1. 1 H NMR (00 MHz, CDCl ) spectrum of the new compound S18. 1 C NMR (1 MHz, CDCl ) spectrum of the new compound S19. HSQC (00 MHz, CDCl ) spectrum of the new compound S20. HMBC (00 MHz, CDCl ) spectrum of the new compound S21. Raw data used for Table and their graphical representation
S1. 1 H NMR (00 MHz, CDCl ) spectra of the new compound 1 at various temperatures 11 12 10 '' '' '' 8 9 H '' '' 2'' 2 1'' H ' 1 1' 2' 22 K ' ' ' 2 K 2 K 2 K 2 K 298 K
S2. 1 H NMR (00 MHz, CDCl at 2 K) spectrum of the new compound 1 11 12 10 '' '' '' 8 9 H '' '' 2'' 2 1'' H ' 1 1' 2' ' ' '
S. 1 C NMR (10 MHz, CDCl at 2 K) spectrum of the new compound 1 11 12 10 '' '' '' 8 9 H '' '' 2'' 2 1'' H ' 1 1' 2' ' ' '
S. HSQC (00 MHz, CDCl at 2 K) spectrum of the new compound 1 11 12 10 '' '' '' 8 9 H '' '' 2'' 2 1'' H ' 1 1' 2' ' ' '
S. HMBC (00 MHz, CDCl at 2 K) spectrum of the new compound 1 11 12 10 '' '' '' 8 9 H '' '' 2'' 2 1'' H ' 1 1' 2' ' ' '
S. Structure refinement details of the new compounds (+)-1 and ( )-1 X-ray diffraction experiment on compounds (+)-1 and ( )-1 were performed on a Rigaku MM00 HF rotating-anode diffractometer, equipped with a Rapid II curved Image Plate detector and using Cu-Ka radiation (l =1.18 Å). A suitable red single crystal obtained in a mixture of acetonitrile methanol solvent was irradiated at low temperature (19K). frames of -degree oscillations segmented in three omega-scans allowed us to record complete dataset in the 2q range of 1-1.. Data reduction and scaling were carried out with an empirical absorption correction, as well as a treatment for Lorentz and polarization effects using the program Fs_Process. 1 The structure was solved by direct methods (Shelxs- 9) 2 in the space group P 2 1 /c (n 1), then refined by full matrix least squares on F 2 using the SHELXL-201/. Anisotropic thermal parameters were used for all non-hydrogen atoms and if most of the H atoms were located in residual maps they all were refined as riding, with U eq values set at 1.2U eq (parent atom) (1. for the methyl groups or hydroxyl oxygen atoms). The racemic compound is found in the asymmetric unit in a head-to-tail dimeric assembly. Tables (S1-S) on crystallographic data collection, crystal model statistics and geometry details are shown below. The crystallographic data of (+)-1 and ( )-1 have been deposited in the Cambridge Crystallographic Data Centre as CCDC 19889 and are available free of charge via http://www.ccdc.cam.ac.uk/data_request/cif. References: (1) Rigaku. (2009) Fs_Process as implemented within CrystalClear-SM Expert 2.0 r Rigaku Corporation, Tokyo, Japan. (2) Sheldrick, G. M. (2008). Acta Cryst. A, 112-122. () Sheldrick, G. M. (201). Acta Cryst. C1, -8. () Burnett, M. N. & Johnson, C. K. (199). RTEPIII. Report RNL-89. ak Ridge National Laboratory, Tennessee, USA. Figure S1. RTEP view of compound (+)-1 and ( )-1in the asymmetric unit.
Table S1. Crystal data and structure refinement for (+)-1 and ( )-1. Identification code (+)-1 and ( )-1 Empirical formula C 2 H 28 Formula weight.8 Temperature 19(2) K Wavelength 1.18 Å Crystal system Monoclinic Space group P2 1 /c Unit cell dimensions a = 2.21(18) Å a= 90. b =.8() Å b= 108.1(8). c = 2.9(19) Å g= 90. Volume.() Å Z 8 Density (calculated) 1.2 Mg/m Absorption coefficient 0. mm-1 F(000) 18 Crystal size 0.28 x 0.2 x 0.08 mm Theta range for data collection.1 to 8.221. Index ranges -21 h 29, -8 k 8, -2 l 0 Reflections collected 2198 Independent reflections 8181 [R(int) = 0.08] Completeness to theta =.8 98. % Absorption correction Semi-empirical from equivalents Max. and min. transmission 0.9 and 0.9 Refinement method Full-matrix least-squares on F2 Data / restraints / parameters 81 / 0 / 8 Goodness-of-fit on F2 1.01 Final R indices [I>2s(I)] R1 = 0.09, wr2 = 0.18 R indices (all data) R1 = 0.109, wr2 = 0.102 Largest diff. peak and hole 0.2 and -0.229 e.å- Table S2. Atomic coordinates (x 10 ) and equivalent isotropic displacement parameters (Å 2 x 10 ) for (+)-1 and ( )-1. U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. x y z U(eq) C(1) 02(1) -2() 29(1) (1) (1) 98(1) 290(2) 8(1) (1) C(2) 0(1) -10() 98(1) (1) (2) 09(1) 91(2) 880(1) (1) () 2(1) () 8(1) 98(1) C() 9(1) -2088() 02(1) (1) C() 10(1) -08() 82(1) 8(1) () 22(2) 2() 9(1) 120(1) C() 0(1) -22() 290(1) (1) () (1) -2() 29(1) 82(1) C() 2(1) -82() (1) (1) () 09(1) -1() 0(1) (1)
C() 91(1) 19() 22(1) 1(1) C(8) 20(1) 1() 89(1) 8(1) C(9) 9(1) 21() 12(1) (1) C(10) 0(1) 0() 80(1) (1) C(11) (2) 28() 2(1) (1) C(12) 8(1) 9() 1(1) (1) C(1) 111(1) () 00(1) 2(1) C(1) 02(2) 0() 12(2) 8(1) C(1) 9(1) () 89(1) (1) C(1) 91(2) 1() 290(1) (1) C(1) 0(2) 211() 22(2) 8(1) C(18) 9(2) 2() 29(2) 89(1) C(19) 9(2) 18() 2(2) (1) C(20) 1(1) 8() 2(1) (1) C(21) 29(1) -9() 9(1) (1) C(22) 89(1) -2() 88(1) (1) C(2) 9(1) -9() 0(1) 8(1) C(2) 819(2) -00() 2(2) 80(1) C(2) 82(2) -998() 08(2) 1() C(2) 8(2) -211(8) 298(2) 120(2) (1B) 89(1) 80(2) 08(1) 2(1) C(1B) 88(1) 8() 2(1) 0(1) (2B) 8(1) -19(2) 1(1) 1(1) C(2B) 82(1) () 0(1) 0(1) (B) 980(1) -21(2) 09(1) (1) C(B) 89(1) () 1(1) (1) (B) 982(1) 1() 088(1) 8(1) C(B) 9(1) () 22(1) (1) (B) 98(1) 01() 0(1) 9(1) C(B) (1) 8() (1) 1(1) (B) 900(1) 8(2) 91(1) 0(1) C(B) 80(1) 1() 0(1) 9(1) C(B) 88(1) 199() 0(1) 8(1) C(8B) 88(1) 12() 12(1) (1) C(9B) 90(1) 22() 88(1) 8(1) C(10B) 91(1) 289() 9(1) 8(1) C(11B) 909(1) 908() 90(1) (1) C(12B) 928(1) -0() 1(1) (1) C(1B) 891(1) -() 9(1) 9(1) C(1B) 1008(2) 1() 9(1) (1) C(1B) 921(1) 1() 9(1) (1) C(1B) 90(1) 8() 9(1) 2(1) C(1B) 102(1) 1() 2(1) 1(1) C(18B) 101(1) 22() 10(1) (1) C(19B) 992(2) 19() 0(1) 9(1) C(20B) 90(1) 222() 01(1) 8(1) C(21B) 80(1) 81() 8(1) 2(1) C(22B) 29(1) 908() 18(1) (1) C(2B) 1(1) 10918() 98(1) (1) C(2B) 88(1) 11() 2(1) (1) C(2B) (2) 9992(8) 9(2) 1(2) C(2B) 80(2) 121() 90(2) 122(2)
Table S. Bond lengths [Å] and angles [ ] for (+)-1 and ( )-1. C(1)-C() 1.99() C(1)-C() 1.() C(1)-C(2) 1.0() C(1)-H(1) 1.0000 (1)-C() 1.1() (1)-H(1) 0.800 C(2)-C(1) 1.01() C(2)-C() 1.0() C(2)-H(2) 1.0000 (2)-C(1) 1.2() ()-C(12) 1.() ()-H(1) 0.800 C()-C() 1.0() C()-H(A) 0.9900 C()-H(B) 0.9900 C()-C() 1.1() C()-C(21) 1.1() ()-C(11) 1.1() ()-C(1) 1.2() C()-C() 1.99() C()-H() 0.900 ()-C(10) 1.21() C()-H(A) 0.9900 C()-H(B) 0.9900 ()-C(9) 1.218() C()-C(8) 1.89() C(8)-C(1) 1.2() C(8)-C(9) 1.0() C(9)-C(10) 1.() C(10)-C(11) 1.() C(11)-C(12) 1.() C(12)-C(1) 1.8() C(1)-H(1A) 0.9800 C(1)-H(1B) 0.9800 C(1)-H(1C) 0.9800 C(1)-C(20) 1.80() C(1)-C(1) 1.02() C(1)-C(1) 1.() C(1)-H(1) 0.900 C(1)-C(18) 1.9() C(1)-H(1) 0.900 C(18)-C(19) 1.() C(18)-H(18) 0.900 C(19)-C(20) 1.0() C(19)-H(19) 0.900 C(20)-H(20) 0.900 C(21)-C(22) 1.28() C(21)-H(21A) 0.9900 C(21)-H(21B) 0.9900
C(22)-C(2) 1.8() C(22)-H(22A) 0.9900 C(22)-H(22B) 0.9900 C(2)-C(2) 1.299() C(2)-H(2) 0.900 C(2)-C(2) 1.88() C(2)-C(2) 1.0() C(2)-H(2A) 0.9800 C(2)-H(2B) 0.9800 C(2)-H(2C) 0.9800 C(2)-H(2A) 0.9800 C(2)-H(2B) 0.9800 C(2)-H(2C) 0.9800 (1B)-C(B) 1.1() (1B)-H(1B) 0.800 C(1B)-C(B) 1.99() C(1B)-C(B) 1.() C(1B)-C(2B) 1.0() C(1B)-H(1B) 1.0000 (2B)-C(1B) 1.2() C(2B)-C(1B) 1.11() C(2B)-C(B) 1.1() C(2B)-H(2B) 1.0000 (B)-C(12B) 1.() (B)-H(B) 0.800 C(B)-C(B) 1.98() C(B)-H(BA) 0.9900 C(B)-H(BB) 0.9900 (B)-C(11B) 1.9() (B)-C(1B) 1.11() C(B)-C(B) 1.2() C(B)-C(21B) 1.0() (B)-C(10B) 1.210() C(B)-C(B) 1.02() C(B)-H(B) 0.900 (B)-C(9B) 1.21() C(B)-H(BA) 0.9900 C(B)-H(BB) 0.9900 C(B)-C(8B) 1.9() C(8B)-C(1B) 1.0() C(8B)-C(9B) 1.() C(9B)-C(10B) 1.() C(10B)-C(11B) 1.() C(11B)-C(12B) 1.() C(12B)-C(1B) 1.0() C(1B)-H(1D) 0.9800 C(1B)-H(1E) 0.9800 C(1B)-H(1F) 0.9800 C(1B)-C(1B) 1.8() C(1B)-C(20B) 1.91() C(1B)-C(1B) 1.9() C(1B)-H(1B) 0.900
C(1B)-C(18B) 1.8() C(1B)-H(1B) 0.900 C(18B)-C(19B) 1.8() C(18B)-H(18B) 0.900 C(19B)-C(20B) 1.() C(19B)-H(19B) 0.900 C(20B)-H(20B) 0.900 C(21B)-C(22B) 1.28() C(21B)-H(21C) 0.9900 C(21B)-H(21D) 0.9900 C(22B)-C(2B) 1.0() C(22B)-H(22C) 0.9900 C(22B)-H(22D) 0.9900 C(2B)-C(2B) 1.0() C(2B)-H(2B) 0.900 C(2B)-C(2B) 1.2() C(2B)-C(2B) 1.08() C(2B)-H(2D) 0.9800 C(2B)-H(2E) 0.9800 C(2B)-H(2F) 0.9800 C(2B)-H(2D) 0.9800 C(2B)-H(2E) 0.9800 C(2B)-H(2F) 0.9800 C()-C(1)-C() 109.1(2) C()-C(1)-C(2) 112.(2) C()-C(1)-C(2) 108.(2) C()-C(1)-H(1) 108.9 C()-C(1)-H(1) 108.9 C(2)-C(1)-H(1) 108.9 C()-(1)-H(1) 109. C(1)-C(2)-C() 112.(2) C(1)-C(2)-C(1) 11.8(2) C()-C(2)-C(1) 10.2(2) C(1)-C(2)-H(2) 10. C()-C(2)-H(2) 10. C(1)-C(2)-H(2) 10. C(12)-()-H(1) 109. C()-C()-C(2) 112.9(2) C()-C()-H(A) 109.0 C(2)-C()-H(A) 109.0 C()-C()-H(B) 109.0 C(2)-C()-H(B) 109.0 H(A)-C()-H(B) 10.8 C()-C()-C() 121.1() C()-C()-C(21) 12.() C()-C()-C(21) 11.2(2) C(11)-()-C(1) 12.8() C()-C()-C() 12.() C()-C()-H() 11. C()-C()-H() 11. C()-C()-C(1) 111.9(2)
C()-C()-H(A) 109.2 C(1)-C()-H(A) 109.2 C()-C()-H(B) 109.2 C(1)-C()-H(B) 109.2 H(A)-C()-H(B) 10.9 (1)-C()-C(8) 120.1(2) (1)-C()-C(1) 11.1(2) C(8)-C()-C(1) 12.8(2) C()-C(8)-C(1) 119.1(2) C()-C(8)-C(9) 12.(2) C(1)-C(8)-C(9) 11.(2) ()-C(9)-C(8) 12.0() ()-C(9)-C(10) 11.() C(8)-C(9)-C(10) 118.(2) ()-C(10)-C(11) 122.1() ()-C(10)-C(9) 11.9() C(11)-C(10)-C(9) 119.9() ()-C(11)-C(12) 12.9() ()-C(11)-C(10) 112.() C(12)-C(11)-C(10) 119.() ()-C(12)-C(11) 121.1() ()-C(12)-C(1) 11.1() C(11)-C(12)-C(1) 121.() (2)-C(1)-C(8) 121.() (2)-C(1)-C(12) 11.1(2) C(8)-C(1)-C(12) 122.() ()-C(1)-H(1A) 109. ()-C(1)-H(1B) 109. H(1A)-C(1)-H(1B) 109. ()-C(1)-H(1C) 109. H(1A)-C(1)-H(1C) 109. H(1B)-C(1)-H(1C) 109. C(20)-C(1)-C(1) 11.1() C(20)-C(1)-C(2) 12.0() C(1)-C(1)-C(2) 118.8() C(1)-C(1)-C(1) 121.1() C(1)-C(1)-H(1) 119. C(1)-C(1)-H(1) 119. C(1)-C(1)-C(18) 120.9() C(1)-C(1)-H(1) 119. C(18)-C(1)-H(1) 119. C(19)-C(18)-C(1) 118.8() C(19)-C(18)-H(18) 120. C(1)-C(18)-H(18) 120. C(18)-C(19)-C(20) 121.2() C(18)-C(19)-H(19) 119. C(20)-C(19)-H(19) 119. C(19)-C(20)-C(1) 120.8() C(19)-C(20)-H(20) 119. C(1)-C(20)-H(20) 119. C()-C(21)-C(22) 11.(2) C()-C(21)-H(21A) 108.1
C(22)-C(21)-H(21A) 108.1 C()-C(21)-H(21B) 108.1 C(22)-C(21)-H(21B) 108.1 H(21A)-C(21)-H(21B) 10. C(2)-C(22)-C(21) 11.2() C(2)-C(22)-H(22A) 108. C(21)-C(22)-H(22A) 108. C(2)-C(22)-H(22B) 108. C(21)-C(22)-H(22B) 108. H(22A)-C(22)-H(22B) 10. C(2)-C(2)-C(22) 128.8() C(2)-C(2)-H(2) 11. C(22)-C(2)-H(2) 11. C(2)-C(2)-C(2) 122.() C(2)-C(2)-C(2) 121.9() C(2)-C(2)-C(2) 11.() C(2)-C(2)-H(2A) 109. C(2)-C(2)-H(2B) 109. H(2A)-C(2)-H(2B) 109. C(2)-C(2)-H(2C) 109. H(2A)-C(2)-H(2C) 109. H(2B)-C(2)-H(2C) 109. C(2)-C(2)-H(2A) 109. C(2)-C(2)-H(2B) 109. H(2A)-C(2)-H(2B) 109. C(2)-C(2)-H(2C) 109. H(2A)-C(2)-H(2C) 109. H(2B)-C(2)-H(2C) 109. C(B)-(1B)-H(1B) 109. C(B)-C(1B)-C(B) 109.1(2) C(B)-C(1B)-C(2B) 111.9(2) C(B)-C(1B)-C(2B) 109.(2) C(B)-C(1B)-H(1B) 108. C(B)-C(1B)-H(1B) 108. C(2B)-C(1B)-H(1B) 108. C(1B)-C(2B)-C(B) 110.(2) C(1B)-C(2B)-C(1B) 11.(2) C(B)-C(2B)-C(1B) 10.9(2) C(1B)-C(2B)-H(2B) 10.9 C(B)-C(2B)-H(2B) 10.9 C(1B)-C(2B)-H(2B) 10.9 C(12B)-(B)-H(B) 109. C(B)-C(B)-C(2B) 11.9(2) C(B)-C(B)-H(BA) 108. C(2B)-C(B)-H(BA) 108. C(B)-C(B)-H(BB) 108. C(2B)-C(B)-H(BB) 108. H(BA)-C(B)-H(BB) 10. C(11B)-(B)-C(1B) 12.(2) C(B)-C(B)-C(B) 120.9() C(B)-C(B)-C(21B) 12.1() C(B)-C(B)-C(21B) 11.9(2)
C(B)-C(B)-C(B) 12.() C(B)-C(B)-H(B) 11.8 C(B)-C(B)-H(B) 11.8 C(B)-C(B)-C(1B) 111.8(2) C(B)-C(B)-H(BA) 109. C(1B)-C(B)-H(BA) 109. C(B)-C(B)-H(BB) 109. C(1B)-C(B)-H(BB) 109. H(BA)-C(B)-H(BB) 10.9 (1B)-C(B)-C(8B) 120.2(2) (1B)-C(B)-C(1B) 11.1(2) C(8B)-C(B)-C(1B) 12.(2) C(B)-C(8B)-C(1B) 118.(2) C(B)-C(8B)-C(9B) 12.8(2) C(1B)-C(8B)-C(9B) 11.8(2) (B)-C(9B)-C(8B) 12.(2) (B)-C(9B)-C(10B) 11.(2) C(8B)-C(9B)-C(10B) 119.1(2) (B)-C(10B)-C(11B) 12.() (B)-C(10B)-C(9B) 11.(2) C(11B)-C(10B)-C(9B) 119.0(2) (B)-C(11B)-C(12B) 11.0(2) (B)-C(11B)-C(10B) 12.9(2) C(12B)-C(11B)-C(10B) 120.1() (B)-C(12B)-C(11B) 118.9() (B)-C(12B)-C(1B) 118.(2) C(11B)-C(12B)-C(1B) 122.(2) (2B)-C(1B)-C(8B) 122.2(2) (2B)-C(1B)-C(12B) 11.(2) C(8B)-C(1B)-C(12B) 121.(2) (B)-C(1B)-H(1D) 109. (B)-C(1B)-H(1E) 109. H(1D)-C(1B)-H(1E) 109. (B)-C(1B)-H(1F) 109. H(1D)-C(1B)-H(1F) 109. H(1E)-C(1B)-H(1F) 109. C(1B)-C(1B)-C(20B) 11.() C(1B)-C(1B)-C(2B) 122.(2) C(20B)-C(1B)-C(2B) 120.2(2) C(1B)-C(1B)-C(1B) 121.() C(1B)-C(1B)-H(1B) 119.2 C(1B)-C(1B)-H(1B) 119.2 C(18B)-C(1B)-C(1B) 120.2() C(18B)-C(1B)-H(1B) 119.9 C(1B)-C(1B)-H(1B) 119.9 C(1B)-C(18B)-C(19B) 119.0() C(1B)-C(18B)-H(18B) 120. C(19B)-C(18B)-H(18B) 120. C(20B)-C(19B)-C(18B) 120.() C(20B)-C(19B)-H(19B) 119.8 C(18B)-C(19B)-H(19B) 119.8 C(19B)-C(20B)-C(1B) 121.()
C(19B)-C(20B)-H(20B) 119. C(1B)-C(20B)-H(20B) 119. C(B)-C(21B)-C(22B) 11.(2) C(B)-C(21B)-H(21C) 108.2 C(22B)-C(21B)-H(21C) 108.2 C(B)-C(21B)-H(21D) 108.2 C(22B)-C(21B)-H(21D) 108.2 H(21C)-C(21B)-H(21D) 10. C(2B)-C(22B)-C(21B) 11.() C(2B)-C(22B)-H(22C) 108.9 C(21B)-C(22B)-H(22C) 108.9 C(2B)-C(22B)-H(22D) 108.9 C(21B)-C(22B)-H(22D) 108.9 H(22C)-C(22B)-H(22D) 10. C(2B)-C(2B)-C(22B) 128.() C(2B)-C(2B)-H(2B) 11.8 C(22B)-C(2B)-H(2B) 11.8 C(2B)-C(2B)-C(2B) 12.() C(2B)-C(2B)-C(2B) 121.() C(2B)-C(2B)-C(2B) 11.2() C(2B)-C(2B)-H(2D) 109. C(2B)-C(2B)-H(2E) 109. H(2D)-C(2B)-H(2E) 109. C(2B)-C(2B)-H(2F) 109. H(2D)-C(2B)-H(2F) 109. H(2E)-C(2B)-H(2F) 109. C(2B)-C(2B)-H(2D) 109. C(2B)-C(2B)-H(2E) 109. H(2D)-C(2B)-H(2E) 109. C(2B)-C(2B)-H(2F) 109. H(2D)-C(2B)-H(2F) 109. H(2E)-C(2B)-H(2F) 109. Table S. Anisotropic displacement parameters (Å 2 x 10 ) for (+)-1 and ( )-1. The anisotropic displacement factor exponent takes the form: -2p 2 [h 2 a* 2 U 11 +... + 2 h k a* b* U 12 ] U 11 U 22 U U 2 U 1 U 12 C(1) 2(2) (2) (2) -2(1) 1(1) 1(1) (1) 2(1) (1) 1(1) -(1) 29(1) -9(1) C(2) 1(2) 2(2) (2) -2(1) 1(1) -2(1) (2) 1(1) 29(1) (1) -2(1) 2(1) -(1) () 1() 2(1) 10(2) -(1) 11(2) (2) C() (2) (2) (2) -10(1) 1(2) (2) C() (2) (2) 0(2) -(1) 22(2) (1) () 211() 1(2) 1() -(2) 10() (2) C() 2(2) 2(2) (2) -(2) (2) 10(2) () 12(2) 8(1) 11(2) -(1) 8(2) -8(1) C() 2(2) (2) 8(2) -(2) (2) 10(2) () 100(2) 2(1) 80(2) 1(1) 1(1) (1)
C() (2) (2) (2) 0(1) 9(1) -(1) C(8) 2(2) 28(1) 1(2) 1(1) 10(1) 1(1) C(9) (2) 29(2) 1(2) -1(1) 1(2) (1) C(10) 2(2) 2(2) 8(2) 2(2) (2) 1(2) C(11) 92() (2) 88() -(2) 9(2) (2) C(12) 8(2) 2(2) 1(2) -2(1) 0(2) (2) C(1) (2) 2(2) 0(2) 2(1) 10(1) -1(1) C(1) 112() () 110() 1(2) () 21(2) C(1) (2) (2) (2) -(1) (1) 0(1) C(1) (2) 8(2) 0(2) 8(2) 12(2) -(2) C(1) 101() () () 18(2) () 8(2) C(18) 90() 0() 8() -(2) -18() 2(2) C(19) (2) () 88() -2(2) (2) (2) C(20) 0(2) (2) (2) -10(2) 9(2) -2(2) C(21) 1(2) (2) 1(2) -9(2) 20(2) (2) C(22) 9(2) (2) 8(2) -(2) 18(2) 1(2) C(2) 8(2) 9(2) 8() -(2) 2(2) 9(2) C(2) 0(2) 10() 8() -1(2) 20(2) 12(2) C(2) 108() 10() 188() -10() 11() 1() C(2) 90() 19() 9() -9() 1() -() (1B) (1) (1) 8(1) -(1) (1) -10(1) C(1B) (2) (2) 0(2) -2(1) 1(1) -(1) (2B) 1(1) 28(1) 2(1) -1(1) 2(1) -8(1) C(2B) (2) 2(2) 8(2) -2(1) 1(1) -2(1) (B) 111(2) 22(1) 8(2) -2(1) (1) -1(1) C(B) 8(2) 0(2) 0(2) -8(1) 1(1) -1(1) (B) 1(2) (1) 118(2) -1(1) 10(2) 1(1) C(B) (2) 8(2) (2) -(1) 1(1) (1) (B) 19() 28(1) 1(2) (1) 121(2) -(1) C(B) (2) 2(2) 2(2) -(2) 11(2) (1) (B) 98(2) 2(1) (2) 1(1) (1) 2(1) C(B) 0(2) 1(2) 1(2) -(1) (1) 1(1) C(B) 0(2) (2) 8(2) -2(1) 8(1) -(1) C(8B) 2(2) 2(1) (2) 0(1) 1(1) -1(1) C(9B) (2) 2(2) 2(2) 1(1) 1(1) 0(1) C(10B) 9(2) 2(2) 8(2) (1) (2) 0(1) C(11B) 8(2) 28(2) (2) -2(1) (2) 1(1) C(12B) 1(2) 2(2) 1(2) -1(1) 2(2) -1(1) C(1B) (2) 2(1) (2) (1) 1(1) -1(1) C(1B) 9() (2) (2) (2) (2) (2) C(1B) (2) 0(1) 0(2) -(1) 1(1) -1(1) C(1B) (2) 8(2) 1(2) 0(1) 11(1) -1(1) C(1B) 0(2) 2(2) (2) -(2) 19(2) 2(2) C(18B) (2) 2(2) 2(2) 1(2) 9(2) 1(2) C(19B) (2) (2) (2) 12(2) 1(2) 18(2) C(20B) 9(2) (2) 2(2) (1) 20(2) 2(2) C(21B) (2) (2) 9(2) -9(1) 1(2) (2) C(22B) 0(2) 1(2) (2) -(2) 18(2) 18(2) C(2B) 2(2) (2) (2) -2(2) 29(2) 1(2) C(2B) 0(2) 10() (2) -1(2) 19(2) 1(2) C(2B) 129() 222() 10() -2() 2() -() C(2B) 9() 1() 10() -0() 2() ()
Table S. Hydrogen coordinates (x 10 ) and isotropic displacement parameters (Å 2 x 10 ) for (+)-1 and ( )-1. x y z U(eq) H(1) -1221 9 2 H(1) 2 88 8 81 H(2) 828 88 H(1) 8 18 H(A) 218-2811 12 H(B) -2028 12 H() 0-028 H(A) 9 189 8 8 H(B) 280-1192 92 8 H(1A) 00 02 1 11 H(1B) 82 0 11 H(1C) 828 991 81 11 H(1) 20 18 28 81 H(1) 9 22 2 10 H(18) 0 1 298 10 H(19) 1 1 92 H(20) - 822 H(21A) 290-8 219 H(21B) 9-02 11 H(22A) 81-99 8 H(22B) 8-80 2 H(2) 821-8 89 82 H(2A) 80-988 20 2 H(2B) 80-100 22 2 H(2C) 81-982 1 2 H(2A) 81-281 209 180 H(2B) 8-00 180 H(2C) 829-0 122 180 H(1B) 89-9 8 8 H(1B) 8 12 8 H(2B) 881 288 8 H(B) 922-282 98 H(BA) 8 8 89 H(BB) 888 9 H(B) 2 09 1 1 H(BA) 0 0 12 8 H(BB) 8 092 8 H(1D) 1022 829 9 98 H(1E) 1020 29 99 98 H(1F) 91 2229 98 H(1B) 920 202 09 1 H(1B) 10 1 2 H(18B) 1080 1991 29 8 H(19B) 1000 111 1 H(20B) 9108 1882 21 8 H(21C) 812 902
H(21D) 8 89 828 H(22C) 22 921 80 H(22D) 910 800 18 H(2B) 1190 28 80 H(2D) 8 1009 20 21 H(2E) 2 8 89 21 H(2F) 18 10221 92 21 H(2D) 0 118 290 18 H(2E) 18 81 18 H(2F) 0 108 9 18 Table S. Torsion angles [ ] for (+)-1 and ( )-1. C()-C(1)-C(2)-C(1) -.8() C()-C(1)-C(2)-C(1) -18.(2) C()-C(1)-C(2)-C() -1.(2) C()-C(1)-C(2)-C().9() C(1)-C(2)-C()-C() -1.(2) C(1)-C(2)-C()-C() -0.() C(2)-C()-C()-C() 1.0() C(2)-C()-C()-C(21) -1.(2) C()-C()-C()-C().2() C(21)-C()-C()-C() -1.() C()-C()-C()-C(1) 12.0() C()-C(1)-C()-C() -19.8(2) C(2)-C(1)-C()-C() -.9() C()-C(1)-C()-(1) 8.() C(2)-C(1)-C()-(1) -1.9() C()-C(1)-C()-C(8) -101.() C(2)-C(1)-C()-C(8) 18.2() (1)-C()-C(8)-C(1).() C(1)-C()-C(8)-C(1) -1.9(2) (1)-C()-C(8)-C(9) -18.(2) C(1)-C()-C(8)-C(9) 1.() C()-C(8)-C(9)-() 9.1() C(1)-C(8)-C(9)-() -12.() C()-C(8)-C(9)-C(10) -12.(2) C(1)-C(8)-C(9)-C(10).8() ()-C(9)-C(10)-() -8.9() C(8)-C(9)-C(10)-() 12.() ()-C(9)-C(10)-C(11) 10.8() C(8)-C(9)-C(10)-C(11) -.() C(1)-()-C(11)-C(12).1() C(1)-()-C(11)-C(10) -12.1() ()-C(10)-C(11)-().1() C(9)-C(10)-C(11)-() -1.() ()-C(10)-C(11)-C(12) -1.2() C(9)-C(10)-C(11)-C(12).1() ()-C(11)-C(12)-() -0.2() C(10)-C(11)-C(12)-() 19.0()
()-C(11)-C(12)-C(1) 19.8() C(10)-C(11)-C(12)-C(1) -1.0() C()-C(8)-C(1)-(2) -.() C(9)-C(8)-C(1)-(2) 1.8(2) C()-C(8)-C(1)-C(12) 1.(2) C(9)-C(8)-C(1)-C(12) -1.9() ()-C(12)-C(1)-(2) -0.() C(11)-C(12)-C(1)-(2) 19.() ()-C(12)-C(1)-C(8) 19.() C(11)-C(12)-C(1)-C(8) -0.() C()-C(2)-C(1)-C(20) 91.() C(1)-C(2)-C(1)-C(20) -1.2() C()-C(2)-C(1)-C(1) -89.() C(1)-C(2)-C(1)-C(1) 1.() C(20)-C(1)-C(1)-C(1) -0.2() C(2)-C(1)-C(1)-C(1) -19.0() C(1)-C(1)-C(1)-C(18) 1.() C(1)-C(1)-C(18)-C(19) -1.2() C(1)-C(18)-C(19)-C(20) -0.1() C(18)-C(19)-C(20)-C(1) 1.2() C(1)-C(1)-C(20)-C(19) -1.0() C(2)-C(1)-C(20)-C(19) 1.() C()-C()-C(21)-C(22) -.2() C()-C()-C(21)-C(22) 1.() C()-C(21)-C(22)-C(2) 11.() C(21)-C(22)-C(2)-C(2) 8.2() C(22)-C(2)-C(2)-C(2) -0.() C(22)-C(2)-C(2)-C(2) 19.0() C(B)-C(1B)-C(2B)-C(1B) 2.() C(B)-C(1B)-C(2B)-C(1B) 1.(2) C(B)-C(1B)-C(2B)-C(B) 1.9(2) C(B)-C(1B)-C(2B)-C(B) -2.9() C(1B)-C(2B)-C(B)-C(B) 12.(2) C(1B)-C(2B)-C(B)-C(B).() C(2B)-C(B)-C(B)-C(B) -1.() C(2B)-C(B)-C(B)-C(21B) 1.(2) C(B)-C(B)-C(B)-C(B) -2.() C(21B)-C(B)-C(B)-C(B) 1.9() C(B)-C(B)-C(B)-C(1B) -1.0() C(B)-C(1B)-C(B)-C(B) 10.(2) C(2B)-C(1B)-C(B)-C(B).() C(B)-C(1B)-C(B)-(1B) -2.() C(2B)-C(1B)-C(B)-(1B) 8.8() C(B)-C(1B)-C(B)-C(8B) 10.() C(2B)-C(1B)-C(B)-C(8B) -12.1() (1B)-C(B)-C(8B)-C(1B) -2.() C(1B)-C(B)-C(8B)-C(1B) 18.(2) (1B)-C(B)-C(8B)-C(9B) 19.8(2) C(1B)-C(B)-C(8B)-C(9B) 0.8() C(B)-C(8B)-C(9B)-(B) -.8() C(1B)-C(8B)-C(9B)-(B) 1.() C(B)-C(8B)-C(9B)-C(10B) 1.2(2)
C(1B)-C(8B)-C(9B)-C(10B) -2.() (B)-C(9B)-C(10B)-(B) 1.0() C(8B)-C(9B)-C(10B)-(B) -19.9() (B)-C(9B)-C(10B)-C(11B) -19.() C(8B)-C(9B)-C(10B)-C(11B) -0.() C(1B)-(B)-C(11B)-C(12B) 11.() C(1B)-(B)-C(11B)-C(10B) -10.8() (B)-C(10B)-C(11B)-(B).0() C(9B)-C(10B)-C(11B)-(B) -1.() (B)-C(10B)-C(11B)-C(12B) -18.2() C(9B)-C(10B)-C(11B)-C(12B) 2.() (B)-C(11B)-C(12B)-(B) -1.9() C(10B)-C(11B)-C(12B)-(B) -19.8() (B)-C(11B)-C(12B)-C(1B) 1.() C(10B)-C(11B)-C(12B)-C(1B) -1.() C(B)-C(8B)-C(1B)-(2B).() C(9B)-C(8B)-C(1B)-(2B) -1.9(2) C(B)-C(8B)-C(1B)-C(12B) -1.(2) C(9B)-C(8B)-C(1B)-C(12B).() (B)-C(12B)-C(1B)-(2B) -1.9() C(11B)-C(12B)-C(1B)-(2B) 19.() (B)-C(12B)-C(1B)-C(8B) 1.9(2) C(11B)-C(12B)-C(1B)-C(8B) -1.() C(B)-C(2B)-C(1B)-C(1B) -8.8() C(1B)-C(2B)-C(1B)-C(1B).() C(B)-C(2B)-C(1B)-C(20B) 89.8() C(1B)-C(2B)-C(1B)-C(20B) -18.1(2) C(20B)-C(1B)-C(1B)-C(1B) -1.1() C(2B)-C(1B)-C(1B)-C(1B) 1.(2) C(1B)-C(1B)-C(1B)-C(18B) -0.() C(1B)-C(1B)-C(18B)-C(19B) 1.8() C(1B)-C(18B)-C(19B)-C(20B) -1.2() C(18B)-C(19B)-C(20B)-C(1B) -0.() C(1B)-C(1B)-C(20B)-C(19B) 1.() C(2B)-C(1B)-C(20B)-C(19B) -1.1() C(B)-C(B)-C(21B)-C(22B) -2.0() C(B)-C(B)-C(21B)-C(22B) 1.() C(B)-C(21B)-C(22B)-C(2B) -18.9() C(21B)-C(22B)-C(2B)-C(2B) -9.() C(22B)-C(2B)-C(2B)-C(2B) -0.() C(22B)-C(2B)-C(2B)-C(2B) 19.()
Table S. Hydrogen bonds for (+)-1 and ( )-1 [Å and ]. D-H...A d(d-h) d(h...a) d(d...a) <(DHA) C(1)-H(1)...() 1.00 2.21 2.891() 12. (1)-H(1)...(2) 0.8 1.9 2.8() 10. ()-H(1)...(2) 0.8 2.1 2.0() 11. ()-H(1)...()#1 0.8 1.9 2.2() 1.8 C(1)-H(1A)...() 0.98 2.1 2.8() 9. (1B)-H(1B)...(2B) 0.8 1.9 2.() 10.2 C(1B)-H(1B)...(B) 1.00 2.1 2.902() 129. (B)-H(B)...(2B) 0.8 2.21 2.9() 11.2 (B)-H(B)...(B)#2 0.8 1.98 2.8() 18.9 Symmetry transformations used to generate equivalent atoms: #1 x,y+1,z #2 x,y-1,z
S. (a) Superposed experimental ECD spectrum of (+)-ecarlottone (black) with the computed ECD spectrum (red) starting from the X-ray structure of 1 (S,S); (b) X-ray structure of 1 (S,S); (c) Superposed experimental ECD spectrum of ( )-ecarlottone (black) with the computed ECD spectrum (red) starting from the X-ray structure of 1 (R,R); (d) X-ray structure of 1 (R,R). a b c d
S8. 1 H NMR (00 MHz, CDCl at 2 K) spectrum of compound,0 1,0,0 0 20 0 0 80 100 120 10 10,0 1,0 1,0 ppm,,28,18,1,9,0,2,,,110,9,0,0,00,01 2,901 2,89 2,8 2,80,9,8,0,2,,. (dd, J= 12.9Hz,.Hz) 1 1 1 1 1,0,,,,,,2-2 0 2 8 10 12 1 1 18 20 ppm,0,0,00,01 1,0 % 8 8a a 1' 2 2' ' ' ' ppm,2,1,1.0 (dd, J= 1.Hz, 12.9Hz) 1 1 1 1,0 2,9 2,901 2,89 2,8 2,80 2.88 (dd, J= 1.Hz,.Hz) 1 1 1 1 1,0 2,9 2,8 2,8 2, 2, % ppm,8,,,2,8,,,2,8,,,2,8,,,2,8,,,2 2,8 2, 2, 2,2
S9. 1 H NMR (00 MHz, CDCl ) spectrum of the new compound 11 12 10 8 9 2'' 1'' 2 ' ' ' 1 1' 2' '
S10. 1 C NMR ( MHz, CDCl ) spectrum of the new compound 0 10 20 0 0 0 0 0 80 90 100 110 ppm 212,9 2'' 1'' 2 ' ' 11 12 10 9 8 1 1' 2' ' ' 1,8 1, 11,89 128,8 12, 12,99 12,22 118,80,,,00,2 29,908 29,08 2,2 2,9 1,9 % ppm 210 200 190 180 10 10 10 10 10 120 110 100 90 80 0 0 0 0 0 20
S11. HSQC (00 MHz, CDCl ) spectrum of the new compound 10 1 CG1-1-8 18 (1D 1H) 100 20 0 80 % 11 12 10 8 9 0 2'' 1'' 2 ' ' ' 1 1' 2' ' 120 ppm ppm,,2,8,,,2,8,,,2,8,,,2,8,,,2 2,8 2, 2, 2,2 2 1,8 % 1, CG1-1-8 2 (1D 1C) 0 10010
120 100 80 0 0 20 0 S12. HMBC (00 MHz, CDCl ) spectrum of the new compound 10 20 0 0 CG1-1-8 18 (1D 1H) % 11 12 10 10 8 9 ppm 200 180 10 ppm,2,8 2'' 1'' 2 1 1' ' ' ',, 2' ',2,8,,,2,8,,,2,8,,,2 2,8 2, 2, 2,2 2 1,8 % 1, CG1-1-8 2 (1D 1C) 10 20 0
S1. 1H NMR (00 MHz, CDCl) spectrum of the new compound 12 10 9 11 8 2'' 1'' 2 1 1' ' 2' ' ' '
S1. 1 C NMR (1 MHz, CDCl ) spectrum of the new compound 12 9 10 11 8 2'' 1'' 2 ' 1 1' 2' ' ' '
S1. HSQC (00 MHz, CDCl ) spectrum of the new compound 20 0 0 80 CG1-1- 1 (1D 1H) 100 80 20 0 % 12 9 10 11 8 0 2'' 1'' 2 ' 1 1' 2' ' ' ' 120 ppm ppm,,,, 2, 2 1, CG1-1- (1D 1C) % 20 0 0 80
0 0 80 100 20 0 S1. HMBC (00 MHz, CDCl ) spectrum of the new compound 20 0 0 80 CG1-1- 1 (1D 1H) % 12 9 10 11 8 120 2'' 1'' 2 ' 1 1' 2' ppm 10 ppm, ' ' ',,, 2, 2 1, CG1-1- (1D 1C) % 20 0 0 80
S1. 1 H NMR (00 MHz, CDCl ) spectrum of the new compound 11 12 10 8 9 H 1'' 2 ' ' 1 1' ' 2' '
S18. 1 C NMR (1 MHz, CDCl ) spectrum of the new compound 0 10 20 0 0 0 0 0 80 90 100 110 ppm 19,01 Compound (DEPT 1C) Compound (1D 1C) H 1'' 2 ' ' 11 12 10 9 8 1 1' 2' ' ' 1,189 1, 11,918 128,90 12,90 12,81 12,18 118,88, 2,9,,9 29,8 2,21 2,92 1,9 % ppm 180 10 10 10 10 10 120 110 100 90 80 0 0 0 0 0 20
S19. HSQC (00 MHz, CDCl ) spectrum of the new compound % 200080100 CG1-1-1 1 (1D 1H) 20 11 12 10 8 9 0 0 H 1'' 2 ' ' 1 1' ' 2' ' 100 120 80 ppm ppm,,,, 2, 2 1, % Compound (1D 1C) 10 20 00
S20. HMBC (00 MHz, CDCl ) spectrum of the new compound 0 10010 CG1-1-1 1 (1D 1H) 10 120 100 0 20 % 11 12 10 8 9 0 80 H 1'' 2 ' ' ' 1 1' 2' ' ppm 180 10 ppm,,,, 2, 2 1, % Compound (1D 1C) 10 20 0
S21. Raw data used for Table and their graphical representation Bcl-xL/Bak Compound (+)-1 Concentration (nm) % inhib. (mean value) Bcl-xL/Bak Error Concentration (nm) % inhib. (mean value) Mcl-1/Bid 100000 2 1, 100000 92 0,8 000-9,0 000 2 0,9 11000-11,2 11000 8,0 00-1,9 00-8 2, 1200-11 0,9 1200-8,0 10-11 0, 10-8,0 10-11 1,2 10-1 1, -9 2,2-10 2, Error Mean value Error Mean value Error IC 0 (nm) ################## IC 0 (nm) 228 99 K i (nm) ################## K i (nm) 29 10 Compound ( )-1 Concentration (nm) Bcl-xL/Bak % inhib. (mean value) Bcl-xL/Bak Error Mcl-1/Bid Compound (+)-1 Mcl-1/Bid Compound ( )-1 Concentration (nm) % inhib. (mean value) Mcl-1/Bid 100000 88 0,8 100000 9,9 000 2 0,9 000 9 8,0 11000,0 11000 2,0 00 8 2, 00 1,0 1200 -,0 1200 1 0,8 10-8,0 10-0,9 10-10 1, 10-1 1, -10 2, 2 2, Error Mean value Error Mean value Error IC 0 (nm) 2080 IC 0 (nm) 28 99 K i (nm) 102 K i (nm) 21 12 Pourcentage of inhibition (%) Pourcentage of inhibition (%) Compound (+)-1 100 80 0 0 20 0 10 100 1000 10000 100000 1000000-20 Concentration (nm) Compound ( )-1 100 80 0 0 20 0 10 100 1000 10000 100000 1000000-20 Concentration (nm) Bcl-xL/Bak Mcl-1/Bid Mcl-1/Bid Bcl-xL/Bak