4. 43, 123. 62, 115. 52, 81. 90, 74. 40, 65. 80, 63. 13, 45. 30, 44. 94, 40. 90, 39. 12, 29. 92, 27. 87, 25. 91,23. 39, 23. 12, 20. 72, 18. 68, 17. 93 ;MS ESI (m/z) :444 [M+H]+。 阳0間实施例3 :
[0083] 化合物3的制备
[0084]
[0085] 将20mg化合物11溶于2血四氨巧喃,(TC下加入2eq.化I,0°C揽拌15min,加 入2eq.二乙胺升溫至室溫揽拌12h,减压蒸除溶剂,得到黄色油状物。该油状物经硅胶 柱层析(石油酸:乙酸乙醋=3:1~1:1)得到淡黄色油状物。Ihnmr化OOMHz,CDCI3) 56. 42(d,J = 16. 4Hz,lH),6. 04(d,J = 16. 4Hz,lH),5. 83(dd,J = 12. 8,3. 6Hz,lH),5 .79 (s, 2H),5. 64 (d, J = 16. 2Hz, IH),5. 61 (s, IH),5. :M (d, J = 9. IHz, IH),5. 19 (dd, J =16. 2, 9. IHz, IH), 5. 12(t, J =6. 9Hz, IH), 3. 46 (d, J = 14. 3Hz, IH), 2. 92 (d, J = 14. 7Hz, IH),2. 62 (dq, J = 14. 3, 7. 2Hz, 3H),2. 44 (td, J = 13.8,6. 9Hz, 4H),2. 20 (s, overla ped, 7H),2. 03 (d, J = 14. 5Hz, 2H),I. 94 (s, overlaped,8H),I. 69 (s, 3H),I. 59 (s, 3H),I. 39 (s,細),I. 05 - 0. 98 (m, overlaped, 18H). "C NMR (150MHz, CDCI3) 5 203. 09, 167. 33, 159. 42 ,153.88, 145. 92, 142. 34, 131. 93, 129. 06, 124. 46, 123. 39, 115. 56, 81. 92, 74. 34,68. 14, 63 .38, 57. 76, 53. 03, 46. 97, 46. 82, 44. 89, 40. 65, 39. 09, 29. 87, 27. 81, 25. 82, 23. 32, 23. 04, 2 0. 65, 18. 70, 17. 84, 11. 96,8. 24 ;MS ESI (m/z) : 472 [M+田+。
[0086] 实施例4 :
[0087] 化合物4的制备
[0088]
[0089]将20mg化合物11溶于2血四氨巧喃,0 °C下加入2eq.化1,0 °C揽 拌15min,加入2eq.二异丙基胺升溫至室溫揽拌12h,减压蒸除溶剂,得到黄 色油状物。该油状物经硅胶柱层析(石油酸:乙酸乙醋= 3:1~1:1)得到淡 黄色油状物。古醒尺(6001化,〔0(:13)5 6.41((1,1=16.3化,1巧,6.05扣1 = 13. 6Hz,lH),5.86(t,J = 15. lHz,lH),5.80(dd,J = 10. 0,8.細z,2H),5. 61(d,J = 16. OHz, IH),5. 37 - 5. 29 (m, IH),5. 21 - 5. 15 (m, IH),5. 15 - 5. IO (m, IH),3. 43 (t, J = 29.5Hz,3H),3.14-2.98(m,ove;rlaped,6H),2.23-2.16(m,ove;rlaped,7H),2.05-1. 96 (m, overlaped, 4H), I. 94(s,6H), I. 92 - I.86(m, 3H), I. 85(s, IH), I. 84 -I. 75(m,3H),1.69(d,J = 9. lHz,overlaped,5H),1.63(d,J = 4. 2Hz,lH),1.60(d,J = 7. 4Hz, overlaped, 5H),I. 40 - I. 37 (m, overlaped, 5H),I. 05 - 0. 94 (m, overlaped, IOH)."C NMR(150MHz, CDCI3) 5 203.88, 167. 55, 159.68, 153. 83, 146. 21, 131. 97, 129. 20, 124. 53, 12 3. 10, 115. 52, 82. 23, 74.日1,49. 12, 47. 89, 47. 65, 44. 67, 40. 67, 39. 10, 27. 87, 25. 91,23. 34 ,23. 09, 21. 95, 20. 69, 19. 77, 18. 77, 17. 87 ;MS ESI (m/z) : 500 [M+H]+。
[0090] 实施例5
[0091] 化合物5的制备:
[0092]
阳09引将20mg化合物11溶于2血四氨巧喃,(TC下加入2eq.化I,0°C揽拌15min,加入 2eq.吗啡嘟升溫至室溫揽拌化,减压蒸除溶剂,得到黄色油状物。该油状物经硅胶柱层析 (石油酸:乙酸乙醋=4 :1~1 :1)得到淡黄色油状物。电NMR巧OOMHz, CDCU 5 6. 39化J =16. 4Hz, 1H),6.02化J=16. 4Hz, 1H),5. 78(S,2H),5. 62化J=16. IHz, 1H),5. 32化J =9. lHz,lH),5. 17(dd,J = 16. 2,9. lHz,lH),5. 10(t,J = 6. 9Hz,lH),3. 31(d,J = 13. 9Hz, IH),2. 83 (d, J = 13. 9Hz, IH),2. 48 (s, 2H),2. :M (s, 4H),2. 19 (s, 5H),2. Ol (s, 2H), I. 96 (d, J = 5. 4Hz, 2H),I. 93 (s,細),1.87 - 1.80(111,3巧,1.68(3,3巧,1.55(3,4巧,1.45-1.39(m,4H),1.37(s,4H),1.01(s,3H). ;MS ESI(m/z):484[M+H]+。
[0094] 实施例6 : 阳0巧]化合物6的制备
[0096]
[0097] 将20mg化合物11溶于2血四氨巧喃,(TC下加入2eq.化I,0°C揽拌15min,加入 2eq.赃晚升溫至室溫揽拌化,减压蒸除溶剂,得到黄色油状物。该油状物经硅胶柱层析(石 油酸:乙酸乙醋=4 :1~2 :1)得到淡黄色油状物。ESI:咱NMR巧OOMHz,CDCU5 6. 39化J =16. 4Hz, 1H),6.02 化J=16. 4Hz, 1H),5. 78(S,2H),5. 62 化J=16.IHz, 1H),5. 32 化J =9.lHz,lH),5. 17(dd,J= 16. 2,9.lHz,lH),5. 10(t,J= 6. 9Hz,lH),3. 31(d,J= 13. 9Hz,IH),2. 83 (d,J= 13. 9Hz,IH),2. 48 (s, 2H),2.:M(s, 3H),2. 19 (s, 3H),2.Ol(s, 3H), 1.96(d,J= 5.4Hz,2H),1.93(s,6H),1.87 - 1.80(m,3H),1.68(s,3H),1.55(s,3H),1.45-1.39(m,4H),1.37(s,3H),1.01(s,3H).;MSESI(m/z):484[M+H]\
[0098]实施例7 :
[0099] 化合物7的制备 阳 100]
阳1〇U 将20mg化合物11溶于2血四氨巧喃,(TC下加入2eq.化I,0°C揽拌15min,加入 2eq.化咯烧升溫至室溫揽拌2地,减压蒸除溶剂,得到黄色油状物。该油状物经硅胶柱层析(石油酸:乙酸乙醋=5 :1~1 :2)得到淡黄色油状物。电NMR化OOMHz, CDCU 56. 47化J =16. 4Hz, 1H),6.05化J = 16. 4Hz, 1H),5. 89 (dd, J = 12. 0, 4. IHz, 2H),5. 79(S,1H),5.66 (d, J = 16. 2Hz, 1H),5. 36 (d, J = 9. IHz, 1H),5. 19 (dd, J = 16. 2, 9. IHz, 2H),5. 11 (t, J = 7. OHz, IH),3. 46 (d, J = 13. 9Hz, IH),3. 10 (d, J = 13. 9Hz, IH),2. 56 (t, J = 9.細z, TH),2. 2 0 (s,6H),2. 05 (s, 3H),I. 94 (d, J = 0.細z,6H),I. 69 (s, 3H),I. 59 (s, 3H),I. 45 (dd, J = 10. 3 ,4.8Hz, 2H),I. 38 (s, 3H),I. 02 (s, 3H)."C NMR(150MHz,CDCI3) 5 202.66, 167. 46, 159. 63, I 53. 92, 145. 93, 131. 95, 131. 35, 131. 14, 129. 06, 129. 02, 128. 90, 124. 46, 123. 39, 115. 51,8 2. 03, 74. 43, 71. 99, 65. 78, 60. 63, 60. 04, 44. 98, 40. 74, 39. 13, 30. 73, 27. 85, 25. 91,25. 89, 23. 36, 23. 09, 20. 69, 19. 37, 19. 36, 18. 72, 17.88, 17. 85, 14. 39 ;MS ESI (m/z) : 470 [M+H]+。 阳102] 实施例8 : 阳103] 化合物8的制备 阳 104]
阳1〇5] 将20mg化合物11溶于2血四氨巧喃,0 °C下加入2eq.化I,0 °C揽拌15min, 加入2eq.N-甲基赃嗦升溫至室溫揽拌2地,减压蒸除溶剂,得到黄色油状物。该 油状物经硅胶柱层析(石油酸:乙酸乙醋= 2:1~1:4)得到淡黄色油状物。Ih NMR(500MHz,CDCl3) 5 6. 42 (d,J= 16. 4Hz,lH),6. 04(d,J= 16. 5Hz,lH),5. 81(d,J= 12. 7Hz, IH),5. 78 (s, IH),5. 59 (d, J = 16. IHz, IH),5. 30 (d, J = 9. IHz, IH),5. 18 (dd, J =16. I, 9. IHz, IH) , 5. 09 (s, IH) , 3. 48 (d, J = I 3. 3Hz , IH) , 3. 0 I (d, J = 13.7Hz, IH),2. 70 (d, J = 35. 7Hz, 12H),2. 48 (s, 3H),2. 43 (s, 3H),2. 19 (s, 3H),2. 03 (d, J = 12. 2Hz, 2H),I. 94 (s, 3H),I. 87 (dd, J = 23. 1,13. OHz, 4H),I. 68 (s, 3H),I. 44 (s, IH),I. 37 ( s, 3H),I. 25 (m, IH),I. 09 (m, IH),I. 02 (s, 3H) ;MS ESI (m/z):499 [M+田 \ 阳106] 实施例9 : 阳107] 化合物9的制备 阳10引
[0109] 将IOOmgvibsaninB溶于5血二氯甲烧,-78°C下揽拌0.化,然后缓慢滴加3eq. DAST,