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1 Supporting Information Galanthamine, Plicamine, and Secoplicamine Alkaloids from Zephyranthes candida and Their Anti-acetylcholinesterase and Anti-inflammatory Activities Guanqun Zhan, Junfei Zhou, Rong Liu, Tingting Liu, Guoli Guo, Jianping Wang, Ming Xiang, Yongbo Xue, Zengwei Luo, Yonghui Zhang, and Guangmin Yao * Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan , People s Republic of China List of Supporting Information Table S1. 1 H NMR Data for Compounds 7 11 in Methanol-d 4 (400 MHz)... 6 Table S2. 13 C NMR Data for Compounds 7 11 in Methanol-d 4 (100 MHz)... 7 Table S3. 1 H NMR Data for Compounds in Methanol-d 4 (400 MHz)... 8 Table S4. 13 C NMR Data for Compounds in Methanol-d 4 (100 MHz)... 9 Table S5. AChE Inhibitory Activities of Alkaloids 1 24 a Table S6. Inhibitory Effects of Alkaloids 1 24 a on the LPS-Induced NO Production in RAW264.7 Mouse Macrophages and the Cell Survival Rate Extraction and Isolation Figure S1. Comparison of ECD spectra for 1 6 and 17 in MeOH Figure S2. Comparison of ECD spectra for 7 16 and 22 in MeOH Figure S3. Data fitting curves of the AChE inhibitory activities of compounds 3, 12 14, and Figure S4. Data fitting curves of the inhibitory effects of compounds 10 12, 14, 16, and dexamethasone on the LPS-induced NO production in RAW264.7 mouse macrophages Figure S5. (+)-HR-ESI-MS spectrum of Figure S6. UV spectrum of 1 in MeOH Figure S7. ECD spectrum of 1 in MeOH Figure S8. IR spectrum of Figure S9. 1 H NMR (400 MHz) spectrum of 1 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 1 in CD 3 OD Figure S11. DEPT 135 spectrum of 1 in CD 3 OD * To whom correspondence should be addressed. Tel: Fax: gyap@mail.hust.edu.cn. 1

2 Figure S12. HSQC spectrum of 1 in CD 3 OD Figure S13. HMBC spectrum of 1 in CD 3 OD Figure S14. 1 H- 1 H COSY spectrum of 1 in CD 3 OD Figure S15. NOESY spectrum of 1 in CD 3 OD Figure S16. (+)-HR-ESI-MS spectrum of Figure S17. UV spectrum of 2 in MeOH Figure S18. ECD spectrum of 2 in MeOH Figure S19. IR spectrum of Figure S20. 1 H NMR (400 MHz) spectrum of 2 in CD 3 OD Figure S C NMR (00 MHz) spectrumof 2 in CD 3 OD Figure S22. DEPT 135 spectrum of 2 in CD 3 OD Figure S23. HSQC spectrum of 2 in CD 3 OD Figure S24. HMBC spectrum of 2 in CD 3 OD Figure S25. 1 H- 1 H COSY spectrum of 2 in CD 3 OD Figure S26. NOESY spectrum of 2 in CD 3 OD Figure S27. (+)-HR-ESI-MS spectrum of Figure S28. UV spectrum of 3 in MeOH Figure S29. CD spectrum of 3 in MeOH Figure S30. IR spectrum of Figure S31. 1 H NMR (400 MHz) spectrum of 3 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 3 in CD 3 OD Figure S33. DEPT 135 spectrum of 3 in CD 3 OD Figure S34. HSQC spectrum of 3 in CD 3 OD Figure S35.HMBC spectrum of 3 in CD 3 OD Figure S36. 1 H- 1 H COSY spectrum of 3 in CD 3 OD Figure S37. NOESY spectrum of 3 in CD 3 OD Figure S38. (+)-HR-ESI-MS spectrum of Figure S39. UV spectrum of 4 in MeOH Figure S40. ECD spectrum of 4 in MeOH Figure S41. IR spectrum of Figure S42. 1 H NMR (400 MHz) spectrum of 4 in CD 3 OD Figure S C NMR (100 MHz) spectrumof 4 in CD 3 OD Figure S44. DEPT 135 spectrum of 4 in CD 3 OD Figure S45. HSQC spectrum of 4 in CD 3 OD Figure S46. HMBC spectrum of 4 in CD 3 OD Figure S47. 1 H- 1 H COSY spectrum of 4 in CD 3 OD Figure S48. NOESY spectrum of 4 in CD 3 OD Figure S49. (+)-HR-ESI-MS spectrum of Figure S50. UV spectrum of 5 in MeOH Figure S51. ECD spectrum of 5 in MeOH Figure S52. IR spectrum of Figure S53. 1 H NMR (400 MHz) spectrum of 5 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 5 in CD 3 OD Figure S55. DEPT 135 spectrum of 5 in CD 3 OD Figure S56. HSQC spectrum of 5 in CD 3 OD Figure S57.HMBC spectrum of 5 in CD 3 OD Figure S58. 1 H- 1 H COSY spectrum of 5 in CD 3 OD Figure S59. NOESY spectrum of 5 in CD 3 OD Figure S60. (+)-HR-ESI-MS spectrum of Figure S61. UV spectrum of 6 in MeOH Figure S62. ECD spectrum of 6 in MeOH Figure S63. IR spectrum of

3 Figure S64. 1 H NMR (400 MHz) spectrum of 6 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 6 in CD 3 OD Figure S66. DEPT 135 spectrum of 6 in CD 3 OD Figure S67. HSQC spectrum of 6 in CD 3 OD Figure S68. HMBC spectrum of 6 in CD 3 OD Figure S69. 1 H- 1 H COSY spectrum of 6 in CD 3 OD Figure S70. NOESY spectrum of 6 in CD 3 OD Figure S71. (+)-HR-ESI-MS spectrum of Figure S72. UV spectrum of 7 in MeOH Figure S73. ECD spectrum of 7 in MeOH Figure S74. IR spectrum of Figure S75. 1 H NMR (400 MHz) spectrum of 7 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 7 in CD 3 OD Figure S77. DEPT 135 spectrum of 7 in CD 3 OD Figure S78. HSQC spectrum of 7 in CD 3 OD Figure S79. HMBC spectrum of 7 in CD 3 OD Figure S80. 1 H- 1 H COSY spectrum of 7 in CD 3 OD Figure S81. NOESY spectrum of 7 in CD 3 OD Figure S82. (+)-HR-ESI-MS spectrum of Figure S83. UV spectrum of 8 in MeOH Figure S84. ECD spectrum of 8 in MeOH Figure S85. IR spectrum of Figure S86. 1 H NMR (400 MHz) spectrum of 8 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 8 in CD 3 OD Figure S88. DEPT 135 spectrum of 8 in CD 3 OD Figure S89. HSQC spectrum of 8 in CD 3 OD Figure S90. HMBC spectrum of 8 in CD 3 OD Figure S91. 1 H- 1 H COSY spectrum of 8 in CD 3 OD Figure S92. NOESY spectrum of 8 in CD 3 OD Figure S93. (+)-HR-ESI-MS spectrum of Figure S94. UV spectrum of 9 in MeOH Figure S95. ECD spectrum of 9 in MeOH Figure S96. IR spectrum of Figure S97. 1 H NMR (400 MHz) spectrum of 9 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 9 in CD 3 OD Figure S99. DEPT 135 spectrum of 9 in CD 3 OD Figure S100. HSQC spectrum of 9 in CD 3 OD Figure S101. HMBC spectrum of 9 in CD 3 OD Figure S H- 1 H COSY spectrum of 9 in CD 3 OD Figure S103. NOESY spectrum of 9 in CD 3 OD Figure S104. (+)-HR-ESI-MS spectrum of Figure S105. UV spectrum of 10 in MeOH Figure S106. ECD spectrum of 10 in MeOH Figure S107. IR spectrum of Figure S H NMR (400 MHz) spectrum of 10 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 10 in CD 3 OD Figure S110. DEPT 135 spectrum of 10 in CD 3 OD Figure S111. HSQC spectrum of 10 in CD 3 OD Figure S112.HMBC spectrum of 10 in CD 3 OD Figure S H- 1 H COSY spectrum of 10 in CD 3 OD Figure S114. NOESY spectrum of 10 in CD 3 OD Figure S115. (+)-HR-ESI-MS spectrum of

4 Figure S116. UV spectrum of 11 in MeOH Figure S117. ECD spectrum of 11 in MeOH Figure S118. IR spectrum of Figure S H NMR (400 MHz) spectrum of 11 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 11 in CD 3 OD Figure S121. DEPT 135 spectrum of 11 in CD 3 OD Figure S122. HSQC spectrum of 11 in CD 3 OD Figure S123. HMBC spectrum of 11 in CD 3 OD Figure S H- 1 H COSY spectrum of 11 in CD 3 OD Figure S125. NOESY spectrum of 11 in CD 3 OD Figure S126. (+)-HR-ESI-MS spectrum of Figure S127. UV spectrum of 12 in MeOH Figure S128. ECD spectrum of 12 in MeOH Figure S129. IR spectrum of Figure S H NMR (400 MHz) spectrum of 12 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 12 in CD 3 OD Figure S132. DEPT 135 spectrum of 12 in CD 3 OD Figure S133. HSQC spectrum of 12 in CD 3 OD Figure S134. HMBC spectrum of 12 in CD 3 OD Figure S H- 1 H COSY spectrum of 12 in CD 3 OD Figure S136. NOESY spectrum of 12 in CD 3 OD Figure S137. (+)-HR-ESI-MS spectrum of Figure S138. UV spectrum of 13 in MeOH Figure S139. ECD spectrum of 13 in MeOH Figure S140. IR spectrum of Figure S H NMR (400 MHz) spectrum of 13 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 13 in CD 3 OD Figure S143. DEPT 135 spectrum of 13 in CD 3 OD Figure S144. HSQC spectrum of 13 in CD 3 OD Figure S145. HMBC spectrum of 13 in CD 3 OD Figure S H- 1 H COSY spectrum of 13 in CD 3 OD Figure S147. NOESY spectrum of 13 in CD 3 OD Figure S148. (+)-HR-ESI-MS spectrum of Figure S149. UV spectrum of 14 in MeOH Figure S150. ECD spectrum of 14 in MeOH Figure S151. IR spectrum of Figure S H NMR (400 MHz) spectrum of 14 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 14 in CD 3 OD Figure S154. DEPT 135 spectrum of 14 in CD 3 OD Figure S155. HSQC spectrum of 14 in CD 3 OD Figure S156.HMBC spectrum of 14 in CD 3 OD Figure S H- 1 H COSY spectrum of 14 in CD 3 OD Figure S158. NOESY spectrum of 14 in CD 3 OD Figure S159. (+)-HR-ESI-MS spectrum of Figure S160. UV spectrum of 15 in MeOH Figure S161. ECD spectrum of 15 in MeOH Figure S162. IR spectrum of Figure S H NMR (400 MHz) spectrum of 15 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 15 in CD 3 OD Figure S165. DEPT 135 spectrum of 15 in CD 3 OD Figure S166. HSQC spectrum of 15 in CD 3 OD Figure S167. HMBC spectrum of 15 in CD 3 OD

5 Figure S H- 1 H COSY spectrum of 15 in CD 3 OD Figure S169. NOESY spectrum of 15 in CD 3 OD Figure S170. (+)-HR-ESI-MS spectrum of Figure S171. UV spectrum of 16 in MeOH Figure S172. ECD spectrum of 16 in MeOH Figure S173. IR spectrum of Figure S H NMR (400 MHz) spectrum of 16 in CD 3 OD Figure S C NMR (100 MHz) spectrum of 16 in CD 3 OD Figure S176. DEPT 135 spectrum of 16 in CD 3 OD Figure S177. HSQC spectrum of 16 in CD 3 OD Figure S178.HMBC spectrum of 16 in CD 3 OD Figure S H- 1 H COSY spectrum of 16 in CD 3 OD Figure S180. NOESY spectrum of 16 in CD 3 OD

6 Table S1. 1 H NMR Data for Compounds 7 11 in Methanol-d 4 (400 MHz) position , d (9.9) 5.92, d (9.8) 5.91, d (9.9) 5.95, d (9.9) 5.80, d (9.9) , dd (9.9, 5.1) 6.11, dd (9.8, 5.2) 6.13, dd (9.9, 5.1) 6.12, dd (9.9, 5.1) 6.07, dd (9.9, 5.2) , ddd (5.1, 3.9, 3.4) 3.95, ddd (5.2, 3.6, 3.3) 3.95, ddd, (5.1, 4.2, 3.6) 3.96, ddd, (5.1, 4.0, 3.2) 3.92, ddd (5.2, 3.6, 3.3) 4α 1.62, overlap 1.58, overlap 1.62, ddd, (13.4, 11.7, 1.62, ddd, (13.5, 11.6, 1.58, ddd, (13.5, 11.6, 3.6) 3.2) 3.3) 4β 2.44, ddd, (13.4, 4.6, 2.45, ddd, (13.4, 4.6, 3.6) 2.44, ddd, (13.4, 4.6, 4.2) 2.45, ddd, (13.5, 4.6, 2.41, ddd, (13.5, 4.5, 3.6) 3.9) 4.0) 4a 3.77, dd, (11.5, 4.6) 3.78, dd (11.5, 4.6) 3.77, dd, (11.7, 4.6) 3.78, dd, (11.6, 4.6) 3.76, dd, (11.6, 4.5) 6α 3.80, d, (15.3) 3.79, d, (15.2) 3.79, d, (15.3) 3.79, d, (15.3) 3.83, d, (15.3) 6β 3.66, d, (15.3) 3.60, d, (15.2) 3.65, d, (15.3) 3.69, d, (15.3) 3.73, d, (15.3) , s 6.50, s 6.52, s 6.52, s 6.51, s , s 6.74, s 6.76, s 6.75, s 6.74, s , s 3.65, s 3.71, s 3.74, s 3.72, s OCH 2 O 5.89, d, (0.9); 5.87, d, (0.9) 5.88, d, (0.9); 5.87, d, (0.9) 5.89, d, (0.9); 5.88, d, (0.9) 5.89, d, (0.9); 5.88, d, (0.9) 5.88, d, (1.0); 5.87, d, (1.0) OCH , s 3.48, s 3.48, s 3.48, s 3.47, s NCH , s 2.70, s 2.72, s 2.72, s 2.70, s , m 2.93, dd, (12.9, 6.2); 2.71, 2.99, m 3.08, t, (6.8) 3.26, m overlap , m 1.60, overlap 1.52, m 1.84, m 2.83, m , overlap 1.46, m; 1.12, m 1.32, overlap 2.34, t, (7.2) , d, (6.5) 0.91, t, (7.4) 1.32, overlap 7.21, overlap , d, (6.5) 0.89, d, (6.5) 1.32, overlap 7.21, overlap , t, (6.9) 7.14, m , overlap , overlap 6

7 Table S2. 13 C NMR Data for Compounds 7 11 in Methanol-d 4 (100 MHz) position a a a b OCH 2 O OCH NCH

8 Table S3. 1 H NMR Data for Compounds in Methanol-d 4 (400 MHz) position , d (9.9) 5.86, ddd (10.6, 2.0, 1.8) 5.82, ddd (10.5, 2.0, 5.67, d (9.9) 5.67, d (9.9) 1.8) , dd (9.9, 5.1) 5.77, br, d (10.6) 5.74, br d (10.5) 6.30, dd (9.9, 5.1) 6.30, dd (9.9, 5.1) , ddd (5.1, 4.0, 3.3) 3.78, m 3.77, m 4.08, ddd (5.1, 4.0, 2.3) 4.09, ddd, (5.1, 4.0, 2.2) 4α 1.57, ddd, (13.5, 11.6, 2.04, ddd, (14.5, 10.2, 2.04, ddd, (14.3, 10.1, 2.68, ddd, (13.3, 13.1, 2.70, ddd, (13.3, 13.0, 4.0) 3.3) 2.0) 2.1) 4.0) 4β 2.40, ddd, (13.5, 4.5, 4.0) 2.81, ddd, (14.5, 4.8, 2.8) 2.81, overlap 1.98, ddd, (13.3, 2.7, 2.3) 2.00, ddd, (13.3, 2.8, 2.2) 4a 3.75, dd, (11.6, 4.5) 3.94, overlap 3.94, overlap 3.91, dd, (13.1, 2.7) 3.92, dd, (13.0, 2.8) 6α 3.87, d, (15.3) 4.27, d, (15.9) 4.30, d, (15.8) 4.37, d, (16.8) 4.42, d, (16.8) 6β 3.77, d, (15.3) 3.46, d, (15.9) 3.66, d, (15.8) 4.29, d, (16.8) 4.26, d, (16.8) , s 6.63, s 6.65, s 6.64, s 6.70, s , s 6.76, s 6.76, s 6.69, s 6.70, s , s 7.18, s , s 3.14, s 3.26, s OCH 2 O 5.89, d, (1.0); 5.88, d, 5.90, d, (0.9); 5.89, d, 5.90, d, (1.0); 5.89, d, 5.99, d, (1.0); 5.98, d, 5.99, d, (0.9); 5.98, d, (0.9) (1.0) (0.9) (1.0) (1.0) OCH , s 3.43, s 3.42, s 3.47, s 3.46, s NCH , s 2.86, s 2.85, s 2.70, s 2.64, s 13a 3.40, overlap 3.93, overlap 3.88, overlap 3.05, s 3.75, ddd, (13.1, 10.0, 6.1) 13b 3.30, overlap 2.38, ddd, (12.3, 8.9, 4.5) 2.74, overlap 3.19, ddd, (13.1,10.0, 5.4) , t, (7.5) 1.51, m; 1.41, m 2.77, overlap 1.49, m , m 1.59, m , d, (6.5) 7.08, d, (8.5) 0.955, d, (6.4) , br d, (7.8) 0.94, d, (6.5) 6.70, d, (8.0) 0.950, d, (6.4) , ddd, (7.8, 7.1, 1.0) , ddd, (8.1, 7.1, 1.0) 7.08, d, (8.5) , br d, (8.1) 6.70, d, (8.0) , s 8

9 Table S4. 13 C NMR Data for Compounds in Methanol-d 4 (100 MHz) position a a a b OCH 2 O OCH NCH

10 Table S5. AChE Inhibitory Activities of Alkaloids 1 24 a compounds IC 50 (μm) R 2 compounds IC 50 (μm) R 2 1 > ± > ± ± > > > > > > b 1.25 ± > ± > ± > ± > > > > ± > a IC 50 values are expressed as the mean ± SD (n =3). b Galanthamine (18) was used as a positive control. Table S6. Inhibitory Effects of Alkaloids 1 24 a on the LPS-Induced NO Production in RAW264.7 Mouse Macrophages and the Cell Survival Rate compounds IC 50 (μm) R 2 survival rates (%) of RAW at 200 μm LPS (0 μg/ml) LPS (1 μg/ml) ± ± ± ± ± ± ± ± ± ± ± 2 99 ± ± ± ± 3 dexamethasone b 0.63 ± ± ± 2 a Data are expressed as the mean ± SD. Other alkaloids, IC 50 > 200 μm. b Dexamethasone was used a positive control. 10

11 Extraction and Isolation. The dried whole plants of Z. candida (50 kg) were extracted with 95% aqueous EtOH at room temperature (25 L 4, each for one week). Each filtrate was concentrated and combined to afford a crude residue (3.78 kg). The residue was suspended in H 2 O (6 L), adjusted to ph = 2 with 0.3 M HCl,and extracted with CHCl 3 (10 3 L). The aqueous phase was adjusted to ph = 10 using an ammonia solution, and extracted with CHCl 3 (4 3 L) to afford 40 g CHCl 3 extract. Finally, the aqueous phase was partitioned with n-buoh to get 215 g n-buoh extract. The CHCl 3 extract (40 g) was subjected to silica gel CC (CHCl 3 MeOH, from 1:0 to 1:1) to afford five fractions (Fr. 1 5). Fr.1 was fractionated on a silica gel CC eluted with petroleum ether acetone (from 15:1 to 2:1), and then separated by RP HPLC (MeOH H 2 O Et 2 NH, 69.8:30:0.2) to afford compounds 12 (3.9 mg, t R 44.2 min), 23 (2.3 mg, 24.4 min), and 14 (3.5 mg, 29.6 min). Fr.2 was subjected to silica gel CC (petroleum ether acetone, from 12:1 to 2:1) to give four subfractions (Fr. 2A Fr.2D). Using RP HPLC (MeOH H 2 O Et 2 NH, 72.8:27:0.2), 7 (11.4 mg, t R 15.9 min) and 11 (4.7 mg, t R 36.6 min) were purified from the subfraction Fr.2AA, while, 13 (3.0 mg, t R 47.0 min), 8 (5.6 mg, t R 52.7 min), and 9 (10.1 mg, t R 62.4 min) were isolated from the subfraction Fr.2AB. Compounds 16 (11 mg, t R 32.1 min), 22 (2.8 mg, t R 18.6 min), and 10 (5.7 mg, t R 21.2 min) were separated from subfractions Fr.2B, Fr.2C, and Fr.2D, respectively, by RP C 18 HPLC with a mobile phase of MeCN H 2 O Et 2 NH (47:53:0.2), MeOH H 2 O Et 2 NH (59.8:40:0.2), and MeOH H 2 O (60:40), respectively. Fr.3 was subjected to repeated Sephadex LH-20 CC (MeOH) and RP C 18 MPLC (MeOH H 2 O, from 30:70 to 50:50) to yield subfractions Fr.3A and Fr.3B. Fr.3A was separated by RP HPLC (MeCN H 2 O Et 2 NH, 21.8:78:0.2) to yield 20 (48.2 mg, t R 45 min) and 18 (57.8 mg, t R 50 min). Compounds 15 (2.8 mg, t R 28.1 min) and 24 (9.2 mg, t R 32.5 min) were isolated from Fr.3B by RP HPLC (MeCN H 2 O Et 2 NH, 29.8:70:0.2). Fr.4 was fractionated by a silica gel CC (CHCl 3 MeOH, 100:1, 50:1, 20:1) to give two subfractions Fr.4A and Fr.4B. Compound 17 (258 mg) was isolated from Fr.4A by re-crystallization. Purification of Fr.4B by RP C 18 HPLC (MeOH H 2 O Et 2 NH, 34.8:65:0.2) afforded compound 1 (5.8 mg, t R 39.5 min). Fr.5 was fractionated using a silica gel CC (CHCl 3 MeOH, 50:1, 10:1, 5:1), and then purified by HPLC over a Welch AQ C 18 column (MeCN H 2 O Et 2 NH, 7.8:92:0.2) to get 4 (3 mg, t R 22.3 min) and 5 (4 mg, t R 23.8 min). The n-buoh extract (215 g) was subjected to a silica gel CC (CHCl 3 MeOH, from 30:1 to 1:1) to afford four fractions (Fr. I IV). Fr. I was fractionated by an RP C 18 CC (MeOH H 2 O, 0:100, 20:80), then purified by Sephadex LH-20 (MeOH), silica gel CC (CHCl 3 MeOH, 20:1, 3:1), and finally by RP HPLC (MeOH H 2 O Et 2 NH, 29.8:70:0.2) to yield 19 (28.2 mg, t R 18.0 min) and 21 (38.7 mg, t R 20.0 min). Fr. II was separated by an RP C 18 CC (MeOH H 2 O, 0:100), and then purified by HPLC over a Welch AQ C 18 column (MeCN H 2 O Et 2 NH, 0.8:99:0.2) to get 3 (4.3 mg, t R 24.7 min). The MeOH-insoluble solid was filtered out from Fr. III, and identified to be lycorine by co-tlc analysis with the authentic sample. Then, the filtrate of Fr. III was concentrated and fractionated by silica gel CC (CHCl 3 MeOH, from 30:1 to 3:1), Sephadex LH-20 CC (MeOH), and RP HPLC (MeOH H 2 O Et 2 NH, 9.8:90:0.2) to achieve compound 2 (5.8 mg, t R 29.3 min). In a similar manner, compound 6 (2.3 mg, t R 53.5 min) was finally isolated from Fr. IV by RP 11

12 HPLC (MeOH H 2 O Et 2 NH, 25:74.8:0.2). 12

13 Figure S1. Comparison of ECD spectra for 1 6 and 17 in MeOH. Figure S2. Comparison of ECD spectra for 7 16 and 22 in MeOH. 13

14 Figure S3. Data fitting curves of the AChE inhibitory activities of compounds 3, 12 14, and Figure S4. Data fitting curves of the inhibitory effects of compounds 10 12, 14, 16, and dexamethasone on the LPS-induced NO production in RAW264.7 mouse macrophages 14

15 zgq #28 RT: 0.48 AV: 1 NL: 1.23E6 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S5. (+)-HR-ESI-MS spectrum of 1. Figure S6. UV spectrum of 1 in MeOH. 15

16 Figure S7. ECD spectrum of 1 in MeOH. Transmittance [%] Wavenumber cm Figure S8. IR spectrum of 1. 16

17 Figure S9. 1 H NMR (400 MHz) spectrum of 1 in CD 3 OD. Figure S C NMR (100 MHz) spectrum of 1 in CD 3 OD. 17

18 Figure S11. DEPT 135 spectrum of 1 in CD 3 OD. Figure S12. HSQC spectrum of 1 in CD 3 OD. 18

19 Figure S13. HMBC spectrum of 1 in CD 3 OD. Figure S14. 1 H- 1 H COSY spectrum of 1 in CD 3 OD. 19

20 Figure S15. NOESY spectrum of 1 in CD 3 OD. ZGQ #22 RT: 0.31 AV: 1 NL: 1.19E8 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S16. (+)-HR-ESI-MS spectrum of 2. 20

21 Figure S17. UV spectrum of 2 in MeOH. Figure S18. ECD spectrum of 2 in MeOH. 21

22 E:\ 同济医学院 \ 姚广民 \ \ZGQ Transmittance [%] Wavenumber cm Figure S19. IR spectrum of 2. Figure S20. 1 H NMR (400 MHz) spectrum of 2 in CD 3 OD. 22

23 Figure S C NMR (00 MHz) spectrumof 2 in CD 3 OD. Figure S22. DEPT 135 spectrum of 2 in CD 3 OD. 23

24 Figure S23. HSQC spectrum of 2 in CD 3 OD. Figure S24. HMBC spectrum of 2 in CD 3 OD. 24

25 Figure S25. 1 H- 1 H COSY spectrum of 2 in CD 3 OD. Figure S26. NOESY spectrum of 2 in CD 3 OD. 25

26 ZGQ #23 RT: 0.32 AV: 1 NL: 6.31E7 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S27. (+)-HR-ESI-MS spectrum of 3. Figure S28. UV spectrum of 3 in MeOH. 26

27 Figure S29. CD spectrum of 3 in MeOH. E:\ 同济医学院 \ 姚广民 \ IR\ZGQ Transmittance [%] Wavenumber cm-1 Figure S30. IR spectrum of 3. 27

28 Figure S31. 1 H NMR (400 MHz) spectrum of 3 in CD 3 OD. Figure S C NMR (100 MHz) spectrum of 3 in CD 3 OD. 28

29 Figure S33. DEPT 135 spectrum of 3 in CD 3 OD. Figure S34. HSQC spectrum of 3 in CD 3 OD. 29

30 Figure S35.HMBC spectrum of 3 in CD 3 OD. Figure S36. 1 H- 1 H COSY spectrum of 3 in CD 3 OD. 30

31 Figure S37. NOESY spectrum of 3 in CD 3 OD. zgq #22 RT: 0.32 AV: 1 NL: 2.30E7 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S38. (+)-HR-ESI-MS spectrum of 4. 31

32 Figure S39. UV spectrum of 4 in MeOH. Figure S40. ECD spectrum of 4 in MeOH. 32

33 E:\ 同济医学院 \ 姚广民 \ \ZGQ Transmittance [%] Wavenumber cm Figure S41. IR spectrum of 4. Figure S42. 1 H NMR (400 MHz) spectrum of 4 in CD 3 OD. 33

34 Figure S C NMR (100 MHz) spectrumof 4 in CD 3 OD. Figure S44. DEPT 135 spectrum of 4 in CD 3 OD. 34

35 Figure S45. HSQC spectrum of 4 in CD 3 OD. Figure S46. HMBC spectrum of 4 in CD 3 OD. 35

36 Figure S47. 1 H- 1 H COSY spectrum of 4 in CD 3 OD. Figure S48. NOESY spectrum of 4 in CD 3 OD. 36

37 zgq #20 RT: 0.31 AV: 1 NL: 2.80E7 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S49. (+)-HR-ESI-MS spectrum of 5. Figure S50. UV spectrum of 5 in MeOH. 37

38 Figure S51. ECD spectrum of 5 in MeOH. E:\ 同济医学院 \ 姚广民 \ \ZGQ Transmittance [%] Wavenumber cm Figure S52. IR spectrum of 5. 38

39 Figure S53. 1 H NMR (400 MHz) spectrum of 5 in CD 3 OD. Figure S C NMR (100 MHz) spectrum of 5 in CD 3 OD. 39

40 Figure S55. DEPT 135 spectrum of 5 in CD 3 OD. Figure S56. HSQC spectrum of 5 in CD 3 OD. 40

41 Figure S57.HMBC spectrum of 5 in CD 3 OD. Figure S58. 1 H- 1 H COSY spectrum of 5 in CD 3 OD. 41

42 Figure S59. NOESY spectrum of 5 in CD 3 OD. zgq #25 RT: 0.43 AV: 1 NL: 3.99E5 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S60. (+)-HR-ESI-MS spectrum of 6. 42

43 Figure S61. UV spectrum of 6 in MeOH. Figure S62. ECD spectrum of 6 in MeOH. 43

44 E:\ 同济医学院 \ 姚广民 \ IR\ZGQ Transmittance [%] Wavenumber cm-1 Figure S63. IR spectrum of 6. Figure S64. 1 H NMR (400 MHz) spectrum of 6 in CD 3 OD. 44

45 Figure S C NMR (100 MHz) spectrum of 6 in CD 3 OD. Figure S66. DEPT 135 spectrum of 6 in CD 3 OD. 45

46 Figure S67. HSQC spectrum of 6 in CD 3 OD. Figure S68. HMBC spectrum of 6 in CD 3 OD. 46

47 Figure S69. 1 H- 1 H COSY spectrum of 6 in CD 3 OD. Figure S70. NOESY spectrum of 6 in CD 3 OD. 47

48 zgq #27 RT: 0.46 AV: 1 NL: 9.76E5 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S71. (+)-HR-ESI-MS spectrum of 7. Figure S72. UV spectrum of 7 in MeOH. 48

49 Figure S73. ECD spectrum of 7 in MeOH. E:\ 同济医学院 \ 姚广民 \ \ZGQ Transmittance [%] Wavenumber cm Figure S74. IR spectrum of 7. 49

50 Figure S75. 1 H NMR (400 MHz) spectrum of 7 in CD 3 OD. Figure S C NMR (100 MHz) spectrum of 7 in CD 3 OD. 50

51 Figure S77. DEPT 135 spectrum of 7 in CD 3 OD. Figure S78. HSQC spectrum of 7 in CD 3 OD. 51

52 Figure S79. HMBC spectrum of 7 in CD 3 OD. Figure S80. 1 H- 1 H COSY spectrum of 7 in CD 3 OD. 52

53 zgq #24 RT: 0.41 AV: 1 NL: 4.51E5 T: FTMS + p ESI Full ms [ ] Figure S81. NOESY spectrum of 7 in CD 3 OD. 70 Relative Abundance m/z Figure S82. (+)-HR-ESI-MS spectrum of 8. 53

54 Figure S83. UV spectrum of 8 in MeOH. Figure S84. ECD spectrum of 8 in MeOH. 54

55 E:\ 同济医学院 \ 姚广民 \ IR\ZGQ Transmittance [%] Wavenumber cm Figure S85. IR spectrum of 8. Figure S86. 1 H NMR (400 MHz) spectrum of 8 in CD 3 OD. 55

56 Figure S C NMR (100 MHz) spectrum of 8 in CD 3 OD. Figure S88. DEPT 135 spectrum of 8 in CD 3 OD. 56

57 Figure S89. HSQC spectrum of 8 in CD 3 OD. Figure S90. HMBC spectrum of 8 in CD 3 OD. 57

58 Figure S91. 1 H- 1 H COSY spectrum of 8 in CD 3 OD. Figure S92. NOESY spectrum of 8 in CD 3 OD. 58

59 zgq #28 RT: 0.48 AV: 1 NL: 6.82E5 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S93. (+)-HR-ESI-MS spectrum of 9. Figure S94. UV spectrum of 9 in MeOH. 59

60 E:\ 同济医学院 \ 姚广民 \ \ZGQ Figure S95. ECD spectrum of 9 in MeOH. Transmittance [%] Wavenumber cm Figure S96. IR spectrum of 9. 60

61 Figure S97. 1 H NMR (400 MHz) spectrum of 9 in CD 3 OD. Figure S C NMR (100 MHz) spectrum of 9 in CD 3 OD. 61

62 Figure S99. DEPT 135 spectrum of 9 in CD 3 OD. Figure S100. HSQC spectrum of 9 in CD 3 OD. 62

63 Figure S101. HMBC spectrum of 9 in CD 3 OD. Figure S H- 1 H COSY spectrum of 9 in CD 3 OD. 63

64 Intens. Figure S103. NOESY spectrum of 9 in CD 3 OD MS, min # m/z Figure S104. (+)-HR-ESI-MS spectrum of

65 Figure S105. UV spectrum of 10 in MeOH. Figure S106. ECD spectrum of 10 in MeOH. 65

66 E:\ 同济医学院 \ 姚广民 \ \ZGQ Transmittance [%] Wavenumber cm-1 Figure S107. IR spectrum of 10. Figure S H NMR (400 MHz) spectrum of 10 in CD 3 OD. 66

67 Figure S C NMR (100 MHz) spectrum of 10 in CD 3 OD. Figure S110. DEPT 135 spectrum of 10 in CD 3 OD. 67

68 Figure S111. HSQC spectrum of 10 in CD 3 OD. Figure S112.HMBC spectrum of 10 in CD 3 OD. 68

69 Figure S H- 1 H COSY spectrum of 10 in CD 3 OD. Figure S114. NOESY spectrum of 10 in CD 3 OD. 69

70 zgq #28 RT: 0.48 AV: 1 NL: 2.02E6 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S115. (+)-HR-ESI-MS spectrum of Figure S116. UV spectrum of 11 in MeOH. 70

71 Figure S117. ECD spectrum of 11 in MeOH. E:\ 同济医学院 \ 姚广民 \ IR\ZGQ Transmittance [%] Wavenumber cm Figure S118. IR spectrum of

72 Figure S H NMR (400 MHz) spectrum of 11 in CD 3 OD. Figure S C NMR (100 MHz) spectrum of 11 in CD 3 OD. 72

73 Figure S121. DEPT 135 spectrum of 11 in CD 3 OD. Figure S122. HSQC spectrum of 11 in CD 3 OD. 73

74 Figure S123. HMBC spectrum of 11 in CD 3 OD. Figure S H- 1 H COSY spectrum of 11 in CD 3 OD. 74

75 Figure S125. NOESY spectrum of 11 in CD 3 OD. ZGQ #26 RT: 0.36 AV: 1 NL: 1.32E8 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S126. (+)-HR-ESI-MS spectrum of

76 Figure S127. UV spectrum of 12 in MeOH. Figure S128. ECD spectrum of 12 in MeOH. 76

77 E:\ 同济医学院 \ 姚广民 \ \ZGQ Transmittance [%] Wavenumber cm Figure S129. IR spectrum of 12. Figure S H NMR (400 MHz) spectrum of 12 in CD 3 OD. 77

78 Figure S C NMR (100 MHz) spectrum of 12 in CD 3 OD. Figure S132. DEPT 135 spectrum of 12 in CD 3 OD. 78

79 Figure S133. HSQC spectrum of 12 in CD 3 OD. Figure S134. HMBC spectrum of 12 in CD 3 OD. 79

80 Figure S H- 1 H COSY spectrum of 12 in CD 3 OD. Figure S136. NOESY spectrum of 12 in CD 3 OD. 80

81 zgq #17 RT: 0.28 AV: 1 NL: 3.89E3 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S137. (+)-HR-ESI-MS spectrum of 13. Figure S138. UV spectrum of 13 in MeOH. 81

82 Figure S139. ECD spectrum of 13 in MeOH. E:\ 同济医学院 \ 姚广民 \ \ZGQ Transmittance [%] Wavenumber cm Figure S140. IR spectrum of

83 Figure S H NMR (400 MHz) spectrum of 13 in CD 3 OD. Figure S C NMR (100 MHz) spectrum of 13 in CD 3 OD. 83

84 Figure S143. DEPT 135 spectrum of 13 in CD 3 OD. Figure S144. HSQC spectrum of 13 in CD 3 OD. 84

85 Figure S145. HMBC spectrum of 13 in CD 3 OD. Figure S H- 1 H COSY spectrum of 13 in CD 3 OD. 85

86 ZGQ #27 RT: 0.38 AV: 1 NL: 2.73E5 T: FTMS + p ESI Full ms [ ] Figure S147. NOESY spectrum of 13 in CD 3 OD Relative Abundance m/z Figure S148. (+)-HR-ESI-MS spectrum of

87 Figure S149. UV spectrum of 14 in MeOH Figure S150. ECD spectrum of 14 in MeOH. 87

88 E:\ 同济医学院 \ 姚广民 \ \ZGQ Transmittance [%] Wavenumber cm-1 Figure S151. IR spectrum of 14. Figure S H NMR (400 MHz) spectrum of 14 in CD 3 OD. 88

89 Figure S C NMR (100 MHz) spectrum of 14 in CD 3 OD. Figure S154. DEPT 135 spectrum of 14 in CD 3 OD. 89

90 Figure S155. HSQC spectrum of 14 in CD 3 OD. Figure S156.HMBC spectrum of 14 in CD 3 OD. 90

91 Figure S H- 1 H COSY spectrum of 14 in CD 3 OD. Figure S158. NOESY spectrum of 14 in CD 3 OD. 91

92 ZGQ #25 RT: 0.35 AV: 1 NL: 3.08E7 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S159. (+)-HR-ESI-MS spectrum of 15. Figure S160. UV spectrum of 15 in MeOH. 92

93 E:\ 同济医学院 \ 姚广民 \ \ZGQ Figure S161. ECD spectrum of 15 in MeOH Transmittance [%] Wavenumber cm Figure S162. IR spectrum of

94 Figure S H NMR (400 MHz) spectrum of 15 in CD 3 OD. Figure S C NMR (100 MHz) spectrum of 15 in CD 3 OD. 94

95 Figure S165. DEPT 135 spectrum of 15 in CD 3 OD. Figure S166. HSQC spectrum of 15 in CD 3 OD. 95

96 Figure S167. HMBC spectrum of 15 in CD 3 OD. Figure S H- 1 H COSY spectrum of 15 in CD 3 OD. 96

97 Figure S169. NOESY spectrum of 15 in CD 3 OD. ZGQ #25 RT: 0.35 AV: 1 NL: 4.41E7 T: FTMS + p ESI Full ms [ ] Relative Abundance m/z Figure S170. (+)-HR-ESI-MS spectrum of

98 Figure S171. UV spectrum of 16 in MeOH. Figure S172. ECD spectrum of 16 in MeOH. 98

99 E:\ 同济医学院 \ 姚广民 \ IR\ZGQ Transmittance [%] Wavenumber cm-1 Figure S173. IR spectrum of 16. Figure S H NMR (400 MHz) spectrum of 16 in CD 3 OD. 99

100 Figure S C NMR (100 MHz) spectrum of 16 in CD 3 OD. Figure S176. DEPT 135 spectrum of 16 in CD 3 OD. 100

101 Figure S177. HSQC spectrum of 16 in CD 3 OD. Figure S178.HMBC spectrum of 16 in CD 3 OD. 101

102 Figure S H- 1 H COSY spectrum of 16 in CD 3 OD. Figure S180. NOESY spectrum of 16 in CD 3 OD. 102