一种区域选择性合成茚-吲哚衍生物的方法与流程

1.本发明属于有机合成领域,具体涉及一种吲哚c2和c3区域选择性合成茚-吲哚衍生物的方法。。


背景技术：

2.取代茚及其相关的茚酮衍生物是众多天然产物中的重要结构单元，如乙酰胆碱酶抑制剂donepezil、内皮素受体拮抗剂enrasentan、抗炎sulindac、醛固酮合酶抑制剂和抗结核药物等。茚及茚酮衍生物也是药物合成、天然产品和其他生物活性化合物的关键中间体(eur j med chem 138,182-198(2017).)。茚-吲哚衍生物存在于天然产物和多种生物活性的药物中，发现吲哚c2和c3区域选择性合成茚-吲哚衍生物的方法非常关键。此外，吲哚c3位置是亲电取代反应最活跃的位置，然而c2位置官能团化需要导向基团的协助，且需要相对昂贵的贵金属催化剂如铑、钌和钯等来实现。已报道的合成方法仍然面临着一定的局限性，包括难以控制的区域选择性、氧化剂化学计量的使用等不足(angew.chem.,int.ed. 2015,54,11956.)。因此，开发茚-吲哚类化合物的区域选择性合成新方法具有极高的价值。
[0003][0004]
茚及其衍生物在药物化学中是重要的生物活性分子，已被研究具有优异的生物活性，包括治疗阿尔茨海默病和抗癌活性等。例如，没食子酸茚酮及其2
‑ꢀ
苄叉茚二酮衍生物(1)是芳香化酶的抑制剂，具有抑制乳腺癌的活性(med.chem. res.2011,20,661-669.)；indanocine(2)具有抗耐药性恶性肿瘤的增殖活性(natl.cancer inst.2000,92,217-224.)；多奈哌齐(3)作为乙酰胆碱酯酶抑制剂被fda批准用于治疗轻度至中度阿尔茨海默病(curr.med.chem. 2000,3,303-339.)。


技术实现要素：

[0005]
由于取代茚及其相关的茚酮衍生物结构在药物化学中的重要性，本发明提供一种利用富电子芳基烯基-1，3-二噻烷区域选择性合成茚-吲哚衍生物的方法，该方法克服现有方法的不足，本方法操作简单易行，具用原料廉价易得，产物容易分离纯化和环境绿色友好的特点。
[0006]
一种区域选择性合成茚-吲哚衍生物的方法，其特征在于：在路易斯酸、氧化剂或质子酸作用下，n-取代吲哚化合物和富电子芳基烯基-1，3-二噻烷，在适当反应溶剂和温度下发生偶联反应，区域选择性的生成茚-吲哚类衍生物，如下式：
r1为吲哚2-7位取代基，选自c1-6烷基、c1-6烷氧基、c1-2卤代烷基、卤素、硝基、氰基、乙酰基、卞氧基、甲砜基、氨基、羧基、羟基、羟甲基、酯基；r2为吲哚1位取代基，选自氢、甲基、对甲苯磺酰基、叔丁氧羰基、苄基；n-取代吲哚化合物包括色胺、褪黑素、色胺酸衍生物、氮杂吲哚吲哚；x为为cl,br,i,otf基团；富电子芳基烯基-1，3-二噻烷取代基，选自3,4,5-三甲氧基苯基、3,4-二甲氧基苯基、 2,5-二甲氧基苯基、富电子杂环(吲哚、吡咯、呋喃和吡啶)、3,5-二甲氧基苯基、萘基、亚甲二氧基苯基。
[0007]
一种区域选择性合成茚-吲哚衍生物的方法，其特征在于：路易斯酸选自三氯化铟、三溴化铟、三碘化铟、三氯化铁、六水合三氯化铁、三氟化硼乙醚中的一种或多种；氧化剂为ncs、碘单质、nbs、dtbp中的一种；质子酸为三氟甲磺酸、磷酸、亚磷酸中的一种或多种。
[0008]
一种区域选择性合成茚-吲哚衍生物的方法，其特征在于：所使用的溶剂为甲苯、 1,2-二氯甲烷、1,2-二氯乙烷、三氯甲烷、硝基甲烷的一种或数种。
[0009]
一种区域选择性合成茚-吲哚衍生物的方法，其特征在于：所述的操作步骤中所使用的反应物的摩尔比为富电子芳基烯基-1，3-二噻烷:吲哚＝1:(0.5-3.0)。
[0010]
所述的一种区域选择性合成茚-吲哚衍生物的方法，其特征在于：反应温度范围为0-100℃。
具体实施方式：
[0012]
下面结合具体实施例对本发明做出进一步地详细阐述,所述实施例只用于解释本发明,并非用于限定本发明的范围。下述实施例中所使用的试验方法如无特殊说明,均为常规方法:所使用的材料、试剂等,如无特殊说明,为可从商业途径得到的试剂和材料。
[0013]
具体实施的例的产物结构如下：
[0014]
3,4,5-三甲氧基苯基茚-吲哚类化合物的合成过程如下:
[0015]
具体步骤如下：在10毫升圆底烧瓶中，加入吲哚类化合物(0.25mmol)和3,4,5
‑ꢀ
三甲氧基苯基-β-氯-乙烯-1，3-二噻烷(69mg，0.2mmol)，用6毫升溶剂溶解后加入催化剂铟(ⅲ)(0.03mmol)，在室温下搅拌反应24-48h，tlc检测直至原料消失，将反应到入10ml冰水中，并用乙酸乙酯(15ml)萃取3次，合并有机相，并用15ml饱和碳酸氢钠和食盐水洗涤。有机相经过无水硫酸钠干燥后过滤，所得滤液在减压条件下旋干,剩余的油状物经过快速柱层析分离，得到相应的3,4,5-三甲氧基苯基茚-吲哚类化合物。
[0016]
所述吲哚类化合物
[0017]
当r1为氢时，所用催化剂为inbr3，所用溶剂为二氯甲烷，所得化合物为mp1；
[0018]
当r1为5-氟时，所用催化剂为inbr3，所用溶剂为二氯乙烷，所得化合物为mp2；
[0019]
当r1为5-氯时，所用催化剂为inbr3，所用溶剂为三氯甲烷，所得化合物为mp3；
[0020]
当r1为6-氯时，所用催化剂为inbr3，所用溶剂为甲苯，所得化合物为mp4；
[0021]
当r1为4-溴时，所用催化剂为incl3，所用溶剂为二氯乙烷，所得化合物为mp5；
[0022]
当r1为5-溴时，所用催化剂为ini3，所用溶剂为二氯乙烷，所得化合物为mp6；
[0023]
当r1为7-溴时，所用催化剂为碘单质，所用溶剂为二氯乙烷，所得化合物为mp7；
[0024]
当r1为5-氰基时，所用催化剂为ncs，所用溶剂为二氯乙烷，所得化合物为mp8；
[0025]
当r1为5-硝基时所用催化剂为incl3，所用溶剂为二氯乙烷，，所得化合物为mp9；
[0026]
当r1为5-卞氧基时，所用催化剂为inbr3，所用溶剂为二氯乙烷，所得化合物为mp10；
[0027]
当r1为5-甲氧基时，所用催化剂为inbr3，所用溶剂为二氯甲烷，所得化合物为mp11；
[0028]
当r1为5甲基时，所用催化剂为inbr3，所用溶剂为二氯乙烷，所得化合物为mp12；
[0029]
当r1为5,6-亚甲二氧基时，所用催化剂为inbr3，所用溶剂为二氯乙烷，所得化合物为mp13；
[0030]
当r2为1-甲基时，所用催化剂为incl3，所用溶剂为二氯乙烷，所得化合物为mp14；
[0031]
当r2为1-对甲苯磺酸基时，所用催化剂为incl3，所用溶剂为二氯乙烷，所得化合物为mp15；
[0032]
当r1为3-甲基时，所用催化剂为incl3，所用溶剂为二氯乙烷，所得化合物为mp16；
[0033]
当r1为3-乙酸甲酯时，所用催化剂为incl3，所用溶剂为二氯乙烷，所得化合物为 mp17；
[0034]
当r1为3-乙酸时，所用催化剂为inbr3，所用溶剂为二氯乙烷，所得化合物为mp18；
[0035]
当r1为3-乙醇时，所用催化剂为inbr3，所用溶剂为二氯乙烷，所得化合物为mp19；
[0036]
当r1为3-乙酰乙胺基时，所用催化剂为inbr3，所用溶剂为二氯乙烷，所得化合物为mp20；
[0037]
当r1为3-乙基乙酰氨基丙酸时，所用催化剂为inbr3，所用溶剂为二氯乙烷，所得化合物为mp21；
[0038]
化合物mp1-mp18的核磁数据如下：
[0039]
1、化合物mp1
[0040][0041]1h nmr(400mhz,chloroform-d)δ8.77(s,1h),7.55(d,j＝7.5hz,1h),7.24(d,j＝ 7.7hz,1h),7.13
–
7.00(m,2h),6.92(s,1h),6.45(s,1h),4.85(dd,j＝9.4,3.7hz,1h),3.91(s, 3h),3.82(s,3h),3.43(s,3h),3.43
–
3.35(m,1h),3.27
–
3.13(m,3h),2.97
–
2.87(m,2h),2.31
ꢀ–
2.20(m,1h),2.11
–
1.98(m,1h).
13
c nmr(101mhz,cdcl3)δ154.88,150.21,143.41,141.05, 139.54,136.28,128.63,128.50,121.19,120.12,119.50,110.81,103.61,100.16,60.90,60.72,58.82, 56.39,50.74,40.98,29.78,29.30,24.90.
[0042]
2、化合物mp2
[0043][0044]1h nmr(400mhz,chloroform-d)δ8.81(s,1h),7.25(s,1h),7.18(dd,j＝9.8,2.5hz, 1h),7.13(dd,j＝8.8,4.6hz,1h),6.91(s,1h),6.87
–
6.77(m,1h),6.43
–
6.36(m,1h),4.82(dd, j＝9.4,3.7hz,1h),3.91(s,3h),3.82(s,3h),3.46(s,3h),3.39(dd,j＝13.9,9.4hz,1h),3.26
–ꢀ
3.14(m,3h),2.92(d,j＝15.0hz,2h),2.28
–
2.20(m,1h),2.09
–
2.00(m,1h).
13
c nmr(101 mhz,cdcl3)δ159.04,156.72,154.92,150.08,143.33,142.97,139.48,132.72,128.80,128.70, 128.37,111.29,111.20,109.44,109.18,105.01,104.78,103.58,100.34,100.29,60.89,60.69,58.76, 56.36,50.56,40.95,29.79,29.24,24.84.
[0045]
3、化合物mp3
[0046][0047]1h nmr(400mhz,chloroform-d)δ8.87(s,1h),7.50(d,j＝2.0hz,1h),7.14(d,j＝ 8.5hz,1h),7.02(dd,j＝8.6,2.1hz,1h),6.91(s,1h),6.39(d,j＝1.8hz,1h),4.82(dd,j＝9.4, 3.6hz,1h),3.91(s,3h),3.82(s,3h),3.45(s,3h),3.38(dd,j＝13.9,9.4hz,1h),3.22(dd,j＝ 13.9,3.6hz,3h),2.92(d,j＝13.0hz,2h),2.28
–
2.18(m,1h),2.09
–
1.99(m,1h).
13
c nmr (101mhz,cdcl3)δ154.87,149.99,143.24,142.58,139.45,134.50,129.47,128.22,124.97, 121.30,119.39,111.71,103.53,99.79,60.81,60.61,58.68,56.28,
50.46,40.81,29.68,29.16,24.76.
[0048]
4、化合物mp4
[0049][0050]1h nmr(400mhz,chloroform-d)δ8.85(s,1h),7.43(d,j＝8.4hz,1h),7.24(s,1h), 7.01(dd,j＝8.4,1.9hz,1h),6.91(s,1h),6.41(s,1h),4.82(dd,j＝9.4,3.6hz,1h),3.91(s,3h), 3.82(s,3h),3.46(s,3h),3.38(dd,j＝13.9,9.4hz,1h),3.26
–
3.14(m,3h),2.93(d,j＝14.2hz, 1h),2.29
–
2.19(m,1h),2.06(t,j＝13.3hz,1h).
13
c nmr(101mhz,cdcl3)δ154.91,150.04, 143.30,141.85,139.45,136.54,128.25,126.97,126.88,120.83,120.12,110.76,103.57,100.10, 60.85,60.65,58.71,56.33,50.49,40.83,29.73,29.19,24.79.
[0051]
5、化合物mp5
[0052][0053]1h nmr(400mhz,chloroform-d)δ9.00(s,1h),7.17(dd,j＝16.4,7.9hz,2h),6.95
–ꢀ
6.88(m,2h),6.50(d,j＝2.1hz,1h),4.83(dd,j＝9.2,3.9hz,1h),3.88(s,3h),3.81(s,3h), 3.46(s,3h),3.37(dd,j＝13.9,9.3hz,1h),3.21
–
3.09(m,3h),2.88(d,j＝14.5hz,2h),2.24
–ꢀ
2.14(m,1h),2.04
–
1.95(m,1h).
13
c nmr(101mhz,cdcl3)δ154.83,149.98,143.16,141.76, 139.49,136.25,129.05,128.00,122.26,121.99,113.81,109.92,103.46,100.31,60.79,60.59,58.59, 56.25,50.50,40.76,29.57,29.14,24.71.
[0054]
6、化合物mp6
[0055][0056]1h nmr(400mhz,chloroform-d)δ8.91(s,1h),7.65(s,1h),7.14(dd,j＝8.6,1.9hz, 1h),7.08(d,j＝8.6hz,1h),6.91(s,1h),6.38(s,1h),4.81(dd,j＝9.3,3.7hz,1h),3.88(s,3h), 3.81(s,3h),3.44(s,3h),3.36(dd,j＝13.9,9.3hz,1h),3.22
–
3.10(m,3h),2.89(d,j＝14.6hz, 2h),2.29
–
2.07(m,1h),2.07
–
1.94(m,1h).
13
c nmr(101mhz,cdcl3)δ154.82,149.94, 143.18,142.40,139.41,134.72,130.10,128.16,123.81,122.42,112.54,112.17,103.47,99.64, 60.80,60.59,58.64,56.25,50.41,40.73,29.65,29.12,24.72.
[0057]
7、化合物mp7
[0058][0059]1h nmr(400mhz,chloroform-d)δ9.33(s,1h),7.47(d,j＝7.8hz,1h),7.22(d,j＝ 7.7hz,1h),6.96
–
6.87(m,2h),6.51(d,j＝2.2hz,1h),4.84(dd,j＝9.2,3.5hz,1h),3.91(s, 3h),3.82(s,3h),3.54(s,3h),3.40
–
3.35(m,1h),3.32
–
3.13(m,3h),2.94(t,j＝15.2hz,2h), 2.33
–
2.15(m,1h),2.08
–
1.98(m,1h).
13
c nmr(101mhz,cdcl3)δ154.92,150.04,143.24, 141.74,139.30,135.11,129.51,128.24,123.43,120.59,119.20,104.28,103.54,101.13,60.84, 60.73,58.74,56.34,50.13,40.79,29.72,29.14,24.75.
[0060]
8、化合物mp8
[0061][0062]1h nmr(400mhz,chloroform-d)δ9.26(s,1h),7.88(s,1h),7.37
–
7.27(m,2h),6.92 (s,1h),6.52(s,1h),4.86(dd,j＝9.4,3.3hz,1h),3.91(s,3h),3.82(s,3h),3.51(s,3h),3.43
–ꢀ
3.34(m,1h),3.31
–
3.15(m,3h),3.02
–
2.89(m,2h),2.33
–
2.22(m,1h),2.12
–
1.99(m,1h). 13
c nmr(101mhz,cdcl3)δ155.16,149.96,143.60,143.31,139.47,137.95,128.20,127.78, 125.59,124.37,121.07,111.64,103.66,102.56,100.72,60.93,60.74,58.74,56.40,50.27,40.76, 29.91,29.17,24.79.
[0063]
9、化合物mp9
[0064][0065]1h nmr(400mhz,chloroform-d)δ9.38(s,1h),8.50(d,j＝2.2hz,1h),8.01(dd,j＝ 8.9,2.2hz,1h),7.26(d,j＝8.8hz,1h),6.92(s,1h),6.62(s,1h),4.87(dd,j＝9.4,3.2hz,1h), 3.92(s,3h),3.82(s,3h),3.53(s,3h),3.41(dd,j＝14.0,9.4hz,1h),3.33
–
3.18(m,3h),2.97 (dd,j＝9.2,5.3hz,2h),2.32
–
2.23(m,1h),2.13
–
2.00(m,1h).
13
c nmr(101mhz,cdcl3)δ 155.19,149.92,144.56,143.28,141.74,139.43,139.34,127.71,127.65,117.30,117.13,110.68, 103.63,102.19,60.93,60.76,58.73,56.40,50.10,40.79,29.95,29.14,24.76.
[0066]
10、化合物mp10
[0067]
[0068]1h nmr(400mhz,chloroform-d)δ8.65(s,1h),7.50
–
7.43(m,2h),7.42
–
7.33(m, 2h),7.31(d,j＝7.3hz,1h),7.13(d,j＝8.7hz,1h),7.10(d,j＝2.4hz,1h),6.91(s,1h),6.83 (dd,j＝8.7,2.4hz,1h),6.36(s,1h),5.08(s,2h),4.82(dd,j＝9.4,3.7hz,1h),3.91(s,3h),3.82 (s,3h),3.45(s,3h),3.39(dd,j＝13.9,9.4hz,1h),3.26
–
3.14(m,3h),2.96
–
2.86(m,2h),2.25 (d,j＝14.7hz,1h),2.08
–
1.96(m,1h).
13
c nmr(101mhz,cdcl3)δ154.86,153.30,150.18, 143.39,141.94,139.51,137.98,131.63,128.90,128.65,128.57,127.78,127.63,111.91,111.43, 103.84,103.59,100.10,70.99,60.92,60.75,58.81,56.40,50.73,41.03,29.80,29.31,24.90.
[0069]
11、化合物mp11
[0070][0071]1h nmr(400mhz,chloroform-d)δ8.65(s,1h),7.12(d,j＝8.8hz,1h),7.02(d,j＝ 2.4hz,1h),6.91(s,1h),6.74(dd,j＝8.7,2.5hz,1h),6.37(d,j＝2.0hz,1h),4.81(dd,j＝9.3, 3.8hz,1h),3.90(s,3h),3.82(d,j＝3.0hz,6h),3.44(s,3h),3.38(dd,j＝13.9,9.3hz,1h), 3.23
–
3.13(m,3h),2.94
–
2.83(m,2h),2.27
–
2.17(m,1h),2.07
–
1.95(m,1h).
13
c nmr(101 mhz,cdcl3)δ154.80,154.01,150.14,143.34,141.87,139.49,131.38,128.88,128.64,111.40, 111.08,103.55,102.18,100.02,60.87,60.69,58.77,56.35,55.91,50.72,40.99,29.73,29.27,24.86.
[0072]
12、化合物mp12
[0073][0074]1h nmr(400mhz,chloroform-d)δ8.69
–
8.57(m,1h),7.33(s,1h),7.13(d,j＝8.2 hz,1h),6.93
–
6.83(m,2h),6.36(d,j＝1.2hz,1h),4.83(dd,j＝9.3,3.8hz,1h),3.91(s,3h), 3.82(s,3h),3.42(s,3h),3.40
–
3.33(m,1h),3.24
–
3.14(m,3h),2.95
–
2.87(m,2h),2.41(s, 3h),2.28
–
2.19(m,1h),2.06
–
2.00(m,1h).
13
c nmr(101mhz,cdcl3)δ154.76,150.16, 143.33,139.49,134.52,128.72,128.68,128.56,122.68,119.78,110.41,103.51,99.65,60.84,60.66, 58.76,56.32,50.73,40.96,29.67,29.24,24.84,21.50.
[0075]
13、化合物mp13
[0076][0077]1h nmr(400mhz,chloroform-d)δ8.65(s,1h),6.92(d,j＝7.4hz,2h),6.72(s,1h), 6.30(s,1h),5.87(s,2h),4.78(dd,j＝9.3,3.8hz,1h),3.91(s,3h),3.82(s,3h),
3.45(s,3h), 3.37(dd,j＝13.9,9.3hz,1h),3.24
–
3.13(m,3h),2.92(d,j＝14.4hz,2h),2.29
–
2.19(m,1h), 2.08
–
1.98(m,1h).
13
c nmr(101mhz,cdcl3)δ154.77,150.13,144.16,143.37,142.62,139.42, 130.93,128.75,122.13,103.57,100.39,98.89,92.05,60.88,60.71,58.75,56.35,50.73,40.97, 29.74,29.28,24.88.
[0078]
14、化合物mp14
[0079][0080]1h nmr(400mhz,chloroform-d)δ7.42(d,j＝7.9hz,1h),7.28(d,j＝8.3hz,1h), 7.19(t,j＝7.0hz,1h),7.03(t,j＝7.5hz,1h),6.94(s,1h),6.89(s,1h),4.87(t,j＝7.7hz,1h), 3.93(s,3h),3.80(s,3h),3.73(s,3h),3.52(dd,j＝13.3,8.1hz,1h),3.24(s,3h),3.23
–
3.16(m, 1h),3.11
–
3.03(m,1h),2.99(dd,j＝13.3,7.3hz,1h),2.92
–
2.77(m,2h),2.23
–
2.14(m,1h), 2.07
–
1.95(m,1h).
13
c nmr(101mhz,cdcl3)δ154.02,150.43,142.89,140.00,137.23,129.74, 126.98,126.56,121.34,119.44,118.61,117.23,109.21,103.17,60.81,60.00,58.61,56.25,56.21, 52.49,38.61,32.68,29.96,28.90,25.07.
[0081]
15、化合物mp15
[0082][0083]1h nmr(400mhz,chloroform-d)δ8.00(d,j＝8.2hz,1h),7.75(d,j＝8.4hz,2h), 7.38(s,1h),7.29
–
7.23(m,2h),7.13(t,j＝7.6hz,2h),6.93(s,1h),4.74(t,j＝7.7hz,1h), 3.93(s,3h),3.77(s,3h),3.42(dd,j＝13.3,8.2hz,1h),3.22
–
3.11(m,1h),3.01(s,4h),2.92
–ꢀ
2.84(m,2h),2.78(d,j＝14.1hz,1h),2.32(s,3h),2.22
–
2.11(m,1h),2.03
–
1.94(m,1h).
13
c nmr(101mhz,cdcl3)δ154.45,150.08,144.67,142.79,140.09,135.57,135.37,130.02,129.67, 128.01,126.84,125.18,124.51,123.46,122.96,120.05,113.85,103.21,60.72,59.69,58.44,56.23, 51.06,38.24,29.80,28.80,24.88,21.52.
[0084]
16、化合物mp16
[0085][0086]1h nmr(400mhz,chloroform-d)δ8.63(s,1h),7.55
–
7.48(m,1h),7.21
–
7.14(m, 1h),7.10
–
7.01(m,2h),6.92(s,1h),4.95(dd,j＝9.7,3.3hz,1h),3.91(s,3h),3.80(s,
3h), 3.40(dd,j＝14.0,9.7hz,1h),3.30(s,3h),3.21
–
3.12(m,3h),2.92(dd,j＝14.2,3.9hz,2h), 2.40(s,3h),2.27
–
2.18(m,1h),2.08
–
2.00(m,1h).
13
c nmr(101mhz,cdcl3)δ154.72, 150.04,143.37,139.14,136.15,135.36,129.24,128.95,121.11,118.71,118.31,110.55,106.91, 103.39,60.76,60.23,59.02,56.26,50.56,38.26,29.78,29.15,24.78,8.68.
[0087]
17、化合物mp17
[0088][0089]1h nmr(400mhz,chloroform-d)δ8.77(s,1h),7.60
–
7.52(m,1h),7.20
–
7.18(m, 1h),7.11
–
7.06(m,2h),6.92(s,1h),4.98(dd,j＝9.8,3.1hz,1h),4.00
–
3.84(m,5h),3.79(s, 3h),3.71(s,3h),3.44(dd,j＝14.2,9.8hz,1h),3.32(s,3h),3.24
–
3.13(m,2h),2.99
–
2.88(m, 2h),2.29
–
2.18(m,1h),2.09
–
2.00(m,1h).
13
c nmr(101mhz,cdcl3)δ172.68,154.94, 150.04,143.25,139.34,138.29,135.28,128.62,128.07,121.48,119.39,118.43,110.86,104.20, 103.36,60.80,60.31,59.03,56.31,51.97,50.53,38.40,30.10,29.84,29.11,24.78.
[0090]
18、化合物mp18
[0091][0092]1h nmr(400mhz,chloroform-d)δ8.82(s,1h),7.57
–
7.54(m,1h),7.21
–
7.15(m, 1h),7.09
–
7.05(m,2h),6.91(s,1h),4.94(dd,j＝9.7,3.2hz,1h),4.03
–
3.85(m,5h),3.77(s, 3h),3.40(dd,j＝14.2,9.7hz,1h),3.33(s,3h),3.19
–
3.10(m,3h),2.87(d,j＝14.7hz,2h), 2.23
–
2.15(m,1h),2.04
–
1.92(m,1h).
13
c nmr(101mhz,cdcl3)δ178.25,154.93,149.90, 143.13,139.32,138.43,135.26,128.40,127.91,121.62,119.48,118.39,110.90,103.51,103.36, 60.77,60.33,58.96,56.28,50.48,38.31,30.16,29.76,29.06,24.71.
[0093]
19、化合物mp19
[0094][0095]1h nmr(400mhz,chloroform-d)δ8.37(s,1h),7.55(d,j＝6.8hz,1h),7.21(d,j＝ 7.1hz,1h),7.13
–
7.05(m,2h),6.94(s,1h),5.04(dd,j＝9.5,4.3hz,1h),3.93(s,5h),3.79
(s, 3h),3.43(dd,j＝13.9,9.5hz,1h),3.31(s,3h),3.21
–
3.10(m,4h),3.03(dd,j＝13.9,4.3hz, 1h),2.95
–
2.83(m,2h),2.43(s,1h),2.23(d,j＝14.2hz,1h),2.09
–
1.98(m,1h).
13
c nmr (101mhz,cdcl3)δ154.96,149.81,143.15,139.87,138.21,135.71,128.19,128.16,121.59, 119.24,118.30,110.82,108.17,103.54,63.15,60.82,60.41,58.86,56.34,51.13,38.36,29.59, 29.35,27.91,24.82.
[0096]
20、化合物mp20
[0097][0098]1h nmr(400mhz,chloroform-d)δ8.43(d,j＝2.6hz,1h),7.55(d,j＝7.1hz,1h), 7.20(d,j＝6.4hz,1h),7.14
–
7.04(m,2h),6.96(s,1h),6.42(s,1h),4.91(dd,j＝9.0,5.4hz, 1h),3.92(s,4h),3.79(s,3h),3.48
–
3.33(m,2h),3.26(s,3h),3.18
–
3.07(m,3h),3.01
–
2.92 (m,2h),2.92
–
2.85(m,2h),2.27
–
2.15(m,1h),2.06
–
1.95(m,1h),1.88(s,3h).
13
c nmr(101 mhz,cdcl3)δ170.30,154.95,149.64,143.23,140.15,137.25,135.63,128.05,127.91,121.65, 119.35,118.22,110.76,109.05,103.78,60.77,60.29,58.66,56.33,51.17,40.21,38.31,29.49, 29.33,24.76,24.27,22.98.
[0099]
21、化合物mp21
[0100][0101]1h nmr(400 mhz,chloroform-d)δ8.34(s,1h),7.55(d,j＝7.9 hz,1h),7.21(d,j＝ 9.0 hz,1h),7.17(d,j＝8.0 hz,1h),7.06(t,j＝7.5 hz,1h),7.02
–
6.95(m,1h),6.95(s,1h), 5.15(dt,j＝8.8,4.6 hz,1h),4.87(dd,j＝9.0,5.5 hz,1h),3.93(s,3h),3.79(s,3h),3.62(dd,j＝15.0,3.6 hz,1h),3.45
–
3.30(m,2h),3.27(s,3h),3.14(d,j＝12.2 hz,2h),2.94
–
2.82(m, 3h),2.22(d,j＝14.1 hz,1h),2.02(t,j＝13.3 hz,1h),1.87(s,3h).
13
c nmr(101 mhz,cdcl3) δ175.26,170.86,155.11,149.51,143.38,140.34,138.47,135.47,128.76,127.92,121.92,119.72, 118.60,110.67,105.93,103.88,60.83,60.61,58.74,56.42,52.72,51.21,38.66,29.80,29.57,29.38, 26.65,24.83,22.80。