一类倍半萜类抗溃疡药物,制备方法及用图_2

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5。
[002引(2R, 3R, 3aR,6R, 7aS)-3-hyd;roxy-3, 6-dimethyl-2-(化)-3-methy Ibut-1-en-1-y1)hexahydro benzofuran-4 (2H)-one(B02) : white solids; Yield 15 84-86 °C;MS(ESI)m/z:275.18 (M+Nar;IR:Vmax/cmi(K Br) 3435, 2961,2929, 1694, 1455, 1379, 1229, 1142, 1085 ;1h應R(CDC!3, 400MHz) δ : 5.86(dd, J = 14.8,8. 4Hz, IH),5. 44 (dd, J = 15.6,6.細z, IH),4. 45-4. 37 (m, IH, CH),4. 01 (d, J =6.8Hz, IH, CH),2. 73 (d, J = 9. 2Hz, IH),2. 41-2. 36 (m, 2H, 2 X CH),2. 23-2. 16 (m, 1 H, CH), 2. 10-1. 99 (m, IH, CH), L 79-1. 72 (m, IH, CH), 1. 62-1. 49 (m, 2H, CH, OH), L 31 (s, 3H, C &),1.02(d, J =6.4Hz,9H,3XCH3) ;"C NMR(CDCl3, lOOMHz) δ :210. 2, 144. 7, 120. 6,87. 1, 80. 3, 77. 1, 59. 3, 49. 9, 39. 7, 31. 1, 26. 5, 23. 1, 22. 2, 22. 1, 21. 70
[0030] (3R, 3aR, 7aS, Z)-3-hydroxy-3,6-dime thy 1-2-(3-me thy Ibuty 1 i de ne)-3, 3a, 7, 7a-tetrahydro benzofuran-4(2H)-one(B15) :white solids;Yield 30 99-101 °C;MS(ESI)m/z:273.14 (M+Nar;IR:Vmax/cmi(K 化)3380, 2954, 2867, 1689, 1652, 1435, 1383, 1260, 1125, 1062,931 ;1h NMR(CDC!3, 400MHz) δ : 5. 97 (d, J = 1. 2Hz, IH, = CH),4. 80 (dd, J = 13. 2,6. 4Hz, IH, CH),4. 51 (t, J = 7. 4Hz ,IH, CH),3. 21〇3rs,IH, OH),2. 74-2.66(m, 2H, CH2),2. 65 (d, J =6.8Hz, IH, CH),2. 00 (s, 3 H, CH3),1. 92 (t, J = 7. 2Hz, 2H,邸2),1. 59 (s, 3H, CH3),0. 87 (d, J =6. 4Hz,6H, 2 X CH3) ;"C NMR(CDCl3, lOOMHz) δ:197. 0, 160. 3, 159. 2, 127. 1, 95. 5, 77. 9, 75. 4, 54. 0, 35. 0, 33. 5, 28. 6, 27. 2, 24.6, 22. 3, 22. 0〇
[0031] (3R, 3aR, 6R, 7aS)-3-hydroxy-2-isopentyl-3, 6-dimethylh exahydrobenzofuran-4(2H)-one(B53):whitesolids;Yield5 % ; m. p. 1 2 2- 1 2 4 °C;MS(ESI)m/z:277. 17(M + Na)";IR: v ' (K Br):M03, 2962, 2869, 1696, 1460, 1381,1260, 1229, 1152, 1085, 1007, 805 :? NMR(CDCl3, 400 MHz) δ :4. 39-4. 31 (m, IH, CH), 3. 44(dd, J =8. 0, 4. OHz, IH, CH), 2. 70(d, J = 9. 2Hz, IH,畑),2. 42 (d, J = 16. 4Hz, IH,畑),2. 25-2. 18 (m, IH, CH),1. 99 (dd, J = 16.8, 12.8Hz, IH, CH),1. 82-1. 74 (m, IH, CH),1. 63-1. 41 (m, 3H, 3 X CH),1. 38 (s, 3H, (?),1. 03(d, J =6. 4Hz,3H,C册),0. 91(d, J =6. 4Hz,細,2XCH3) ;"C NMR(CDCl3, 100 MHz) δ :211 .0,86. 5, 80. 3, 76. 3, 59.6, 49.8, 39. 9, 35. 9, 28. 2, 26. 5, 26. 2, 23. 2, 22. 5, 22. 4, 21.6。
[003引 (2Z, 3R, 3aR, 4E, 6S, 7aS)-3-hyd;roxy-3, 6-dimethyl-2-(3-methylb utylidene)hexahydrobenzofuran-4(2H)-oneoxime(B14) :whitesolids;Yield95 %;m.p.129-131°C ;MS(ESI)m/z:291. 18 (M+Na)";IR:v^^Jcm' (K Br) 3451,2955, 2868, 1639, 1462, 1385, 1165, 1098, 1038, 985 ;1h匪R(CDC!3,400MHz)δ: 8. 49 (s,IH) , 4. 54 - 4. 42 (m, 2H) , 3. 24 - 3. 10 (m,IH) , 2. 74 (d,J= 8.0Hz,lH),1.96(t,J= 7.1Hz,3H),1.85(s,lH),1.73(dd,J=15.4,12.6Hz,2H),1.65-1.54(m,3H),1.45(s,3H),1.03(d,J= 6.3Hz,3H),0.89(d,J= 6. 6Hz,7H) ;1化 NMR(CDCl3, 100MHz)δ :160. 36, 158. 55, 95. 73, 78. 66, 78. 18, 50. 33, 37. 74, 33. 75, 31. 76, 2 8. 73, 26. 94, 26. 08, 22. 36, 22. 24, 21. 780
[0033] (3R, 3aR, 6S, 7aS,E)-3-hydroxy-2-isopentyl-3, 6-dimethyl hexahydrobenzofuran-4(2H)-oneoxime(B68) :whitesolids;Yield92 %;m.p. 137-139°C ; MS(ESI) m/z: 2 9 2. 1 7(M+Na)+; I R: v max/cm1化 Br) 3456, 2955, 2868, 1639, 1462, 1385, 1165, 1098, 1038, 985 ;1h匪R(CDCl3, 400MHz)δ:8. 11 (s,IH), 4. 28 - 4. 19(m,IH), 3. 55(dd,J= 7. 8, 4.IHz,IH), 3. 15 (d,J= 14.6Hz,lH),2.75(d,J= 9.2Hz,lH),2.05(dd,J=11.8,6.6Hz,lH),1.66(s,2H),1.63-1.56(m,lH),1.56 - 1.44(m,5H),1.40(d,J=11.5Hz,lH),1.35(s,lH),1.30(s,3H),1.27- 1. 18(m,2H), 1.01(d, J = 6. 2Hz,3H),0. 90(d, J = 6. 4Hz,7H) ;1化NMR(CDCl3, 100 MHz) δ :1 59. 32, 86. 72, 80. 31, 76. 47, 51. 21, 40. 32, 35. 96, 32. 32, 28. 28, 27. 01, 26. 88, 23. 23, 22. 56 ,22. 44, 21. 92。
[0034] Ethyl2-(((E)-((3R, 3aR,6S, 7aS, Z)-3-hydroxy-3,6-dime thyl-2-(3-methylbutylidene)hexahydrobenzofuran-4(2H)-ylide ne)amino)oxy)acetate(B33) : colorless oil ;Yield 71 %;I R : v cm i(KBr)3456,2955,2868, 1639, 1462, 1385, 1165, 1098, 1038,985 ;1h NMR(CDCl3, 400 MHz) δ:4. 64 - 4. 56 (m, 3H) , 4. 48 (t, J = 7. 5Hz, 2H) , 4. 27 - 4. 13 (m, 3H), 3. 13 (ddd, J = 7.6, 5. 2, 2. 3Hz, IH), 2. 72 (d, J =8. 4Hz, IH), 2. 24 - 2. 00(m,3H),1.96(dd,J = 15. 5,8.4Hz,4H),1.76(dd,J = 16. 1,11. Wz,2H),1.66- 1. 49 (m, 5H),1. 42 (s, 4H),1. 27 (t, J = 7. IHz, 6H),1. 01 (d, J = 6. 2Hz, 5H),0. 88 (dd, J = 6. 6, 1. 3Hz, 9H) ;"C NMR(CDCl3, 100 MHz) δ : 170. 34, 160. 06, 159. 61,95. 92, 78. 47, 78. 29, 70. 25, 60. 87, 49. 97, 37. 61, 33. 82, 32. 91, 28. 72, 26. 77, 26. 35, 22. 32, 22. 21, 21. 71, 14. 15〇 [003引(2Z, 3R, 3aR, 4E, 6S, 7aS)-3-hyd;roxy-3, 6-dimethyl-2-(3-methylbutyl i dene)hexahydrobenzofuran-4(2H)-one 0-(3-fluorobenzoyl)oxime(B62): white solids ;Yield 67 % ;m. p.131-1:34°C ;MS (ESI) m/z : 402. 17 (M+Na)+; IR: v max/cm1 (KBr) 3456, 2955, 2868, 1639, 1462, 1385, 1165, 1098, 1038, 985 ;1h應R(CDC!3, 400 MHz) δ :7. 92 - 7. 83 (m, IH), 7. 75(ddd, J = 9. 2, 2. 5, 1. 5Hz, IH), 7. 46(td, J = 8. 0, 5. 5Hz, IH),7. 30 (tdd, J =8. 3, 2.6, 0.細z, IH),4. 55 (化,J = 10. 4,6. 9Hz, 2H),3. 23 - 3. 12 (m, IH), 3. 06 (d, J =8. IHz, IH) , 2. 06 (dd, J = 11. 4,6. OHz, IH) , 2. 02 - 1. 93 (m, 3H),1. 75 (d, J = 16. 3Hz, 2H),1. 64 (ddd, J = 20. 0, 15. 9, 9. OHz, 3H),1. 56 (s, 3H),1 .25 (s, IH),1. 08 (d, J =6. 2Hz, 3H),0. 90 (d, J =6.6Hz,6H) ;"C NMR(CDCl3, lOOMHz) δ : 168 .11, 160. 20, 130. 27, 130. 19, 125. 41, 125. 38, 120. 31, 116.
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