Supporting information. (+)- and ( )-Ecarlottones, Uncommon Chalconoids. from Fissistigma latifolium with Proapoptotic

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1 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, Gif-sur-Yvette Cedex, France. Department of Chemistry, Faculty of Science, University Malaya, Kuala Lumpur 00, Malaysia. Corresponding Author *Tel: +(0) Fax: +(0) vincent.dumontet@cnrs.fr (V. D.). *Tel: +(0) Fax: +(0) marc.litaudon@cnrs.fr (M. L.).

2 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

3 S1. 1 H NMR (00 MHz, CDCl ) spectra of the new compound 1 at various temperatures '' '' '' 8 9 H '' '' 2'' 2 1'' H ' 1 1' 2' 22 K ' ' ' 2 K 2 K 2 K 2 K 298 K

4 S2. 1 H NMR (00 MHz, CDCl at 2 K) spectrum of the new compound '' '' '' 8 9 H '' '' 2'' 2 1'' H ' 1 1' 2' ' ' '

5 S. 1 C NMR (10 MHz, CDCl at 2 K) spectrum of the new compound '' '' '' 8 9 H '' '' 2'' 2 1'' H ' 1 1' 2' ' ' '

6 S. HSQC (00 MHz, CDCl at 2 K) spectrum of the new compound '' '' '' 8 9 H '' '' 2'' 2 1'' H ' 1 1' 2' ' ' '

7 S. HMBC (00 MHz, CDCl at 2 K) spectrum of the new compound '' '' '' 8 9 H '' '' 2'' 2 1'' H ' 1 1' 2' ' ' '

8 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 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 and are available free of charge via 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, () 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.

9 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 Index ranges -21 h 29, -8 k 8, -2 l 0 Reflections collected 2198 Independent reflections 8181 [R(int) = 0.08] Completeness to theta = % 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 F Final R indices [I>2s(I)] R1 = 0.09, wr2 = 0.18 R indices (all data) R1 = 0.109, wr2 = Largest diff. peak and hole 0.2 and 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)

10 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)

11 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)-C() 1.1() (1)-H(1) C(2)-C(1) 1.01() C(2)-C() 1.0() C(2)-H(2) (2)-C(1) 1.2() ()-C(12) 1.() ()-H(1) C()-C() 1.0() C()-H(A) C()-H(B) C()-C() 1.1() C()-C(21) 1.1() ()-C(11) 1.1() ()-C(1) 1.2() C()-C() 1.99() C()-H() ()-C(10) 1.21() C()-H(A) C()-H(B) ()-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) C(1)-H(1B) C(1)-H(1C) C(1)-C(20) 1.80() C(1)-C(1) 1.02() C(1)-C(1) 1.() C(1)-H(1) C(1)-C(18) 1.9() C(1)-H(1) C(18)-C(19) 1.() C(18)-H(18) C(19)-C(20) 1.0() C(19)-H(19) C(20)-H(20) C(21)-C(22) 1.28() C(21)-H(21A) C(21)-H(21B)

12 C(22)-C(2) 1.8() C(22)-H(22A) C(22)-H(22B) C(2)-C(2) 1.299() C(2)-H(2) C(2)-C(2) 1.88() C(2)-C(2) 1.0() C(2)-H(2A) C(2)-H(2B) C(2)-H(2C) C(2)-H(2A) C(2)-H(2B) C(2)-H(2C) (1B)-C(B) 1.1() (1B)-H(1B) C(1B)-C(B) 1.99() C(1B)-C(B) 1.() C(1B)-C(2B) 1.0() C(1B)-H(1B) (2B)-C(1B) 1.2() C(2B)-C(1B) 1.11() C(2B)-C(B) 1.1() C(2B)-H(2B) (B)-C(12B) 1.() (B)-H(B) C(B)-C(B) 1.98() C(B)-H(BA) C(B)-H(BB) (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) (B)-C(9B) 1.21() C(B)-H(BA) C(B)-H(BB) 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) C(1B)-H(1E) C(1B)-H(1F) C(1B)-C(1B) 1.8() C(1B)-C(20B) 1.91() C(1B)-C(1B) 1.9() C(1B)-H(1B) 0.900

13 C(1B)-C(18B) 1.8() C(1B)-H(1B) C(18B)-C(19B) 1.8() C(18B)-H(18B) C(19B)-C(20B) 1.() C(19B)-H(19B) C(20B)-H(20B) C(21B)-C(22B) 1.28() C(21B)-H(21C) C(21B)-H(21D) C(22B)-C(2B) 1.0() C(22B)-H(22C) C(22B)-H(22D) C(2B)-C(2B) 1.0() C(2B)-H(2B) C(2B)-C(2B) 1.2() C(2B)-C(2B) 1.08() C(2B)-H(2D) C(2B)-H(2E) C(2B)-H(2F) C(2B)-H(2D) C(2B)-H(2E) C(2B)-H(2F) 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) C()-C(1)-H(1) C(2)-C(1)-H(1) 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) C(2)-C()-H(A) C()-C()-H(B) C(2)-C()-H(B) 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)

14 C()-C()-H(A) C(1)-C()-H(A) C()-C()-H(B) C(1)-C()-H(B) 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

15 C(22)-C(21)-H(21A) C()-C(21)-H(21B) C(22)-C(21)-H(21B) 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)

16 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) C(1B)-C(1B)-H(1B) C(18B)-C(1B)-C(1B) 120.2() C(18B)-C(1B)-H(1B) C(1B)-C(1B)-H(1B) 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) C(18B)-C(19B)-H(19B) C(19B)-C(20B)-C(1B) 121.()

17 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) C(22B)-C(21B)-H(21C) C(B)-C(21B)-H(21D) C(22B)-C(21B)-H(21D) H(21C)-C(21B)-H(21D) 10. C(2B)-C(22B)-C(21B) 11.() C(2B)-C(22B)-H(22C) C(21B)-C(22B)-H(22C) C(2B)-C(22B)-H(22D) C(21B)-C(22B)-H(22D) 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 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)

18 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() ()

19

20 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) H(1) H(2) H(1) 8 18 H(A) H(B) H() H(A) H(B) H(1A) H(1B) H(1C) H(1) H(1) H(18) H(19) H(20) H(21A) H(21B) H(22A) H(22B) H(2) H(2A) H(2B) H(2C) H(2A) H(2B) H(2C) H(1B) H(1B) H(2B) H(B) H(BA) H(BB) H(B) H(BA) H(BB) H(1D) H(1E) H(1F) H(1B) H(1B) H(18B) H(19B) H(20B) H(21C)

21 H(21D) H(22C) H(22D) H(2B) H(2D) H(2E) H(2F) H(2D) H(2E) H(2F) 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()

22 ()-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)

23 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.()

24 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)...() () 12. (1)-H(1)...(2) () 10. ()-H(1)...(2) () 11. ()-H(1)...()# () 1.8 C(1)-H(1A)...() () 9. (1B)-H(1B)...(2B) () 10.2 C(1B)-H(1B)...(B) () 129. (B)-H(B)...(2B) () 11.2 (B)-H(B)...(B)# () 18.9 Symmetry transformations used to generate equivalent atoms: #1 x,y+1,z #2 x,y-1,z

25 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

26 S8. 1 H NMR (00 MHz, CDCl at 2 K) spectrum of compound,0 1,0, ,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) ,0,,,,,, ppm,0,0,00,01 1,0 % 8 8a a 1' 2 2' ' ' ' ppm,2,1,1.0 (dd, J= 1.Hz, 12.9Hz) ,0 2,9 2,901 2,89 2,8 2, (dd, J= 1.Hz,.Hz) ,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

27 S9. 1 H NMR (00 MHz, CDCl ) spectrum of the new compound '' 1'' 2 ' ' ' 1 1' 2' '

28 S10. 1 C NMR ( MHz, CDCl ) spectrum of the new compound ppm 212,9 2'' 1'' 2 ' ' ' 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

29 S11. HSQC (00 MHz, CDCl ) spectrum of the new compound 10 1 CG (1D 1H) % '' 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, CG (1D 1C)

30 S12. HMBC (00 MHz, CDCl ) spectrum of the new compound CG (1D 1H) % ppm 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, CG (1D 1C)

31 S1. 1H NMR (00 MHz, CDCl) spectrum of the new compound '' 1'' 2 1 1' ' 2' ' ' '

32 S1. 1 C NMR (1 MHz, CDCl ) spectrum of the new compound '' 1'' 2 ' 1 1' 2' ' ' '

33 S1. HSQC (00 MHz, CDCl ) spectrum of the new compound CG (1D 1H) % '' 1'' 2 ' 1 1' 2' ' ' ' 120 ppm ppm,,,, 2, 2 1, CG1-1- (1D 1C) %

34 S1. HMBC (00 MHz, CDCl ) spectrum of the new compound CG (1D 1H) % '' 1'' 2 ' 1 1' 2' ppm 10 ppm, ' ' ',,, 2, 2 1, CG1-1- (1D 1C) %

35 S1. 1 H NMR (00 MHz, CDCl ) spectrum of the new compound H 1'' 2 ' ' 1 1' ' 2' '

36 S18. 1 C NMR (1 MHz, CDCl ) spectrum of the new compound ppm 19,01 Compound (DEPT 1C) Compound (1D 1C) H 1'' 2 ' ' ' 2' ' ' 1,189 1, 11, ,90 12,90 12,81 12,18 118,88, 2,9,,9 29,8 2,21 2,92 1,9 % ppm

37 S19. HSQC (00 MHz, CDCl ) spectrum of the new compound % CG (1D 1H) H 1'' 2 ' ' 1 1' ' 2' ' ppm ppm,,,, 2, 2 1, % Compound (1D 1C)

38 S20. HMBC (00 MHz, CDCl ) spectrum of the new compound CG (1D 1H) % H 1'' 2 ' ' ' 1 1' 2' ' ppm ppm,,,, 2, 2 1, % Compound (1D 1C)

39 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 , , , , , ,0 00-1, , , , , 10-8, , , -9 2,2-10 2, Error Mean value Error Mean value Error IC 0 (nm) ################## IC 0 (nm) K i (nm) ################## K i (nm) 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 , , , , , , , 00 1, , ,8 10-8,0 10-0, , , -10 2, 2 2, Error Mean value Error Mean value Error IC 0 (nm) 2080 IC 0 (nm) K i (nm) 102 K i (nm) Pourcentage of inhibition (%) Pourcentage of inhibition (%) Compound (+) Concentration (nm) Compound ( ) Concentration (nm) Bcl-xL/Bak Mcl-1/Bid Mcl-1/Bid Bcl-xL/Bak