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1 Supplementary Information Cytotoxicity, Hemolytic Toxicity and Mechanism of Action of Pulsatilla Saponin D and Its Synthetic Derivatives Zhong Chen a,b, Huaqing Duan a, Xiaohang Tong a, Peiling Hsu b, Li Han c, Susan L. Morris-Natschke b, Shilin Yang a, Wei Liu b,d *, Kuo-Hsiung Lee b * a College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou , China b Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA c Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, 80 Chang Jiang Road, Nanyang , China d Department of Pharmacology, Nanjing Medical University, Nanjing, 21029, China Corresponding Author *Tel (K.H. Lee): Fax: khlee@unc.edu. *Tel (W. Liu): Fax: address:liuweicp@njmu.edu.cn 1

2 List of Figures Figure S1. 1 H NMR spectra of compound 2 Figure S2. 13 C NMR spectra of compound 2 Figure S3. 1 H NMR spectra of compound 3 Figure S4. 13 C NMR spectra of compound 3 Figure S5. 1 H NMR spectra of compound 4 Figure S6. 13 C NMR spectra of compound 4 Figure S7. 1 H NMR spectra of compound 5 Figure S8. 13 C NMR spectra of compound 5 Figure S9. 1 H NMR spectra of compound 6 Figure S C NMR spectra of compound 6 Figure S11. 1 H NMR spectra of compound 7 Figure S C NMR spectra of compound 7 Figure S13. 1 H NMR spectra of compound 8 Figure S C NMR spectra of compound 8 Figure S15. 1 H NMR spectra of compound 9 Figure S C NMR spectra of compound 9 Figure S17. 1 H NMR spectra of compound 10 Figure S C NMR spectra of compound 10 Figure S19. 1 H NMR spectra of compound 11 Figure S C NMR spectra of compound 11 Figure S21. 1 H NMR spectra of compound 12 Figure S CNMR spectra of compound 12 Figure S23. 1 H NMR spectra of compound 13 Figure S C NMR spectra of compound 13 Figure S25. 1 H NMR spectra of compound 14 Figure S C NMR spectra of compound 14 Figure S27. 1 H NMR spectra of compound 15 Figure S C NMR spectra of compound 15 2

3 Figure S29. 1 H NMR spectra of compound 16 Figure S C NMR spectra of compound 16 Figure S31. 1 H NMR spectra of compound 17 Figure S C NMR spectra of compound 17 Figure S33. 1 H NMR spectra of compound 18 Figure S C NMR spectra of compound 18 3

4 Figure S1. 1 H NMR spectra of compound 2 Figure S2. 13 CNMR spectra of compound 2 4

5 Figure S3. 1 H NMR spectra of compound 3 Figure S4. 13 CNMR spectra of compound 3 5

6 Figure S5. 1 H NMR spectra of compound 4 Figure S6. 13 CNMR spectra of compound 4 6

7 Figure S7. 1 H NMR spectra of compound 5 Figure S8. 13 CNMR spectra of compound 5 7

8 Figure S9. 1 H NMR spectra of compound 6 Figure S CNMR spectra of compound 6 8

9 Figure S11. 1 H NMR spectra of compound 7 Figure S CNMR spectra of compound 7 9

10 Figure S13. 1 H NMR spectra of compound 8 Figure S CNMR spectra of compound 8 10

11 Figure S15. 1 H NMR spectra of compound 9 Figure S CNMR spectra of compound 9 11

12 Figure S17. 1 H NMR spectra of compound 10 Figure S CNMR spectra of compound 10 12

13 Figure S19. 1 H NMR spectra of compound 11 Figure S CNMR spectra of compound 11 13

14 Figure S21. 1 H NMR spectra of compound 12 Figure S CNMR spectra of compound 12 14

15 Figure S23. 1 H NMR spectra of compound 13 Figure S CNMR spectra of compound 13 15

16 Figure S25. 1 H NMR spectra of compound 14 Figure S CNMR spectra of compound 14 16

17 Figure S27. 1 H NMR spectra of compound 15 Figure S CNMR spectra of compound 15 17

18 Figure S29. 1 H NMR spectra of compound 16 Figure S CNMR spectra of compound 16 18

19 Figure S31. 1 H NMR spectra of compound 17 Figure S CNMR spectra of compound 17 19

20 Figure S33. 1 H NMR spectra of compound 18 Figure S CNMR spectra of compound 18 20

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