新型羟基双氢青蒿素衍生物及其应用_3

文档序号:9318658阅读:来源:国知局
5, 138. 88,137. 95,132. 00,131. 93,131. 84,129. 26,129. 23,129. 17,129. 14,124. 50,124. 47, 122.42,122.31,120.48,120.41,120.10,120.04,116.37,116.15,104.61,91.90,91.22, 79. 13,75. 61,49. 07,42. 76,41. 34,36. 09,31. 68,27. 54,25. 92,24. 57, 15. 44, 12. 05. HRESIMSm/z619. 2107 [M+Na]+(calcdforC33H34F2Na08,619. 2114).
[0095] 实施例12 :9a,12a-二_(间甲氧基肉桂酸)双氢青蒿素酯的制备
[0096] 按照实施例1的方法,用原料间甲氧基肉桂酸代替实施例1中的原料肉桂酸而制 备标题化合物。
[0097] 白色粉末,产率 42%。4NMR(400MHz,Chloroform-d)S= 7. 77(d,J= 16. 0, 1H),7. 69 (d,J= 16. 0,1H),7. 33 (td,J= 7. 9,4. 9, 2H),7. 15 (t,J= 6. 7, 2H),7. 07 (dt, J= 5.3,2.0,2H),6.97(ddd,J= 8.2,3.5,2.2,2H),6.50(d,J= 16.0,lH),6.44(d,J =16.0,1H),5.96 (d,J= 9.8,1H),5.61 (s,lH),4.66 (td,J= 10. 8,4.4,1H),3.86 (s, 3H),3. 85 (s,3H),2. 77-2. 65 (m,1H),2. 51-2. 38 (m,1H),2. 22-2. 08 (m,2H),2. 00-1. 92 (m, 2H),1. 73-1. 55(m,4H),1. 48(s,3H),1. 03(d,J= 6. 2,3H),0? 93(d,J= 7. 1,3H).13C 匪R(101MHz,Chloroform-d)S= 166.45,165.36,159.96,159.93,146.17,145.25, 135. 64,135. 62,129. 93,120. 94,120. 83,118. 16,117. 75,116. 57,116. 39,113. 00,112. 95, 104. 60,91. 81,91. 21,79. 13,75. 47, 55. 32, 55. 30,49. 07,42. 76,41. 39,36. 09,31. 71, 27. 57,25. 91,24. 58,15. 44,12. 04.HRESIMSm/z643. 2502 [M+Na]+(calcdforC35H40Na010, 643. 2514).
[0098] 实施例13 :9a,12a_二_(间氯肉桂酸)双氢青蒿素酯的制备
[0099] 按照实施例1的方法,用原料间氯肉桂酸代替实施例1中的原料肉桂酸而制备标 题化合物。
[0100] 白色粉末,产率 49%/HNMR(400MHz,Chloroform-d)s=7.73(d,J= 16.0,1H), 7. 65 (d,J= 16. 0,1H),7. 54 (dd,J= 9. 7,1. 8, 2H),7. 48-7. 32 (m,6H),6. 50 (d,J= 16. 0, 1H),6. 45 (d,J= 16. 0,1H),5. 95 (d,J= 9. 8,1H),5. 61 (s,1H),4. 65 (td,J= 10. 8,4. 4, 1H),2. 79-2. 63 (m,1H),2. 51-2. 39 (m,1H),2. 23-2. 07 (m,2H),1. 95 (dt,J= 13. 8,4. 4, 2H), 1. 62(dtd,J= 27. 4,11. 0,5. 4,4H),1. 48(s,3H),1. 03(d,J= 6. 2,3H),0? 92(d,J= 7. 1, 3H). 13CNMR(101MHz,Chloroform-d)S= 166. 08,165. 01,144. 58,143. 69,136. 09,136. 06, 134. 99,130. 40,130. 33,130. 18,128. 01,127. 89,126. 30,119. 34,118.94,104.62,91.94, 91. 20,79. 08,75. 69,49. 04,42. 74,41. 34, 36. 07,31. 65,27. 52,25. 90,24. 56, 15. 43, 12. 03.HRESIMSm/z651. 1515 [M+Na]+(calcdforC33H34Cl2Na08,651. 15 2 3).
[0101] 实施例14 :9a,12a-二_(2,6_二氯肉桂酸)双氢青蒿素酯的制备
[0102] 按照实施例1的方法,用原料2,6-二氯肉桂酸代替实施例1中的原料肉桂酸而制 备标题化合物。
[0103] 白色绒毛状结晶,产率 61%。4NMR(400MHz,Chloroform-d)S= 7. 89(d,J= 16. 4,1H),7. 82(d,J= 16. 4,1H),7. 37(dd,J= 8. 0,6. 5,4H),7. 20(td,J= 8. 1,4. 8,2H), 6. 67 (d,J= 16. 4,1H),6. 62 (d,J= 16. 4,1H),5. 95 (d,J= 9. 8,1H),5. 61 (s,1H),4. 64 (td, J= 10.8,4.5,lH),2.75-2.64(m,lH),2.50-2.38(m,lH),2.21(dt,J= 12.9,4.3,1H), 2.15-2. 06(m,1H),1. 94(dt,J= 9. 2,4. 6,2H),1. 75-1. 50(m,4H),1. 47(s,3H),1. 03(d,J =6. 3,3H),0? 93(d,J= 7. 1,3H).13CNMR(101MHz,Chloroform-d)S= 165. 80,164. 78, 139. 67,138. 73,135. 13,135. 08,131. 77,129. 99,128. 85,126. 44,126. 03,104. 64,92. 07, 91. 26,79. 10,75. 94,49. 06,42. 76,41. 29,36. 07,31. 67,27. 49,25. 93,24. 55, 15. 46, 12. 08.HRESIMSm/z719. 0755 [M+Na]+(calcdforC33H32Cl4Na08, 7 1 9 . 0 7 43).
[0104]实施例15 :9a,12a-二-(3,4_二甲氧基肉桂酸)双氢青蒿素酯的制备
[0105] 按照实施例1的方法,用原料3,4_二甲氧基肉桂酸代替实施例1中的原料肉桂酸 而制备标题化合物。
[0106] 白色粉末,产率 53%。4NMR(400MHz,Chloroform-d)S= 7. 72(d,J= 15. 9, 1H),7. 64 (d,J= 15. 9,1H),7. 17-7. 09 (m,2H),7. 06 (dd,J= 4. 9,1. 9, 2H),6. 87 (dd,J= 8. 4,4. 4, 2H),6. 36 (d,J= 15. 9,1H),6. 30 (d,J= 15. 9,1H),5. 94 (d,J= 9. 8,1H),5. 59 (s, lH),4.63(td,J= 10. 9,4.5,1H),3.93 (s,3H),3.92 (s,3H),3.91 (s,6H),2.67 (ddd,J =9.8,7.1,4.7,lH),2.48-2.37(m,lH),2.19-2.05(m,2H),1.92(dt,J= 9.0,4.4,2H), 1. 59(dtt,J= 22. 7,15. 9,8. 0,4H),1. 46(s,3H),1. 01(d,J= 6. 2,3H),0? 90(d,J= 7. 1, 3H).13CNMR(101MHz,Chloroform-d)S= 166. 74,165. 64,151. 37,151. 30,149. 28,149. 26, 146. 16,145. 23,127. 27,122. 85,122. 71,115. 52,115. 11,111. 07,109. 74,104. 59,91. 67, 91. 21,79. 15,77. 22,75. 23,55. 99,55. 91,55. 88,49. 06,42. 77,41. 45,36. 09,31. 74, 27. 63,25. 92,24. 59,15. 45,12. 06.HRESIMSm/z703. 2736 [M+Na]+(cacldforC37H44Na012, 703. 2725).
[0107]实施例16 :9a,12a-二-(2, 3,4-三甲氧基肉桂酸)双氢青蒿素酯的制备
[0108] 按照实施例1的方法,用原料2, 3,4-三甲氧基肉桂酸代替实施例1中的原料肉桂 酸而制备标题化合物。
[0109] 白色粉末,产率 58%。4NMR(400MHz,Chloroform-d)S= 7. 94(d,J= 16. 2, 1H),7. 88(d,J= 16. 2,1H),7. 27(t,J= 8. 7,2H),6. 70(dd,J= 8. 8,4. 1,2H),6. 49(d, J= 16. 1,1H),6. 42(d,J= 16. 1,1H),5. 93(d,J= 9. 8,1H),5. 60(s,1H),4. 62(td,J= 10. 9,4. 3,1H),3. 95 (s,3H),3. 92 (s,3H),3. 90 (s,3H),3. 89 (s,3H),3. 88 (s,3H),3. 87 (s, 3H),2.68(ddd,J= 9.8,7.2,4.6,lH),2.53-2.34(m,lH),2.16(dt,J= 12.7,4.2,1H), 2. 12-2.04(m,lH),1.98-1.89(m,2H),1.56(td,J= 11.2,6.0,4H),1.46(s,3H),1.01(d, J= 6.2,3H),0.90 (d,J= 7.1,3H).13C匪R(101MHz,Chloroform-d)S= 167.08, 166. 00,155. 75,155. 68,153. 51,153. 40,142. 38,141. 34,140. 29,123. 62,123. 39,121. 36, 116. 73,116. 38,107. 60,104. 56,91. 65,91. 23,79. 23,75. 20,61. 47,61. 44,60. 90,56. 08, 49. 12,42. 80,41. 40,36. 11,31. 74, 27. 61,25. 96,24. 58, 15. 44, 12. 07.HRESIMSm/z 763. 2956 [M+Na]+(calcdforC39H48Na014, 763. 2936).
[0110] 实施例17 :9a,12a-二-(3,4, 5-三甲氧基肉桂酸)双氢青蒿素酯的制备
[0111] 按照实施例1的方法,用原料3,4,5_三甲氧基肉桂酸代替实施例1中的原料肉桂 酸而制备标题化合物。
[0112] 白色粉末,产率 56%。4NMR(400MHz,Chloroform-d)S= 7. 70(d,J= 15. 9, 1H),7. 62 (d,J= 15. 9,1H),6. 77 (d,J= 3. 8,4H),6. 40 (d,J= 15. 9,1H),6. 34 (d,J= 15. 9,1H),5. 94 (d,J= 9. 8,1H),5. 59 (s,1H),4. 64 (td,J= 10. 8,4. 3,1H),3. 90 (s,6H), 3.89 (s,9H),3. 88 (s,3H),2. 68 (ddd,J= 9. 8, 7. 2,4. 7,1H),2. 50-2. 35 (m,1H),2. 13 (ddd, J= 23. 0,11. 7,7. 6,2H),1. 92(dt,J= 9. 1,4. 4,2H),1. 76-1. 49(m,4H),1. 45(d,J= 5.1,3H),1.01(d,J= 6.1,3H),0.91(d,J= 7.1,3H).13CNMR(101MHz,Chloroform-d) S= 166. 45,165. 39,153. 48,153. 46,146. 24,145. 31,140. 32,129. 73,129. 70,117. 05, 116. 63,105. 39,105. 33,105. 27,104. 63,91. 75,91. 21,79. 11,75. 37,60. 99,56. 18,56. 16, 49. 01,42. 74,41. 44,36. 07,31. 72,27. 61,25. 92,24. 59, 15. 46, 12. 06.HRESIMSm/z 763. 2951 [M+Na] +(calcdforC39H48Na014, 763. 2936).
[0113] 实施例18 :9a,12a-二_(氢化肉桂酸)双氢青蒿素酯的制备
[0114] 按照实施例1的方法,用原料氢化肉桂酸代替实施例1中的原料肉桂酸而制备标 题化合物。
[0115] 无色油状物,产率 53 %。虫NMR(400MHz,Chloroform-d)S= 7. 32-7. 26(m, 4H),7. 23-7. 18 (m,6H),5. 75 (d,J= 9. 8,1H),5. 46 (s,1H),4. 42 (td,J= 10. 7,4. 4,1H), 3. 05-2. 89 (m,4H),2. 81-2. 70 (m,2H),2. 66 (dd,J= 8. 4, 7. 0, 2H),2. 58-2. 47 (m,1H), 2. 44-2. 33 (m,1H),2. 09-2. 01 (m,1H),1. 95-1. 84 (m,2H),1. 79 (dt,J= 14. 4, 4. 4,1H), 1. 61-1. 45 (m,3H),1. 44 (s,3H),1. 35-1. 24 (m,1H),0? 86 (d,J= 5. 8, 3H),0? 71 (d,J= 7. 1, 3H).13CNMR(101MHz,Chloroform-d) 8 = 172.51,172.48,171.58,171.56,140.22,140. 14, 128. 54,128. 33,126. 44,126. 33,104.58,104.56,91.57,91. 10,79. 00,75. 40,48.92, 42. 58,42. 56,41. 06,36. 02,35. 96,35. 83,31. 44, 31. 05,30. 68,27. 22,25. 90,2
当前第3页1 2 3 4 5 6 
网友询问留言 已有0条留言
  • 还没有人留言评论。精彩留言会获得点赞!
1