一类黄烷化合物,其制备方法及降糖活性的制作方法_2

文档序号:9365615阅读:来源:国知局
,5. 83 (1H,d,J = 2. 0, 6-H),5. 44 (1H,s,3-H),5. 23 (1H,s,2-H),4. 05 (2H,s,S-C-H ),4. 04(1H, d, J = 2.0, 4-H) ;13C NMR(125MHz, DMS〇-d6) 8:165. I (〇-C-〇),158. I (C-5),157. 2(C-7), 155. 4(C-9), 145. 4(C-3/7 ,5/7 ),144. 9(0-3',4'), 138. 9(C-4/7 ), 138. 0(〇-1/7 ' ),13 I. 3(C-4",),130. 7(C-2",,6",),128.5(01^ ),128. 2(C-3",,5",),118. 5(C-1 "),117.5(06,),115.2(05,),114.2(02,),108. 6(C-2" ,6" ),96. 9(C-10), 95. 9(C-6), 94. 0 (C-8),72. 7 (C-2),71. 2 (C-3),40. 0 (C-4),35. 0 (S-C)?
[0122] 实施例34-⑶-(4-甲氧基苄硫基)_表儿茶素没食子酸酯(JP-3)的制备
[0123] 制备方法同制备例2,所用黄烷聚合物原料为大花红景天50%部位,所用硫代试 剂为4-甲氧基苄硫醇,高效制备液相60% (Me0H/H20体积比)得到化合物JP-3,白色粉末, 收率31. 3%。
[0124] 化合物的核磁数据如下:
[0125] [a]';; -89,1° (cO. IMeOH) ;HR-ESI-MS (m/z595. 1265[M+H]+, calcd, 595. 1269); 1H NMR (500MHz, DMS0-d6) 8 :7. 37 (2H,m, 2/7 ' , 6/7 ' -H), 6. 90 (2H, m, 3/7 ', 5,r '-H ),6.84(lH,s,2,-H) ,6.79(2? s, 2" ,6" -H) ,6.67(2? m, 5,,6,-H) ,5.92(1? d, J =2. 5, 8-H),5. 83 (1H,d,J = 2. 5, 6-H),5. 44 (1H,s,3-H),5. 25 (1H,s,2-H),4. 08 ( lH,d,J = 2.0, 4-H) ,4.00 (2H,dd,J = 27. 0,13.5, S-C-H) ,3.75 (3H,s,-OCH3) ;13C NMR (125MHz,DMS0-d6)S:165. 0 (O-C-O),158.I(C-5),157. 9 (C-4" ' ),157.I(C_7),155. 3 (C-9), 145. 4(C-3/7 ,5/7 ),144. 8(0-3',4'), 138. 8(C-4/7 ), 130. 4(C-1/7 ' ), 129. 9(C-2/7 ', 6"' ),128.5(C-1,),118.6(C-l"),117.4(C-6, ),115.1(05' ),114.1(C-2,),113.7( C-3",,5",),108. 6(C-2",6" ),97.1(010),95.9(06),94.0(08),72.6(02),71. 2(C-3 ),55.0 (C-OCH3),45. 6 (C-4),35. 2 (S-C).
[0126] 实施例44-⑶-(2, 4, 6-三甲基苄硫基)_表儿茶素没食子酸酯(JP-4)的制备
[0127] 制备方法同制备例2,所用黄烷聚合物原料为大花红景天50%部位,所用硫代试 剂为2, 4, 6-三甲基苄硫醇,高效制备液相70% (Me0H/H20体积比)得到化合物JP-4,白色 粉末,收率29. 8%。
[0128] 化合物的核磁数据如下:
[0129] [a];;;~2(rJ (cO. IMeOH) ;HR-ESI-MS (m/z607. 1643 [M+H]+, calcd, 607. 1646); 1H NMR (500MHz, DMS〇-d6)8 :6. 88 (1H, d, J=I. 5, 2'-H), 6. 86 (2H, s, 2", 6"-H), 6. 82 (2H, s, 3", ,5 " ,-H),6. 79 (1H, dd, J = 8. 5, I. 5, 6, _H),6. 72 (1H, d, J = I. 5, 5,-H),5. 96 (1H,d,J = 2. 5, 8-H),5. 84 (1H,d,J = 2. 5, 6-H),5. 45 (1H,s,3-H),5. 33 ( 1H,s,2-H),4.14(2H,s,4-H),4.05(1H,s,S-C-H),2.42(6H,s,2",,6",-CH3),2.22(3H,s, 4",-CH3) ;13C NMR(125MHz,DMS0-d6)S:165. 2 (O-C-O),158. O (C-5),157. 4 (C-7),155. 2 (C-9),145. 5(C-3",5" ),145. 0(03,,4,),138. 9(C-4" ),136. 5(C-2",,6",),135. 9(C-1" ,),130. 3(C-4" ' ),128. 7(C-3" ',5" '),128.6(01'),118. 6(C-1" ),117. 5(06') ,115.3(05,),114.I(C-2,),108. 7 (C-2",6" ),97.3 (C-IO),96.0(06),94.1(08),73.1(C -2),71.7(C-3),40.6(C-4),31.1(S-C),20.6(C-4〃,013),19.1(02"',6"'CH3).
[0130] 实施例54-(S)-(2-氯苄硫基)_表儿茶素没食子酸酯(JP-5)的制备
[0131] 制备方法同制备例2,所用黄烷聚合物原料为大花红景天50%部位,所用硫代试 剂为2-氯苄硫醇,高效制备液相65% (Me0H/H20体积比)得到化合物JP-5,白色粉末,收 率 31. 5%〇
[0132] 化合物的核磁数据如下:
[0133][a] -99.;^ (cO. IMeOH);HR-ESI-MS (m/z599. 0791 [M+H]+, calcd, 599. 0773) NMR(500MHz,DMS0-d6)S:7.59(lH,m,3",-H),7.48(lH,m,5",-H),7.31(2H,m,4",,6 ",-H),6.83(1? s, 2,-H),6.80(2? s, 2",6" -H),6.68(2? m, 5,,6,-H),5.91(1? d,J =2. 0, 8-H),5. 82 (1H,d,J = 2. 0, 6-H),5. 44 (1H,s,3-H),5. 30 (1H,s,2-H),4. 15 (2H,m,S-C H2),4. 13 (1H,s,4-H) ;13C NMR(125MHz,DMS0-d6) S : 165. 2 (O-C-O),158. I (C-5),157. 2 (C-7) ,155.5(C-9),145.5(C-3",5" ),144.9(C-3,),138.9(C-4,),136.0(C-4" ),133.2(C-6", ,1,),131. I (C-2" ' ),129. 5(C-1" ' ),128. 9(C-5" ' ),128. 5(C-3" ' ),127. 2(C-4" ,),118. 5(C-1" ),117. 5(06,),115. 2(05,),114. 2(02,),108. 6(C-2",6" ),96. 8(C-1 0),95. 9 (C-6),94.O(C-8),72. 8 (C-2),71. 2 (C-3),33. 7 (C-4),30. 7 (S-C) ?
[0134] 实施例64-⑶-(4-氟苄硫基)_表儿茶素没食子酸酯(JP-6)的制备
[0135] 制备方法同制备例2,所用黄烷聚合物原料为大花红景天50%部位,所用硫代试 剂为4-氟苄硫醇,高效制备液相65% (Me0H/H20体积比)得到化合物JP-6,白色粉末,收 率 27. 9%。
[0136] 化合物的核磁数据如下:
[0137] [a] f;-iOi.i0 (cO. IMeOH);HR-ESI-MS (m/z583. 1065 [M+H]+, calcd, 583. 1069); 1H NMR (500MHz, DMS0-d6)S :7. 49 (2H, m, 2",,6",H),7. 48 (2H, m, 3",,5",H),7 ? 14(lH,s,2,-H),6.83(2H,s,2",6" -H),6.67(2H,brs,5,,6,-H),5.90(lH,d,J = 2. 0, 8-H),5. 81 (1H,d,J = 2. 0, 6-H),5. 42 (1H,s,3-H),5. 21 (1H,s,2-H),4. 05 (2H,m,S-C-H ),4.01(lH,d,J = 2.0,4-H) ;13CNMR(125MHz,DMS0-d6) S :165.1(0-C-0),160.2(C-4",), 158.0(C-5),157.2(C-7),155.4(C-9),145.4(C-3",5" ),144.9(C-3,,4'),138.9(C-4" ),13 5. 0(C-1" ' ),130. 8(C-2" ',6" '),128.5(01,),118. 4(C-1" ),117.5(06' ),115.2 (C-3",,5",),115. I (C-5,),114. 0(02,),108. 6(C-2",6" ),97.0(010),95.9(06),9 4. O (C-8),72. 7 (C-2),71. 2 (C-3),40.0 (C-4),34. 9 (S-C) ?
[0138] 实施例74-(S)-(2-吡嗪基乙硫基)_表儿茶素没食子酸酯(JP-7)的制备
[0139] 制备方法同制备例2,所用黄烷聚合物原料为大花红景天50%部位,所用硫代试 剂为2-吡嗪基乙硫醇,高效制备液相50% (Me0H/H20体积比)得到化合物JP-7,白色粉末, 收率19. 8%。
[0140] 化合物的核磁数据如下:
[0141] [a];,5 -93,6° (cO. IMeOH);HR-ESI-MS (m/z 581. 1232[M+H]+, calcd, 581. 1224) NMR (500MHz, DMS0-d6) 8 :8. 67 (lH,s, 6 /7 ' -H), 8. 59 (1H, s, 3 /7 ' -H), 8. 51 (1H, d, J = 2.0,5",-H) ,6.85 (lH,d, J =1.5,2,-H) ,6.80(2? s,2" ,6" -H) ,6.74 (lH,dd, J = 8. 0, I. 5, 6' -H), 6. 71(1H, d, J = 8. 0, 5' -H), 5. 95(1H, d, J = 2. 0, 8-H), 5. 83(1H, d, J = 2. 0, 6-H),5. 36 (1H, s, 3-H),5. 21 (1H, s, 2-H),4. 10 (1H, d, J =I.5, 4-H),3. 25 (2H, m, 2 ", -CH2),3. 18 (2H,m,S-CH2) ;13C NMR(125MHz,DMS0-d6) S : 165. 3 (O-C-O),158. 0 (C-5),157. 2 (C -7),155.5(09),155. 2(C-2",),145. 4(C-3",5" ),144. 9(03,,4',3",,6",),144.1( C-5/7 ' ), 142. 6(C-4/7 ),128. 3(0-1' ), 118. 4 (C-l/7 ),117. 5(0-6' ),115. 2(0-5' ),114. I (C-2' ), 108. 6 (C-2", 6/7 ), 97. 3 (C-IO), 95. 9 (C-6), 94. 0 (C-8), 72. 7 (C-2) ,71.8 (C-3), 40. 0 (C-4),34.I{2" '-CH2),30.1 (S-C).
[0142] 实施例84-⑶-(2-糠硫醇基)_表儿茶素没食子酸酯(JP-8)的制备
[0143] 制备方法同制备例2,所用黄烷聚合物原料为大花红景天50 %部位,所用硫代试 剂的2-糠硫醇,高效制备液相60% (Me0H/H20体积比)得到化合物JP-8,白色粉末,收率 33. 2%。
[0144] 化合物核磁数据如下:
[0145] [uj ;' -{31.5'?(cO. IMeOH) ;HR-ESI-MS (m/z555. 0966 [M+H]+,calcd, 555. 0956); 1H 匪R (500MHz, DMS0-d6) S :7. 62 (1H, dd, J = 8. 0, 1. 5, 5 " ,-H),6. 85 (1H,d,J = 1.5,2,-H),6.79(2H,s,2 ",6 " -H),6.73(2H,m,5,,6,-H),6.41(lH,d,J = 8. 0, 4" '-H), 6. 38 (1H, d, J = 8. 0, I. 5, 3" '-H),5. 92 (1H, d, J = I. 2, 8-H),5. 84 (1H, d, J = 1.2, 6-H),5. 42 (1H, s, 3-H),5. 27 (1H, s, 2-H),4. 13 (1H, d, J = 1. 2, 4-H),4. 08 (2H,s,S-C-H) ;13C NMR(125MHz,DMS0-d6) S : 165. O (O-C-O),158. O (C-5),157 ? 1(07),155.4(09),151. 5(C-2" ' ),145. 4(C-3",5" ),144. 8(03' ,4' ),142. 3(C-5", ),138.8(C-4"),128.5(C-1'),118.5(C-1" ),117.5(06' ),115.2(05' ),114.1(C-2, ),110. 5(C-4",),108. 6(C-2" ,6" ),107. 5(C-3",),96. 8(C-10), 95. 9(C-6), 94.0(08), 72. 6 (C-2),71. 0 (C-3),40. 0 (C-4),27. 9 (S-C).
[0146] 实施例94-⑶-(4-甲氧基苯硫基)_表儿茶素没食子酸酯(JP-9)的制备
[0147] 制备方法同制备例2,所用黄烷聚合物原料为大花红景天50 %部位,所用硫代试 剂为4-甲氧基苯硫酚,高效制备液相60% (Me0H/H20体积比)得到化合物JP-9,白色粉末, 收率25. 7%。
[0148] 化合物的核磁数据如下:
[0149] [0.];; -38.7° (cO.IMeOH) ;HR-ESI-MS(m/z581. 1117[M+H]+,calcd, 581. 1112); 1HNMR(500MHz,DMS〇-d6) 8 : 7. 56 (2H,d,J= 9. 0, 3" ,,5 " ,_H),7.OO(2H,d,J= 9.0,2" , ,6" , -H) ,6.82 (lH,d,J= 2.0,2, -H) ,6.72 (lH,dd,J= 8. 5,2.0,6,-H),6.69(2H,s,2 " ,6 " -H) ,6.67 (lH,d,J= 8.5,5 , -H) ,5.98 (lH,d,J= 2. 0, 8-H),5. 86 (1H,d,J = 2. 0, 6-H),5. 57 (1H,s,3-H),5. 13 (1H,brs,2-H),4. 32 (2H,d,J = 2. 0, 4-H),3. 79 (3H,s,-OCH3) ;13C NMR(125MHz,DMS0-d6) S : 164. 6 (O-C-O),159. 2 (C-5),158 .3(C-7), 157. 3(C-9), 155. 5(C-4/7 ' ),145.4(0-3^ ,5/7 ),144. 9(0-3',4f ), 138. 8(C-4/7 ),1 34. 4(C-2/7 ',6'rr ),128. 5(0-1' ),124.4(0-1^ ' ), 118. 4(C-l/7 ),117.4(0-6' ),115. 2(05,),114. 8(C-3",,5",),114.0(02,),108. 6(C-2" ,6" ),96. 6(C-10), 96.0(06), 94. I (C-8),72. 6 (C-2),70. 6 (C-3),55. 2 (C-OCH3),43. 3 (C-4) ?
[0150] 实施例104-(S)-(2-氨基苯硫基)_表儿茶素没食子酸酯(JP-IO)的制备
[0151] 制备方法同制备例2,所用黄烷聚合物原料为大花红景天50%部位,所用硫代试 剂为2-氨基苯硫酚,高效制备液相55% (Me0H/H20体积比)得到化合物JP-10,白色粉末, 收率27. 8%。
[0152] 化合物的核磁数据如下:
[0153] [aj^ -192.1° (CO. IMeOH) ;HR-ESI-MS(m/z588. 0931 [M+Na]+,calcd, 588. 0935); 1H NMR(500MHz,DMS0-d6) S :7. 38(1H,dd,J = 7. 5, I. 5, 6 ",_H),7. 14 (1H,m,4 ",_H), 6.88(lH,d,J = 2.0,2,-H) ,6.77 (2H,m,6,,5",-H) ,6.67 (lH,d,J = 8.5,5,-H),6 ? 66(2H,s,2",6" -H),6.57(1? m,3",-H),6.03(1? d,J = 2.5, 8-H),5.89(1? d,J = 2. 5, 6-H),5. 71 (1H,d,J = 2. 5, 3-H),5. 15 (1H,d,J = 2. 5, 2-H),4. 19 (1H,d,J = 2. 5, 4-H); 13C NMR(125MHz,DMS0-d6) S : 164. 3 (O-C-O),158. 3 (C-5),157. 3 (C-7),155. 8 (C-9),150. 6 (C -2",),145. 3(C-3",5" ),144.9(03,),144.8(04,),138. 7(C-4" ),136. 7(C-6",),13 0.6(01' ),128. 7 (C-4" ' ),118. 5(C-1" ),117.4(06' ),116. I (C-l" ' ),115.2(05' ),114.4(C-5",),114.0(02,),113. 2(C-3",),108. 5(C-2",6" ),96.7(010),96.0(06) ,94. 4 (C-8),72. 6 (C-2),70. 4 (C-3),40. 7 (C-4) ?
[0154] 实施例114-(S)-(4-氨基苯硫基)_表儿茶素没食子酸酯(JP-Il)的制备
[0155] 制备方法同制备例2,所用黄烷聚合物原料为大花红景天50%部位,所用硫代试 剂为4-氨基苯硫酚,高效制备液相55% (Me0H/H20体积比)得到化合物JP-Il,白色粉末, 收率27. 9%。
[0156] 化合物的核磁数据如下:
[0157] [a];/ (c0.IMeOH) ;HR-ESI-MS(m/z566.1132[M+H]+,calcd, 566. 1115) NMR (500MHz, DMS〇-d6) 8 : 7. 28 (2H, d, J = 8. 0, 2/7 ',6 ",_H),6. 82 (1H, s, 2,_H),6. 71 (I H,d,J = 8.5,6' -H),6.68(2H,s,2",6" -H),6.65(2H,d,J = 8.5,5' -H),6.60(2H,d,J = 8.0,3",,5",-H),5.91(1? d,J = 2.0, 8-H),5.83(1? d,J = 2.0, 6-H),5.57(1? s ,3-H),5. 15 (1H,s,2-H),4. 17 (1H,s,4-H) ;13C NMR(125MHz,DMS0-d6) S : 164. 5 (O-C-O),158. 0(C-5),157. 3(C-7),155.5(09),149. 3(C-4" ' ),145. 3(C-3",5" ),144. 9(C-3,),144. 8(C -4' ),138. 7(C-4" ),135. 5(C-2" ',6" ' ),128. 7(01,),118. 6(C-1" ' ),117. 4(C-1 "),117.2(06,),115.2(05,),114. 4(C-3",,5",),114.0(02,),108. 5(C-2",6"), 97. I (C-IO),95. 9 (C-6),94. I (C-8),72. 5 (C-2),70. 6 (C-3),40. 4 (C-4) ?
[0158] 实施例124-(S)-(4-羟基苯硫基)_表儿茶素没食子酸酯(JP-12)的制备
[0159] 制备方法同制备例2,所用黄烷聚合物原料为大花红景天50%部位,所用硫代试 剂为4-羟基苯硫酚,高效制备液相50% (Me0H/H20体积比)得到化合物JP-12,白色粉末, 收率13. 4%。
[0160] 化合物的核磁数据如下:
[0161] [a]? -29,16 (cO. IMeOH) ;HR-ESI-MS (m/z567. 0949[M+H]+, calcd, 567. 0956); 1H NMR (500MHz, DMS〇-d6) 8:7. 45 (2H, d, J = 8. 5, 2",,6 " ,-H),6. 82 (1H,d,J = 1.5,2,-H),6.80(2? d,J = 8. 5,3",,5",-H),6.73(1? dd,J = 8. 0,1.5, 6,-H),6. 7 0 (2H,s,2 ",6 " -H),6. 67 (1H,d,J = 8. 0, 5,-H),5. 98 (1H,d,J = 2. 0, 8-H),5. 85 (1H,d,J =2. 0, 6-H), 5. 49 (1H, s, 3-H),5. 12(1H, brs, 2-H), 4. 27 (1H, d, J = 2. 0, 4-H) ;13C NMR (125MHz, DMS0-d6)S :164. 6 (O-C-O),158. 2 (C-5),157. 7 (C-7),157. 3 (C-9),155. 5 (C-4 ",),145.4(C-3",5"),144.9(C-3,,4,),138.7(C-4"),135.2(C-2",,6",),128.6(C-1,),122. I (C-l" ' ),118. 5(C-1" ),117. 4(06' ),116. 2(C-3" ',5" '),115.2(05, ),114. O (C-2' ),108. 6 (C-2 ",6 " ),96. 8 (C-IO),96. O (C-6),94. I (C-8),72. 6 (C-2),70. 5 (C-3 ),43. 5 (C-4).
[0162] 实施例134-(S)-(3-甲氧基苯硫基)_表儿茶素没食子酸酯(JP-13)的制备
[0163] 制备方法同制备例2,所用黄烷聚合物原料为大花红景天50%部位,所用硫代试 剂为3-甲氧基苯硫酚,高效制备液相55% (Me0H/H20体积比)得到化合物JP-13,白色粉 末,收率23. 5%。
[0164] 化合物的核
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