1-(乙基-Leu-AA-OBzl)-β-咔啉-3-羧酸苄酯、制备、结构和应用_2

文档序号:9539516阅读:来源:国知局
化合物,为淡黄色油状 物。ESr-MS(m/e) ;663[M+H]+;[a^j0 =-3.3(C=0. 3,邸30巧;1H-NMR(300MHz,CDCls) : 5/ ppm= 10. 37 (s,IH),8. 74 (s,IH),8. 14 (d,J= 7.8Hz,IH),7. 74 (s,IH),7. 29-7. 56 (m,13H), 5. 52 (s, 2H), 5. 29 (m, 2H), 4. 81 (m,IH), 3. 55 (m,IH), 3. 42 (m,IH), 3. 22 (m, 2H),I. 94 (s,IH), 1.50-1.77(111,細),0.93(111,12).。(:-醒尺(751化,〔0(:13):5/卵111= 174.35,165.97,143.59, 140. 81,136. 33,134. 97,128. 71,128. 56,128. 41,128. 36,128. 20,127.99,121.98,121.78, 120. 64,116. 77,112. 12,67. 39,66. 97,61. 94,50. 82,47. 23,42. 87,41. 16,29. 69,25. 14, 25. 00,23. 10,22. 93,21. 80,21. 54。
[0034] 实施例7制备I- (N-己基-Leu-Ala-OBzI)-目-巧晰-3-駿酸予醋(4b)
[0035] 按照实施例6的方法,从600mg(1.74mol)l-(2-氧代己基)-目-巧晰-3-駿酸 予醋和767mg(2.eimmol)肥1 ?Leu-Ala-OBzl得到208mg(19% )标题化合物,为淡黄色油 状物。ESr-MS(m/e) ;621[M+H]+;树O=-2.3(C= 0.3,邸3地);1H-NMR(300MHz,CDCls): 5/ppm= 11.41 (s,lH),8.39 (s,lH),8.35 (s,lH),8.02 (d,J= 1.8Hz,1H),7. 55-7. :M(m, TH), 7. 28-7. 20 (m,6H), 5. 44 (s, 2H), 5. 09 (m, 2H), 4. 67 (m,IH), 3. 63 (m, 2H), 3. 48 (m, 2H), 3. 32(m,lH),2. 07(s,lH),1.80(m,3H),1.42(d,J= 13. 8Hz,3H),0. 99(d,J= 5. 7Hz,2H), 0. 99 (d,J= 5. 7Hz,2H)."C-NMR(75MHz,CDCI3): 5 /卵m= 172. 90,171. 33,165. 59,162. 62, 142. 92,140. 98,136. 10,135. 63,135. 12,128. 63,128. 56,128. 44,128. 39,128. 35,127. 98, 127.88, 121. 50, 121. 40, 120. 59,116. 43,112. 46,67. 12,67. 02,61. 53,48. 06,46. 02, 41. 46, 36. 47, 31. 46, 24. 98, 22. 54, 22. 33,17. 51。
[0036] 实施例8制备I-(N-己基-Leu-Ile-OBzl)-目-巧晰-3-駿酸予醋(4c)
[0037] 按照实施例6的方法,从600mg(l. 74mol) 1-(2-氧代己基)-目-巧晰-3-駿酸予醋 和897mg(2. eimmol)肥I . Leu-Ile-OBzl得到160mg(14% )标题化合物,为淡黄色油状物。ESr-MS(m/e) ;663[M+H]+ ;[a]〇=-3.0(C = 0. 3,邸3地);1H-NMR(300MHz,DMSO) : 5 /ppm = 10. 36(s,lH),8. 78(s,lH),8. 16(d,J= 6Hz,lH),7. 95(d,J= 9,1H),7. 56-7. 28(m,12H), 5. 53 (s, 2H), 5. 24 (m, 2H), 5. 16 (m,IH), 4. 78 (s,IH), 3. 23 (m, 2H), 3. 20 (m, 3H) ,1.71 (m, 2H), I. 43(m,3H),1.28(m,lH),0. 76(m,12H)."C-NMR(75MHz,CDCI3) : 5/ppm= 173. 52,165. 99, 143. 61,140. 82,136. 98,136. 40,134. 95,128. 71,128. 60,128. 54,128.38,128.28,128.15, 128. 12, 127. 98, 122. 07, 121. 82,120. 62,116. 75,112. 06,67. 36,66. 93,61. 98,56. 08, 47. 40,43. 12, 36. 05, 25. 15, 25. 01,24. 93, 23. 40,16. 01,11. 20〇
[0038] 实施例9制备I- (N-己基-Leu-Met-OBzI)-目-巧晰-3-駿酸予醋(4d)
[0039] 按照实施例6的方法,从600mg(l. 74mol) 1-(2-氧代己基)-目-巧晰-3-駿酸予醋 和918mg(2.eimmol)肥1 .Leu-Met-OBzl得到156mg(13% )标题化合物,为淡黄色油状物。 ESr-MS(m/e) ;681[M+H]+;[a]〇= -2.3(c=0.3,CH3〇H) ;iH-NMR(300MHz,CDCl3) :5/ppm= 10. 60 (s,IH),8. 67 (s,IH),8. 12 (d,J= 6Hz,2H),7. 28-7. 56 (m,12H),5. 51 (s,IH),5. 28 (d, J= 12Hz,2H),5. 16(d,J= 12Hz,2H),4. 90(s,lH),3. 55(s,lH),3. 37(m,2H),3. 22(m,2H), 2. 69 (m,IH), 2. 51 (m, 2H), 2. 18 (m,IH), 2. 12 (m, 3H),I. 73 (m,IH),I. 67 (m, 2H), 0. 96 (d,J= 6Hz,2H),0. 90(d,J= 6Hz,2H)."C-NMR(75MHz,CDCl3) : 5/ppm= 172. 81,165. 91,143. 47, 140. 82,136. 15,1:34. 86,128. 71,128. 63,128. 53,128. 41,128. 30,128. 24,128. 11,121. 90, 121. 73,120. 67,116. 69,112. 17,67. 54,67. 10,61. 79,54. 00,53. 38,51. 04,46. 96,43. 24, 42. 66,32. 90,31. 49,30. 17,29. 91,25. 09,24. 31,23. 21,22. 91,21. 17,15. 50,15. 17。
[0040] 实施例10制备I- (N-己基-Leu-Tyr-OBzI)-目-巧晰-3-駿酸予醋(4e)
[00川按照实施例6的方法,从600mg(l. 74mol) 1-(2-氧代己基)-目-巧晰-3-駿酸予醋 和1.Olg化eimmol)肥1 .Leu-Tyr-OBzl得到146mg(ll% )标题化合物,为淡黄色油状物。 ESr-MS(m/e) ;713[M+H]+;怕〇 = -9.3(C= 0. 3,邸3〇巧;iH-NMR(300MHz,CDCl3) : 5 /卵m= II. 00(S,1H),8. 0 (d,J=6. 9Hz,1H),7. 19-7. 52 (m,15H),6. 91 (d,J= 7. 82Hz,2H),6. 73 (d, J= 7. 8Hz,2H),5. 42(m,2H),5. 19(m,2H),4. 98(m,lH),3. 73(m,lH),3. 14(m,2H),2. 87(m, 1H),2. 77(m,2H),l. 58(m,3H),l. 25(m,2H),0. 90,(d,J= 4. 2Hz,2H),0. 81(d,J= 5.IHz, 2H). "c-醒R(75MHz,CDCI3): 5 /卵m= 171. 62,165. 96,155. 90,140. 88,136. 38,134. 94, 130. 40,128. 99,128. 70,128. 65,128. 61,128. 58,128. 51,128. 47,128. 33,120. 66,116. 76, 116. 34,116. 15,115. 53,112. 23,67. 46,67. 28,61. 65,53. 47,52. 75,46. 30,44. 09,42. 44, 37. 09, 29.68, 24. 89, 23. 30, 22. 13, 21. 35, 21. 30。
[004引实施例11制备I-(N-己基-Leu-T巧-OBz1)-目-巧晰-3-駿酸予醋(4f)
[0043]按照实施例6的方法,从600mg(l. 74mol) 1-(2-氧代己基)-目-巧晰-3-駿酸予 醋和1. 06g(2.eimmol)肥1 .Leu-T巧-OBzl得到170mg(13% )标题化合物,为淡黄色粉末。 ESr-MS(m/e) :736[M+田+;Mpl23-124 2C; [a]^j〇=-3.3(C= 0. 3,邸3〇巧;1H-NMR(300MHz, CDCI3);S/ppm= 9.8(s,lH),8. 21(s,lH),7. 93(d,J=6. 9Hz,lH),7. 13-7. 55(m,17H), 6. 67 (s,IH),5. 44 (m,2H),5. 18 (m,2H),5. 06 (m,IH),3. 72 (m,IH),3. 34 (m,2H),3. 08 (m,IH), I. 65 (m,4H),I. 25 (m,IH),I. 06 (s,3H),0. 85 (m,4H),0. 70 (m,2H). "c-醒R(75MHz,CDCI3): 5/ppm= 171. 16,165. 10,142. 74,140. 88,136. 22,136. 01,135.14,128.70,128.59, 128. 53,128. 43,128. 34,127. 19,124. 01,122. 49,121. 62,118.91,116.43,111.57, 111. 23, 109. 16,67. 38,67. 07,52. 62,40. 56,27. 72,24. 79,22. 08,21. 67,20. 67。
[0044] 实施例12制备I- (N-己基-Leu-Va^OBzl)-目-巧晰-3-駿酸予醋(4g)
[0045] 按照实施例6的方法,从600mg(l. 74mol) 1-(2-氧代己基)-目-巧晰-3-駿酸予 醋和835mg(2. eimmol)肥1 . Leu-Val-OBzl得到286mg(25% )标题化合物,为淡黄色油状 物。ESr-MS(m/e) ;649[M+H]+ ;的2〇〇=-2.0 (C = 0. 3,邸3〇巧;1H-NMR(300MHz,CDCI3) : 5 / ppm= 11. 25 (s, 1H),8. 35 (s, 3H),7. 99 (d,J= 3. 3Hz,IH),7. 19-7. 56 (m, 12H),5. 48 (m, 2H),5. 15 (m, 2H),4. 62 (m,IH),3. 90 (s,IH),3.6(m, 2H),3. 43 (s, 2H),2. 32 (m,IH),2. 07 (s,IH), 1.95(m,lH),1.77(m,2H),0. 96(m,12H)."C-NMR(75MHz,CDCI3) : 5/ppm= 173. 02,165. 96, 143. 60,140. 99,136. 33,136. 17,135. 01,128. 68,128. 55,128. 38,128. :34,128. 18,128. 13, 121. 97,121. 75,120. 48,116. 73,112. 18,67. 28,66. 95,61. 87,56. 62,47. 12,42. 90,32.66, 25. 08, 23. 05, 22.68, 21. 79,19. 23,17. 47。
[0046] 实施例13制备I-(N-己基-Leu-Gl厂OBzl)-目-巧晰-3-駿酸予醋(4h)
[0047] 按照实施例6的方法,从600mg(l. 74mol) 1-(2-氧代己基)-目-巧晰-3-駿酸予 醋和678mg化eimmol)肥1 ?Leu-Gl厂OBzl得到123mg(12% )标题化合物,为淡黄色油状 物。ESr-MS(m/e) ;607[M+H]+;[a]2〇〇= -〇.7(c = 0.3,CH3〇H) ;iH-NMR(300MHz,CDCl3) :5/卵m =11.41 (s,lH),8.91 (s,lH),8.34 (s,lH),8.01 (d,J= 11.7Hz,2H) ,7.22-7. 54 (m,12H), 5. 42 (m, 2H),5. 10 (s, 2H),4. 12 (m, 2H),3.
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