取代的雷帕霉素三氮唑衍生物和用途转让专利
申请号 : CN201410547357.1
文献号 : CN104341434B
文献日 : 2016-04-06
发明人 : 黄捷 , 谢立君 , 程元荣 , 李邦良 , 潘福生 , 李夸良 , 余辉 , 应加银 , 杨国新 , 金东伟 , 郑从燊 , 吕裕斌
申请人 : 福建省微生物研究所
摘要 :
权利要求 :
1.以下式I化合物:
或其药学可接受的盐、异构体,其中,
n为1、2或3;
X为 或“—”;
R为氢、甲基、或(C1-C4)烷基;
R1为(C1-C4)烷基氨基甲基-、苯胺基甲基-、或苯基-,其中苯基或者苯胺基甲基-上的苯环任选被1-4个相同或不同的R2基团取代;
R2选自:氢、羟基、卤素、三氟甲基、三氟甲氧基、氨基、羧基、氰基、(C1-C4)烷基、(C1-C6)烷基、(C1-C4)烷氧基、N-(C1-C4)烷基氨基、N,N-二(C1-C4)烷基氨基、(C1-C4)烷基硫基、(C1-C4)烷基亚磺酰基、(C1-C4)烷基磺酰基、(C1-C4)烷氧基甲基、(C1-C4)烷氧基乙基、(C1-C4)烷基酰基、氨基甲酰基、N-(C1-C4)烷基氨基甲酰基、N,N-二(C1-C4)烷基氨基甲酰基、(C1-C3)亚烷基二氧基。
2.权利要求1的化合物,其中所述(C1-C4)烷基选自甲基、乙基、丙基、异丙基、正丁基、异丁基、叔丁基。
3.权利要求1的化合物,其中所述卤素选自氟、氯、溴、碘。
4.权利要求1的化合物,其中R为氢、或甲基。
5.权利要求1的化合物,其中X为 n为1。
6.权利要求1的化合物,其中X为单键,n为2或3。
7.权利要求1的化合物,其为选自下列的化合物或其药学可接受的盐、异构体:
43-O-(2-(4-(4-氟苯基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-(4-氯苯基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-(4-甲基苯基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-(苯基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-(4-戊基苯基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-(3-甲基苯基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-(2-氯苯基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-(4-溴苯基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-(4-甲氧基苯基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-((2,5二氯苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-((2,4二氯苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-((2,6二氟苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(2-(4-((2-氟苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)乙基)氧雷帕霉素
43-O-(3-(4-(4-氟苯基)-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(3-(4-(4-氯苯基)-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(3-(4-(4-甲基苯基)-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(3-(苯基-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(3-(4-(3-甲基苯基)-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(3-(4-(2-氯苯基)-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(3-(4-(4-溴苯基)-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(3-(4-(4-甲氧基苯基)-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(3-(4-((2,5二氯苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(3-(4-((2,4二氯苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(3-(4-((2,6二氟苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(3-(4-((2-氟苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)正丙基)氧雷帕霉素
43-O-(2-(4-(4-氟苯基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-(4-氯苯基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-(4-甲基苯基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-(苯基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-(4-戊基苯基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-(3-甲基苯基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-(2-氯苯基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-(4-溴苯基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-(4-甲氧基苯基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-((2,5二氯苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-((2-氟苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-(吡咯烷基-1-亚甲基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-(二乙氨基甲基)-1H-1,2,3-三氮唑-1-基)乙酰基)氧雷帕霉素
43-O-(2-(4-(4-氟苯基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素
43-O-(2-(4-(4-氯苯基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素
43-O-(2-(4-(4-甲基苯基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素
43-O-(2-(4-(苯基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素
43-O-(2-(4-(4-戊基苯基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素
43-O-(2-(4-(3-甲基苯基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素
43-O-(2-(4-(2-氯苯基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素
43-O-(2-(4-(4-溴苯基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素
43-O-(2-(4-(4-甲氧基苯基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素
43-O-(2-(4-((2,5二氯苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素
43-O-(2-(4-((2,4二氯苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素
43-O-(2-(4-((2-氟苯基)氨基甲基)-1H-1,2,3-三氮唑-1-基)异丙酰基)氧雷帕霉素。
8.一种药物组合物,其包括权利要求1-7任一项的化合物,以及任选的药学可接受的载体或辅料。
9.权利要求1-7任一项的化合物在制备用于预防或治疗肿瘤和/或癌症的药物中的用途。
10.权利要求9的用途,所述肿瘤和/或癌症选自:肺癌、胰腺癌、食道癌、胃癌、宫颈癌、前列腺癌、白血病、肾癌。
11.制备权利要求1-7任一项的化合物的方法,其包括以下步骤:从以下化合物A-1 : 制备得到以 下式 A-2化合物:接着使A-2化合物与R1芳基取代的炔类化合物经五水硫酸酮和抗坏血酸钠反应得到式I化合物:任选地使式I化合物形成其药学可接受的盐、异构体;其中各取代基如权利要求1-7任一项所述。
12.权利要求11的方法,当X为“—”,R为氢时,A-2化合物的制备方法为:以A-1化合物为原料,与B-1所示三氟甲磺酸酯即 化合物侧链反应得到B-2化合物:接着使B-2化合物与叠氮化钠反应得到A-2化合物。
13.权利要求11的方法,当X为 时,A-2化合物的制备方法为:以A-1化合物为原料与三甲基氯硅烷反应 ,得到以下式C-1化合物:接着使C-1化合物与式 的C-2化合物酯化,得到以下式C-3化合物:接着使C-3化合物与叠氮化钠反应得到C-4化合物:最后使C-4化合物脱保护得到A-2化合物。
说明书 :
取代的雷帕霉素三氮唑衍生物和用途
技术领域
2009年抗肿瘤用药市场达523.72亿美元,仅次于心血管疾病的用药。目前临床应用的传统抗癌药物主要有植物碱类、烷化剂类、抗生素类和激素类,绝大部分是细胞毒药物,选择性低、毒副作用很大,且易产生耐药性,疗效受到明显影响。因此开发新的高效低毒的抗癌靶向药物已成为抗肿瘤药物研发的趋势。近年来,分子靶向药物因具有针对性强、切实有效且毒副反应低等优点,已成为国内外肿瘤治疗领域研发的热点。其中哺乳动物雷帕霉素靶位(mammalian target of rapamycin,mTOR)为最新发现的癌症治疗靶位。
发明内容
测定方法为:将约25mg的测试物料精确称重并置于样品盘中,将其暴露于相对湿度0~90%的湿度环境中;在0~15%RH范围内采用1%RH梯度进行详细分析、在15~90%RH范围内采用15%RH梯度进行详细分析;分析温度为30℃,氮气流速为200立方厘米/min;得到各化合物的吸湿等温线。结果显示,本发明全部化合物在0%-90%RH的范围内只吸收了低于0.3%(w/w)的水,而雷帕霉素和替西罗莫司吸水均大于0.8%,表明本发明化合物是不吸湿的,这是一种优良的原料药性质。
具体实施方式
)。H NMR(500MHz,DMSO)δ8.53(s,1H),7.87(dd,J=8.7,5.5Hz,2H),7.28(t,J=8.9Hz,
2H),6.45(s,1H),6.43-6.32(m,1H),6.26-6.17(m,1H),6.16-6.06(m,2H),5.45(dd,J=
14.8,9.7Hz,1H),5.26(d,J=4.5Hz,1H),5.09(d,J=10.2Hz,1H),4.99-4.95(m,1H),4.94-
4.89(m,1H),4.53(m,1H),4.06-3.87(m,4H),3.62(m,1H),3.47-3.38(m,1H),3.29-3.23(m,
1H),3.21(s,3H),3.14(s,3H),3.05(s,3H),3.02-2.93(m,2H),2.83-2.75(m,1H),2.75-
2.68(m,1H),2.43-2.33(m,2H),2.25-2.15(m,1H),2.10(m,1H),2.06-1.95(m,1H),1.93-
1.77(m,2H),1.73(s,3H),1.62(s,3H),1.55(d,J=39.0Hz,3H),1.45-1.00(m,9H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.5Hz,3H),0.81(d,J=6.4Hz,3H),0.76(d,J=6.7Hz,3H),0.72
13
(d,J=6.5Hz,3H)。CNMR(126MHz,DMSO)δ210.46,207.50,198.90,169.19,166.97,145.21,
139.28,137.83,137.13,132.32,130.42,127.48,127.03,126.97,124.89,121.61,115.87,
115.70,99.00,85.51,82.38,82.23,82.15,75.73,73.60,67.64,66.18,56.91,56.64,
55.45,50.73,50.22,45.18,43.47,38.16,35.62,35.16,34.79,33.33,32.13,30.79,
29.62,29.47,26.41,26.21,24.44,21.63,20.35,15.55,15.52,14.66,13.41,13.35,
10.44。
1H),5.26(s,1H),5.09(d,J=10.2Hz,1H),4.99-4.95(m,1H),4.95-4.90(m,1H),4.56-4.51(m,2H),4.03-3.88(m,5H),3.63-3.59(m,1H),3.46-3.40(m,1H),3.29-3.22(m,1H),3.20(s,3H),3.14(s,3H),3.05(s,3H),3.01-2.90(m,2H),2.86-2.68(m,2H),2.44-2.34(m,2H),
2.25-2.16(m,1H),2.13-2.05(m,1H),2.05-1.95(m,2H),1.94-1.77(m,3H),1.73(s,3H),
1.62(s,3H),1.59-1.00(m,10H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.5Hz,3H),0.81(d,J=6.4Hz,3H),0.76(d,J=6.7Hz,3H),0.72(d,J=6.6Hz,3H).13C NMR(126MHz,DMSO)δ
210.46,207.50,198.90,169.18,166.97,144.99,139.28,137.83,137.13,132.32,132.12,
130.42,129.81,128.93,126.98,126.70,124.90,122.05,99.00,85.51,82.37,82.23,
82.15,75.73,73.60,67.61,66.18,56.91,56.63,55.45,50.72,50.26,45.18,43.48,
38.15,35.61,35.16,34.79,33.33,32.12,30.79,29.62,29.48,26.40,26.21,24.44,
21.63,20.36,15.55,15.52,14.66,13.40,13.35,10.44。
)。H NMR(500MHz,DMSO)δ8.48(s,1H),7.71(d,J=8.0Hz,2H),7.25(d,J=7.9Hz,2H),6.45(s,1H),6.38(m,1H),6.27-6.16(m,1H),6.17-6.06(m,2H),5.45(dd,J=13.8,10.8Hz,1H),
5.26(s,1H),5.09(d,J=10.4Hz,1H),4.97(m,1H),4.93(m,1H),4.59-4.46(m,2H),4.05-
3.86(m,4H),3.62(m,1H),3.50-3.39(m,1H),3.29-3.23(m,1H),3.21(s,3H),3.14(s,3H),
3.05(s,1H),2.85-2.75(m,1H),2.76-2.68(m,1H),2.43-2.34(m,2H),2.33(s,3H),2.28-
2.15(m,1H),2.10(m,2H),2.06-1.95(m,1H),1.96-1.78(m,2H),1.73(s,3H),1.62(s,3H),
1.61-1.01(m,9H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.4Hz,3H),0.81(d,J=6.3Hz,3H),
0.76(d,J=6.6Hz,3H),0.73(d,J=6.5Hz,3H)。13C NMR(126MHz,DMSO)δ210.46,207.51,
198.90,169.18,166.97,146.13,139.28,137.83,137.13,136.96,132.32,130.42,129.40,
128.15,127.00,124.95,121.26,99.00,85.51,82.36,82.24,82.12,75.72,73.61,67.63,
66.19,56.91,56.64,55.45,50.73,50.13,45.19,43.48,38.15,35.61,35.16,34.79,
33.34,32.13,30.81,29.57,29.46,26.41,26.22,24.44,21.64,20.79,20.36,15.56,
15.52,14.66,13.40,13.36,10.45。
5.25(s,1H),5.09(d,J=9.9Hz,1H),4.97(m,1H),4.93(m,1H),4.59-4.47(m,2H),4.06-
3.87(m,4H),3.62(m,1H),3.43(m,3.6Hz,1H),3.30-3.23(m,1H),3.21(s,3H),3.14(s,3H),
3.05(s,3H),3.02-2.93(m,2H),2.84-2.76(m,1H),2.72(m,1H),2.44-2.31(m,2H),2.22(m,
1H),2.15-2.06(m,1H),2.05-1.96(m,1H),1.94-1.77(m,2H),1.73(s,3H),1.62(s,3H),
1.60-1.00(m,10H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.4Hz,3H),0.81(d,J=6.3Hz,2H),
13
0.76(d,J=6.7Hz,2H),0.73(d,J=6.5Hz,3H)。C NMR(126MHz,DMSO)δ210.46,207.50,
198.90,169.19,166.97,146.07,139.29,137.83,137.13,132.32,130.91,130.42,128.86,
127.70,126.98,125.01,121.68,99.00,85.51,82.37,82.23,82.13,75.72,73.61,67.63,
66.18,56.91,56.64,55.45,50.73,50.18,45.19,43.48,38.15,35.61,35.16,34.79,
33.34,32.13,30.81,29.62,29.46,26.41,26.21,24.44,21.63,20.36,15.56,15.52,
14.66,13.40,13.36,10.45。
9.7Hz,1H),5.26(d,J=4.3Hz,1H),5.09(m,1H),5.00-4.95(m,1H),4.93m,1H),4.56-4.48(m,2H),4.04-3.90(m,4H),3.62(m,1H),3.47-3.40(m,1H),3.21(s,3H),3.14(s,3H),3.05(s,3H),3.02-2.92(m,2H),2.83-2.77(m,1H),2.75-2.68(m,1H),2.59(m,2H),2.43-2.33(m,2H),2.26-2.17(m,1H),2.10(m,1H),2.05-1.96(m,1H),1.94-1.77(m,3H),1.73(s,3H),
1.62(s,3H),1.59-1.00(m,15H),0.97(d,J=6.3Hz,3H),0.87(s,6H),0.81(d,J=5.9Hz,
4H),0.76(d,J=6.5Hz,3H),0.73(d,J=6.3Hz,3H)。13C NMR(126MHz,DMSO)δ210.44,
207.49,198.89,169.17,166.96,146.15,141.91,139.27,137.82,137.12,132.31,130.41,
128.72,128.37,126.97,124.97,121.27,98.99,85.50,82.36,82.23,82.12,75.71,73.60,
67.64,66.18,56.89,56.63,55.43,50.71,50.13,45.18,43.46,38.15,35.60,35.15,
34.81,33.33,32.12,30.83,30.49,29.61,29.55,29.45,26.39,26.20,24.44,21.91,
21.62,20.35,15.54,15.50,14.65,13.87,13.38,13.35,10.44。
7.6Hz,1H),7.14(d,J=7.6Hz,1H),6.45(s,1H),6.43-6.33(m,1H),6.25-6.17(m,1H),
6.16-6.07(m,2H),5.45(dd,J=14.9,9.6Hz,1H),5.26(s,1H),5.09(d,J=10.2Hz,1H),
5.01-4.95(m,1H),4.93(t,J=5.9Hz,1H),4.56-4.48(m,2H),4.03-3.89(m,5H),3.66-3.58(m,1H),3.47-3.39(m,1H),3.28-3.24(m,1H),3.22(s,3H),3.14(s,3H),3.05(s,3H),3.02-
2.94(m,2H),2.84-2.68(m,2H),2.44-2.37(m,2H),2.35(s,3H),2.24-2.20(m,1H),2.13-
2.04(m,1H),2.04-1.95(m,2H),1.94-1.77(m,3H),1.73(s,3H),1.62(s,3H),1.59-1.01(m,
10H),0.97(d,J=6.5Hz,3H),0.87(d,J=6.5Hz,3H),0.81(d,J=6.4Hz,3H),0.76(d,J=
13
6.7Hz,3H),0.73(d,J=6.6Hz,3H)。CNMR(126MHz,DMSO)δ210.46,207.50,198.90,197.22,
169.18,166.97,146.16,139.28,137.96,137.82,137.13,132.32,130.83,130.42,128.75,
128.34,126.99,125.56,124.91,122.19,121.60,99.00,85.52,82.35,82.24,82.12,
75.72,73.61,67.60,66.19,56.91,56.63,55.45,50.72,50.15,45.19,43.48,38.16,
35.60,35.16,34.79,33.34,32.30,32.13,30.81,29.62,29.57,29.45,26.40,26.21,
24.44,21.63,21.03,20.36,15.55,15.52,14.66,13.39,13.37,10.45。
7.43(m,1H),7.42-7.36(m,1H),6.45(s,1H),6.43-6.33(m,1H),6.25-6.17(m,1H),6.16-
6.04(m,2H),5.45(dd,J=14.8,9.7Hz,2H),5.26(s,1H),5.08(d,J=10.2Hz,1H),4.99-
4.95(m,1H),4.95-4.91(m,1H),4.62-4.56(m,2H),4.03-3.90(m,5H),3.65-3.58(m,1H),
3.47-3.40(m,1H),3.29-3.23(m,1H),3.20(s,3H),3.14(s,3H),3.05(s,3H),2.99-2.92(m,
2H),2.83-2.69(m,2H),2.43-2.33(m,2H),2.26-2.15(m,1H),2.13-2.06(m,1H),2.05-1.95(m,2H),1.94-1.78(m,3H),1.73(s,3H),1.62(s,3H),1.59-1.00(m,10H),0.97(d,J=
6.5Hz,3H),0.87(d,J=6.5Hz,3H),0.81(d,J=6.4Hz,3H),0.76(d,J=6.7Hz,3H),0.72(d,J=6.7Hz,3H)。13C NMR(126MHz,DMSO)δ210.51,207.49,198.93,169.17,166.97,142.38,
139.29,137.82,137.15,132.31,130.41,130.20,129.45,129.34,129.31,127.50,126.98,
124.98,124.62,110.94,99.00,85.54,82.45,82.25,82.13,75.70,73.61,67.72,66.19,
56.93,56.65,55.45,50.69,50.22,45.18,43.46,38.14,35.59,35.17,34.79,33.35,
32.12,30.82,29.57,29.52,26.41,26.21,24.44,21.64,20.35,15.55,15.51,14.65,
13.41,13.34,10.45。
1H),5.26(s,1H),5.08(d,J=10.2Hz,1H),4.99-4.95(m,1H),4.95-4.90(m,1H),4.57-4.50(m,2H),4.05-3.89(m,5H),3.64-3.59(m,1H),3.46-3.40(m,1H),3.29-3.23(m,1H),3.20(s,3H),3.14(s,3H),3.05(s,3H),3.01-2.90(m,2H),2.83-2.68(m,2H),2.45-2.33(m,2H),
2.25-2.16(m,1H),2.13-2.07(m,1H),2.06-1.94(m,2H),1.94-1.77(m,3H),1.73(s,3H),
1.62(s,3H),1.58-1.01(m,10H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.5Hz,3H),0.81(d,J
13
=6.4Hz,3H),0.76(d,J=6.7Hz,3H),0.72(d,J=6.6Hz,3H). C NMR(126MHz,DMSO)δ
210.46,207.50,198.90,188.64,169.18,166.97,145.02,139.28,137.83,137.13,132.32,
131.84,130.42,130.16,126.99,124.89,122.07,120.64,99.00,85.50,82.37,82.23,
82.14,75.72,73.60,67.60,66.18,56.91,56.63,55.45,50.73,50.27,45.19,43.47,
38.15,35.61,35.16,34.79,33.33,32.12,30.79,29.57,29.47,26.40,26.21,24.44,
21.64,20.36,15.56,15.52,14.66,13.40,13.36,10.45。
9.6Hz,1H),5.27(s,1H),5.12-5.06(m,1H),5.01-4.94(m,1H),4.95-4.90(m,1H),4.56-
4.47(m,2H),4.04-3.88(m,4H),3.79(s,3H),3.65-3.58(m,1H),3.47-3.40(m,1H),3.40-
3.29(m,2H),3.22(s,3H),3.14(s,3H),3.05(s,3H),2.83-2.76(m,1H),2.74-2.71(m,1H),
2.43-2.33(m,2H),2.25-2.17(m,1H),2.14-2.05(m,1H),2.05-1.96(m,2H),1.94-1.77(m,
3H),1.73(s,3H),1.62(s,3H),1.56-1.00(m,10H),0.98(d,J=6.4Hz,3H),0.87(d,J=
6.4Hz,3H),0.82(d,J=6.3Hz,3H),0.76(d,J=6.6Hz,3H),0.73(d,J=6.5Hz,3H)。13C NMR(126MHz,DMSO)δ210.46,207.50,198.90,169.19,166.97,158.88,146.01,139.29,137.83,
137.13,132.32,130.42,126.98,126.35,124.90,123.52,120.73,114.27,99.00,85.50,
82.37,82.24,82.13,75.72,73.61,67.66,66.19,56.91,56.66,55.45,55.10,50.73,
50.11,45.19,43.48,38.17,35.62,35.16,34.79,33.34,32.14,30.81,29.56,26.40,
26.21,24.45,21.63,20.36,15.56,15.52,14.66,13.40,13.36,10.45。
1H),4.96-4.91(m,1H),4.49-4.38(m,4H),4.04-3.97(m,2H),3.95-3.92(m,1H),3.88-3.84(m,2H),3.65-3.59(m,1H),3.48-3.39(m,1H),3.15(s,3H),3.13(s,3H),3.05(s,3H),2.89-
2.82(m,1H),2.75-2.69(m,1H),2.44-2.34(m,2H),2.27-2.16(m,1H),2.13-2.05(m,2H),
2.06-1.94(m,1H),1.92-1.79(m,3H),1.74(s,3H),1.63(s,3H),1.61-1.03(m,9H),0.98(d,J=6.3Hz,3H),0.87(d,J=6.4Hz,3H),0.83(d,J=6.2Hz,3H),0.77(d,J=6.6Hz,3H),0.73
13
(d,J=6.5Hz,3H)。C NMR(126MHz,DMSO)δ210.49,207.49,198.90,169.19,166.97,
144.81,144.66,139.31,137.84,137.13,132.48,132.33,130.42,129.99,126.99,124.91,
123.12,116.46,115.93,110.84,99.00,85.52,82.43,82.24,81.92,75.74,73.62,67.65,
66.19,56.93,56.57,55.45,50.74,49.97,45.20,43.48,38.09,35.58,35.17,34.79,
33.38,32.14,30.82,29.63,29.38,26.42,26.23,24.45,21.64,20.36,15.57,15.53,
14.70,13.40,10.46。
6.16-6.05(m,2H),5.46(dd,J=14.8,9.7Hz,1H),5.25(s,1H),5.12-5.06(m,1H),5.00-
4.95(m,1H),4.95-4.90(m,1H),4.46-4.38(m,4H),4.05-3.97(m,2H),3.95-3.90(m,1H),
3.87-3.79(m,2H),3.65-3.59(m,1H),3.47-3.39(m,1H),3.15(s,3H),3.13(s,3H),3.05(s,
3H),3.02-2.95(m,2H),2.89-2.78(m,1H),2.75-2.68(m,2H),2.44-2.34(m,1H),2.28-2.17(m,1H),2.13-2.06(m,2H),2.06-1.96(m,2H),1.91-1.79(m,2H),1.73(s,3H),1.63(s,3H),
1.61-1.00(m,9H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.4Hz,3H),0.83(d,J=6.3Hz,3H),
0.77(d,J=6.5Hz,3H),0.73(d,J=6.6Hz,3H)。13CNMR(126MHz,DMSO)δ210.99,207.99,
199.39,169.69,167.48,145.35,143.29,139.82,138.36,137.63,132.85,130.94,128.61,
128.14,125.46,123.59,119.67,118.87,113.02,100.00,99.51,86.06,82.94,82.77,
82.46,76.26,74.16,68.18,66.72,57.46,57.09,55.97,51.27,50.48,45.71,43.98,
38.81,36.12,35.67,35.30,33.91,32.71,31.33,30.15,29.90,28.28,26.94,26.74,
24.97,22.15,20.88,16.07,16.06,15.24,13.93,13.90,10.99。
5.59-5.51(m,1H),5.46(dd,J=14.9,9.6Hz,1H),5.27(s,1H),5.13-5.06(m,1H),5.02-
4.96(m,1H),4.96-4.90(m,1H),4.47-4.38(m,4H),4.05-3.97(m,2H),3.97-3.92(m,1H),
3.89-3.79(m,2H),3.65-3.59(m,1H),3.47-3.40(m,1H),3.32(s,3H),3.16(s,3H),3.05(s,
3H),2.91-2.83(m,2H),2.77-2.69(m,1H),2.44-2.35(m,2H),2.28-2.18(m,1H),2.15-2.06(m,2H),2.05-1.98(m,2H),1.92-1.79(m,3H),1.74(s,3H),1.63(s,3H),1.58-1.01(m,
10H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.5Hz,3H),0.83(d,J=6.3Hz,4H),0.78(d,J=
6.6Hz,3H),0.73(d,J=6.6Hz,3H)。13CNMR(126MHz,DMSO)δ210.46,207.51,198.88,169.22,
166.97,145.86,139.30,137.84,137.11,132.34,130.42,126.99,124.88,122.73,116.86,
111.70,111.52,99.00,85.50,82.46,82.24,81.97,75.74,73.58,67.79,66.19,56.92,
56.56,55.45,50.75,49.88,45.20,43.48,40.47,38.14,35.63,35.17,34.79,33.35,
32.11,30.78,29.57,29.42,26.42,26.22,24.45,21.63,20.35,15.57,15.54,14.70,
13.44,13.36,10.46。
6.36(m,1H),6.27-6.18(m,2H),5.95(m,1H),5.46(dd,J=14.9,9.6Hz,1H),5.29(s,1H),
5.08(d,J=10.0Hz,1H),4.99-4.95(m,1H),4.97-4.91(m,1H),4.43(m,2H),4.36(s,2H),
4.06-3.98(m,2H),3.96(m,1H),3.90-3.76(m,4H),3.63(m,1H),3.48-3.39(m,1H),3.29-
3.21(m,1H),3.15(s,3H),3.14(s,3H),3.05(s,3H),2.93-2.83(m,1H),2.77-2.68(m,1H),
2.45-2.31(m,2H),2.29-2.16(m,1H),2.10(m,1H),2.05-1.96(m,1H),1.90-1.79(m,3H),
1.74(s,3H),1.63(s,3H),1.60-1.00(m,10H),0.98(d,J=6.6Hz,3H),0.86(d,J=6.5Hz,
3H),0.82(d,J=6.4Hz,3H),0.77(d,J=6.8Hz,3H),0.73(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ210.47,207.55,198.93,169.24,167.00,151.88,149.99,145.47,139.33,
137.87,137.15,136.30,136.20,132.36,130.46,127.05,124.85,124.59,123.06,115.72,
115.67,114.28,114.13,112.25,99.03,85.48,82.40,82.25,81.98,75.76,73.60,67.71,
66.20,56.93,56.60,55.49,50.78,49.92,45.23,43.51,38.18,35.64,35.20,34.82,
33.37,32.12,30.80,29.63,29.40,29.01,26.45,26.24,24.49,21.66,20.40,15.62,
15.54,14.70,13.51,13.33,10.48。
干得油状物,经柱层析分离分别得到2.4g,收率:52%。MS(ESI)m/z:1019.6(M+Na)。
2H),6.44(s,1H),6.41-6.32(m,1H),6.26-6.18(m,1H),6.17-6.08(m,2H),5.51-5.42(m,
1H),5.25(s,1H),5.10(d,J=10.2Hz,1H),5.02-4.97(m,1H),4.97-4.91(m,1H),4.50-4.43(m,2H),4.06-3.98(m,2H),3.97-3.91(m,1H),3.67-3.58(m,1H),3.57-3.42(m,3H),3.34(s,3H),3.16(s,3H),3.05(s,3H),2.90-2.65(m,2H),2.45-2.34(m,2H),2.28-2.17(m,1H),
2.14-2.03(m,2H),2.01-1.90(m,2H),1.89-1.78(m,2H),1.74(s,3H),1.64(s,3H),1.60-
1.04(m,10H),0.98(d,J=6.3Hz,3H),0.88(d,J=6.3Hz,3H),0.83(d,J=6.1Hz,3H),0.78
13
(d,J=6.4Hz,3H),0.74(d,J=6.4Hz,3H)。C NMR(126MHz,DMSO)δ210.43,207.48,198.85,
169.18,166.96,162.64,160.70,145.34,139.27,137.82,137.10,132.31,130.40,127.43,
127.06,126.99,124.90,121.29,115.82,115.65,98.98,85.51,82.42,82.23,81.97,
75.73,73.59,66.18,65.45,56.91,56.88,55.43,50.74,46.84,45.18,43.46,38.21,
35.82,35.14,34.77,33.34,32.23,30.83,30.36,29.61,29.52,26.40,26.21,24.43,
21.61,20.33,15.52,14.69,13.39,13.36,10.44。
1H),5.26(s,1H),5.10(d,J=10.1Hz,1H),5.01-4.96(m,1H),4.96-4.91(m,1H),4.50-4.42(m,2H),4.06-3.98(m,2H),3.97-3.93(m,1H),3.65-3.60(m,1H),3.58-3.38(m,3H),3.33(s,3H),3.29-3.22(m,1H),3.16(s,3H),3.05(s,3H),2.87-2.69(m,2H),2.44-2.33(m,2H),
2.27-2.17(m,1H),2.13-2.01(m,2H),2.00-1.91(m,2H),1.90-1.79(m,2H),1.75(s,3H),
1.63(s,3H),1.60-1.02(m,10H),0.98(d,J=6.6Hz,3H),0.87(d,J=6.5Hz,3H),0.82(d,J=6.5Hz,3H),0.78(d,J=6.7Hz,3H),0.73(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ
210.43,207.51,198.88,169.20,166.98,145.13,139.28,137.84,137.12,132.33,132.15,
130.42,129.77,128.91,127.01,126.73,124.87,121.77,99.00,85.50,82.43,82.23,
81.98,75.74,73.60,66.19,65.46,56.91,55.46,50.76,46.91,45.19,43.49,38.23,
35.82,35.16,34.79,33.34,32.22,30.84,30.35,29.63,29.54,26.42,26.23,24.45,
21.63,20.36,15.57,15.53,14.69,13.44,13.34,10.46。
5.30(s,1H),5.02-4.96(m,1H),4.94(m,1H),4.49-4.40(m,1H),4.06-3.97(m,2H),3.98-
3.92(m,1H),3.66-3.57(m,1H),3.57-3.40(m,3H),3.30-3.23(m,1H),3.34(s,3H),3.15(s,
3H),3.05(s,3H),2.85-2.78(m,1H),2.77-2.68(m,1H),2.43-2.34(m,1H),2.33(s,3H),
2.27-2.17(m,1H),2.14-2.00(m,2H),2.00-1.87(m,2H),1.89-1.79(m,2H),1.75(s,3H),
1.63(s,3H),1.60-1.02(m,10H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.5Hz,3H),0.82(d,J=6.4Hz,3H),0.78(d,J=6.6Hz,3H),0.73(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ
210.46,207.56,198.93,169.24,167.01,146.30,139.31,137.88,137.17,137.03,132.35,
130.47,129.42,128.12,127.03,125.01,124.86,121.04,99.04,85.48,82.45,82.25,
82.03,75.76,73.61,66.20,65.49,56.95,55.49,50.78,46.80,45.23,43.52,38.24,
35.86,35.20,34.83,33.36,32.22,30.88,30.41,29.55,26.45,26.24,24.48,21.65,
20.83,20.40,15.62,15.54,14.70,13.51,13.32,10.48。
3.99(m,2H),3.96(d,J=4.2Hz,1H),3.66-3.59(m,1H),3.57-3.41(m,3H),3.34(s,3H),
3.27(m,1H),3.15(s,3H),3.05(s,3H),2.86-2.77(m,1H),2.77-2.69(m,1H),2.43-2.33(m,
2H),2.22(m,1H),2.14-1.99(m,2H),2.01-1.88(m,2H),1.89-1.79(m,2H),1.75(s,3H),
1.63(s,3H),1.60-1.00(m,10H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.4Hz,3H),0.82(d,J=6.4Hz,3H),0.78(d,J=6.5Hz,3H),0.73(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ
210.45,207.56,198.92,169.24,167.01,146.24,139.31,137.88,137.16,132.35,130.88,
130.47,128.88,127.77,127.03,125.07,121.46,110.97,99.03,85.48,82.45,82.24,
82.03,75.76,73.61,66.20,65.48,56.95,55.49,50.78,46.84,45.23,43.52,38.25,
35.85,35.20,34.83,33.37,32.22,30.87,30.41,29.63,29.56,26.44,26.25,24.48,
21.66,20.41,15.62,15.55,14.71,13.51,13.32,10.48。
7.6Hz,1H),7.14(d,J=7.6Hz,1H),6.45(s,1H),6.44-6.33(m,1H),6.27-6.17(m,1H),
6.17-6.07(m,2H),5.46(dd,J=14.8,9.7Hz,1H),5.27(s,1H),5.02-4.96(m,1H),4.96-
4.92(m,1H),4.50-4.41(m,2H),4.06-3.97(m,2H),4.00-3.90(m,1H),3.67-3.59(m,1H),
3.58-3.41(m,3H),3.34(s,3H),3.16(s,3H),3.05(s,3H),2.85-2.69(m,2H),2.45-2.37(m,
2H),2.35(s,3H),2.27-2.18(m,1H),2.13-2.02(m,3H),1.97-1.90(m,2H),1.89-1.78(m,
2H),1.74(s,3H),1.63(s,3H),1.60-1.02(m,10H),0.98(d,J=6.5Hz,3H),0.87(d,J=
6.5Hz,3H),0.83(d,J=6.4Hz,3H),0.78(d,J=6.6Hz,3H),0.74(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ210.44,198.89,169.20,166.98,146.31,139.29,137.95,137.84,137.13,
132.33,130.78,130.43,128.73,128.37,127.01,125.63,124.89,122.23,121.35,99.00,
85.51,82.43,82.24,81.99,75.74,73.60,66.19,65.47,56.91,55.45,50.75,46.80,
45.20,43.49,38.22,35.82,35.17,34.80,33.35,32.23,30.85,30.36,29.54,26.42,
26.22,24.45,21.63,21.03,15.57,15.53,14.70,13.43,13.35,10.45。
7.47-7.43(m,1H),7.42-7.35(m,1H),6.45(s,1H),6.43-6.34(m,1H),6.26-6.18(m,1H),
6.17-6.08(m,2H),5.46(dd,J=14.8,9.7Hz,1H),5.27(s,1H),5.09(d,J=10.2Hz,1H),
5.01-4.95(m,1H),4.94-4.92(m,1H),4.55-4.49(m,2H),4.05-3.98(m,2H),3.96-3.91(m,
1H),3.66-3.58(m,1H),3.57-3.39(m,3H),3.33(s,3H),3.30-3.23(m,1H),3.15(s,3H),
3.05(s,3H),2.84-2.70(m,2H),2.47-2.35(m,2H),2.25-2.17(m,1H),2.14-2.04(m,3H),
2.02-1.90(m,2H),1.89-1.79(m,2H),1.74(s,3H),1.63(s,3H),1.60-1.01(m,10H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.5Hz,3H),0.82(d,J=6.4Hz,3H),0.78(d,J=6.7Hz,3H),
0.73(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ210.47,207.50,198.90,169.18,166.97,
142.46,139.28,137.83,137.13,132.31,130.41,130.26,130.16,129.46,129.32,127.47,
127.00,124.92,124.41,110.92,98.99,85.51,82.41,82.24,82.04,75.72,73.60,66.18,
65.39,56.90,55.44,50.72,46.81,45.18,43.47,38.19,35.79,35.16,34.79,33.34,
32.21,30.86,30.40,29.52,26.41,26.21,24.44,21.62,20.35,15.55,15.52,14.68,
13.37,10.45。
)。H NMR(500MHz,DMSO)δ8.63(s,1H),7.79(d,J=8.2Hz,2H),7.64(d,J=8.2Hz,2H),6.46(s,1H),6.44-6.34(m,1H),6.27-6.19(m,1H),6.17-6.08(m,2H),5.46(dd,J=14.7,9.6Hz,
1H),5.27(s,1H),5.13-5.07(m,1H),5.02-4.96(m,1H),4.97-4.91(m,1H),4.52-4.42(m,
2H),4.06-3.97(m,2H),3.98-3.91(m,1H),3.63(m,1H),3.57-3.40(m,3H),3.33(s,3H),
3.16(s,3H),3.05(s,3H),2.86-2.68(m,2H),2.44-2.34(m,2H),2.25-2.18(m,1H),2.14-
2.01(m,3H),1.98-1.90(m,2H),1.89-1.79(m,2H),1.75(s,3H),1.63(s,3H),1.60-1.02(m,
10H),0.98(d,J=6.4Hz,3H),0.87(d,J=6.3Hz,3H),0.83(d,J=6.3Hz,3H),0.78(d,J=
6.4Hz,3H),0.73(d,J=6.5Hz,3H)。13C NMR(126MHz,DMSO)δ210.43,207.51,198.88,
169.21,166.98,145.16,139.29,137.84,137.12,132.33,131.82,130.42,130.12,127.02,
124.88,121.80,120.68,99.00,85.50,82.43,82.23,81.98,75.74,73.60,66.19,65.46,
56.91,55.46,50.75,46.91,45.20,43.49,38.23,35.83,35.17,34.79,33.34,32.23,
30.84,30.34,29.64,29.54,26.42,26.23,24.45,21.63,20.37,15.57,15.53,14.70,
13.44,13.34,10.46。
14.8,9.6Hz,1H),5.28(s,1H),5.10(d,J=10.2Hz,1H),5.02-4.96(m,1H),4.96-4.92(m,
1H),4.48-4.37(m,2H),4.06-3.97(m,2H),3.97-3.89(m,1H),3.79(s,3H),3.66-3.59(m,
1H),3.58-3.39(m,3H),3.34(s,3H),3.16(s,3H),3.05(s,3H),2.85-2.68(m,1H),2.44-
2.34(m,2H),2.29-2.14(m,1H),2.15-2.01(m,3H),2.01-1.89(m,2H),1.89-1.77(m,2H),
1.75(s,3H),1.63(s,3H),1.62-1.03(m,10H),0.98(d,J=6.6Hz,3H),0.87(d,J=6.5Hz,
3H),0.83(d,J=6.5Hz,3H),0.78(d,J=6.7Hz,3H),0.74(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ210.44,207.51,198.88,169.20,166.98,158.90,146.15,139.29,137.84,
137.13,132.33,130.42,127.01,126.38,124.88,123.47,120.45,114.25,99.00,85.50,
82.43,82.23,82.00,75.74,73.60,66.19,65.48,56.92,55.45,55.10,50.75,46.74,
45.20,43.49,38.23,35.83,35.16,34.79,33.35,32.23,30.86,30.40,29.64,29.54,
26.42,26.23,24.45,21.63,20.37,15.57,15.52,14.70,13.44,13.34,10.46。
6.16-6.09(m,2H),5.47(dd,J=14.9,9.6Hz,1H),5.26(s,1H),5.13-5.07(m,1H),5.03-
4.96(m,1H),4.97-4.90(m,1H),4.47-4.35(m,4H),4.07-3.92(m,3H),3.66-3.59(m,1H),
3.49-3.39(m,2H),3.29(s,3H),3.16(s,3H),3.05(s,3H),2.98-2.89(m,2H),2.87-2.77(m,
1H),2.77-2.68(m,1H),2.46-2.35(m,2H),2.28-2.18(m,1H),2.16-2.06(m,1H),2.06-1.96(m,3H),1.94-1.79(m,3H),1.74(s,3H),1.63(s,3H),1.60-1.00(m,10H),0.98(d,J=
6.5Hz,3H),0.88(d,J=6.5Hz,3H),0.83(d,J=6.4Hz,3H),0.78(d,J=6.7Hz,3H),0.74(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ210.44,207.47,198.85,169.19,166.95,144.83,
144.72,139.28,137.82,137.10,132.44,132.32,130.00,126.96,124.89,122.85,116.50,
115.96,110.87,98.98,85.51,82.33,82.24,81.96,75.73,73.59,66.31,66.18,65.27,
56.92,56.82,55.44,50.75,46.53,45.19,43.46,38.22,35.74,35.15,34.77,33.36,
32.22,30.81,30.38,29.62,29.43,26.41,26.22,24.44,21.61,20.34,15.55,15.52,
14.73,13.40,13.37,10.45。
6.18-6.05(m,2H),5.51-5.41(m,1H),5.26(s,1H),5.10(d,J=9.6Hz,1H),5.02-4.96(m,
1H),4.96-4.93(m,1H),4.43(s,2H),4.41-4.32(m,2H),4.05-3.97(m,2H),3.94(m,1H),
3.66-3.59(m,1H),3.49-3.38(m,3H),3.29(s,3H),3.16(s,3H),3.05(s,3H),2.97-2.86(m,
2H),2.84-2.66(m,2H),2.44-2.34(m,2H),2.28-2.15(m,1H),2.14-2.00(m,2H),2.01-1.93(m,2H),1.93-1.79(m,2H),1.74(s,3H),1.63(s,3H),1.60-1.02(m,11H),0.98(d,J=
6.4Hz,3H),0.87(d,J=6.5Hz,3H),0.83(d,J=6.5Hz,3H),0.78(d,J=6.6Hz,3H),0.73(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ210.42,207.46,198.84,169.18,166.95,144.92,
142.79,139.27,137.82,137.09,132.31,130.39,128.12,127.60,126.95,124.88,122.83,
119.14,118.38,112.45,98.98,85.50,82.32,82.23,81.95,75.73,73.57,66.17,65.26,
56.91,56.80,55.43,50.75,46.48,45.18,43.46,38.40,38.19,35.73,35.14,34.77,
33.37,32.22,30.77,30.36,29.42,26.41,26.22,24.43,21.61,20.34,15.55,15.52,
14.75,13.40,13.36,10.45。
6.70-6.60(m,1H),6.44(s,1H),6.41-6.32(m,1H),6.28-6.17(m,1H),6.18-6.07(m,2H),
5.53-5.42(m,2H),5.26(s,1H),5.10(d,J=9.9Hz,1H),5.03-4.97(m,1H),4.96(m,1H),
4.45(s,2H),4.38-4.33(m,2H),4.05-3.98(m,2H),3.98-3.92(m,1H),3.67-3.60(m,1H),
3.48-3.36(m,3H),3.31(s,3H),3.16(s,3H),3.05(s,3H),2.99-2.93(m,2H),2.86-2.78(m,
1H),2.76-2.70(m,1H),2.46-2.35(m,2H),2.27-2.17(m,1H),2.15-2.02(m,2H),1.99-1.89(m,2H),1.89-1.78(m,2H),1.75(s,3H),1.64(s,3H),1.58-1.01(m,10H),0.98(d,J=
6.4Hz,3H),0.88(d,J=6.4Hz,3H),0.83(d,J=6.4Hz,3H),0.78(d,J=6.6Hz,3H),0.74(d,J=6.5Hz,3H)。
1H),6.44-6.34(m,1H),6.26-6.18(m,1H),6.17-6.08(m,2H),5.90(s,1H),5.51-5.43(m,
1H),5.28(s,1H),5.10(d,J=10.2Hz,1H),5.01-4.96(m,1H),4.97-4.90(m,1H),4.41-4.31(m,4H),4.05-3.97(m,2H),3.98-3.92(m,1H),3.66-3.58(m,1H),3.49-3.35(m,3H),3.32(s,3H),3.16(s,3H),3.05(s,3H),3.00-2.89(m,2H),2.85-2.69(m,2H),2.43-2.34(m,2H),
2.27-2.17(m,1H),2.15-2.02(m,2H),2.02-1.93(m,2H),1.93-1.79(m,2H),1.75(s,3H),
1.63(s,3H),1.62-1.02(m,10H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.4Hz,3H),0.83(d,J=6.3Hz,3H),0.78(d,J=6.6Hz,3H),0.74(d,J=6.5Hz,3H)。13C NMR(126MHz,DMSO)δ
210.43,207.51,198.87,169.21,166.97,145.50,139.30,137.84,137.12,136.30,136.21,
132.33,130.42,127.02,124.86,124.56,122.79,115.71,114.28,114.14,112.22,99.00,
85.49,82.36,82.23,81.96,75.75,73.59,66.19,65.35,56.91,56.87,55.46,50.77,
46.50,45.20,43.49,38.26,35.79,35.17,34.79,33.36,32.21,30.81,30.44,29.63,
29.57,29.47,26.43,26.23,24.46,21.63,20.36,15.57,15.53,14.72,13.46,13.34,
10.46。
100mL水中,乙酸乙酯提取2次,合并提取液,水洗,无水硫酸钠干燥。蒸干得油状物,经柱层析分离分别得到0.6g,收率为33%。MS(ESI)m/z:1019.5(M+Na)+。
6.43-6.35(m,1H),6.26-6.18(m,1H),6.17-6.09(m,2H),5.51-5.43(m,2H),5.29(s,1H),
5.10(d,J=9.9Hz,1H),5.00-4.96(m,1H),4.96-4.92(m,1H),4.70-4.60(m,1H),4.05-3.98(m,2H),3.99-3.93(m,1H),3.66-3.58(m,1H),3.48-3.38(m,1H),3.27(s,3H),3.16(s,3H),
3.05(s,3H),2.86-2.69(m,2H),241–2.37(m,2H),2.26-2.16(m,1H),2.14-2.06(m,2H),
2.07-1.89(m,3H),1.87-1.77(m,2H),1.75(s,3H),1.63(s,3H),1.60-1.03(m,10H),0.98(d,J=6.3Hz,3H),0.87(d,J=6.4Hz,3H),0.82(d,J=6.3Hz,3H),0.78(d,J=6.5Hz,3H),
0.73(d,J=6.3Hz,3H)。13C NMR(126MHz,DMSO)δ210.38,207.53,198.86,169.22,166.99,
166.70,160.82,145.48,139.31,137.86,137.15,132.34,130.41,127.21,127.14,127.09,
126.99,124.81,122.66,115.94,115.77,99.01,85.46,82.22,79.85,77.74,75.73,73.65,
66.19,56.89,56.76,55.45,50.78,50.67,45.23,43.50,38.01,35.16,34.80,33.32,
31.87,30.43,29.65,29.14,26.40,26.23,24.44,21.62,20.37,15.52,14.63,13.50,
13.29,10.45。
6.44(s,1H),6.43-6.35(m,1H),6.26-6.17(m,1H),6.16-6.07(m,2H),5.47(s,2H),5.26(s,
1H),5.10(d,J=10.0Hz,1H),5.01-4.96(m,1H),4.95-4.90(m,1H),4.70-4.58(m,1H),
4.06-3.97(m,2H),3.98-3.90(m,1H),3.66-3.58(m,1H),3.48-3.40(m,1H),3.27(s,3H),
3.16(s,3H),3.05(s,3H),2.86-2.68(m,2H),2.44-2.33(m,2H),2.28-2.18(m,1H),2.15-
2.07(m,2H),2.07-1.97(m,2H),1.96-1.79(m,3H),1.74(s,3H),1.63(s,3H),1.60-1.03(m,
10H),0.98(d,J=6.3Hz,3H),0.87(d,J=6.4Hz,3H),0.82(d,J=6.3Hz,3H),0.78(d,J=
6.5Hz,3H),0.73(d,J=6.3Hz,3H)。13C NMR(126MHz,DMSO)δ210.38,207.49,198.83,
169.19,166.97,166.63,145.25,139.29,137.83,137.12,132.34,130.38,129.41,128.95,
126.96,126.83,124.84,123.07,98.98,85.48,82.22,79.85,77.74,75.71,73.64,66.18,
56.89,56.73,55.42,50.76,50.68,45.21,43.47,37.98,35.27,35.14,34.78,33.32,
31.88,30.42,29.64,29.54,29.12,26.39,26.21,24.42,21.60,20.34,15.52,15.50,
14.63,13.45,13.32,10.43。
3H),5.29(s,1H),5.10(d,J=10.0Hz,1H),5.00-4.96(m,1H),4.96-4.92(m,1H),4.69-4.60(m,1H),4.05-3.99(m,2H),3.98-3.92(m,1H),3.66-3.58(m,1H),3.49-3.39(m,1H),3.27(s,3H),3.16(s,3H),3.05(s,3H),2.86-2.69(m,2H),2.42-2.35(m,2H),2.33(s,3H),2.24-
2.21(m,1H),2.16-2.07(m,2H),2.05-1.96(m,2H),1.97-1.78(m,2H),1.75(s,3H),1.63(s,
3H),1.61-1.02(m,10H),0.98(d,J=6.4Hz,3H),0.87(d,J=6.4Hz,3H),0.82(d,J=6.3Hz,
3H),0.78(d,J=6.5Hz,3H),0.73(d,J=6.4Hz,3H)。13C NMR(126MHz,DMSO)δ210.39,
207.54,198.86,169.22,166.99,166.75,146.39,139.31,137.86,137.23,132.34,130.41,
129.46,127.76,127.00,125.07,124.81,122.33,110.93,99.01,85.46,82.22,79.86,
77.72,75.72,73.66,66.18,56.89,56.77,55.45,50.78,50.62,45.23,43.49,37.99,
35.27,35.16,34.80,33.33,31.87,30.45,29.66,29.57,29.14,26.41,26.22,24.45,
21.63,20.80,20.38,15.56,15.52,14.62,13.50,13.30,10.45。
5.47(s,2H),5.31(s,1H),5.14-5.04(m,1H),5.01-4.90(m,2H),4.71-4.59(m,1H),4.06-
3.93(m,3H),3.67-3.58(m,1H),3.51-3.39(m,1H),3.27(s,3H),3.15(s,3H),3.05(s,3H),
2.86-2.68(m,2H),2.43-2.30(m,2H),2.28-2.16(m,1H),2.16-2.07(m,1H),2.06-1.96(m,
2H),1.96-1.78(m,3H),1.75(s,3H),1.63(s,3H),1.58-1.02(m,10H),0.98(d,J=6.5Hz,
3H),0.86(d,J=6.5Hz,3H),0.82(d,J=6.4Hz,3H),0.78(d,J=6.6Hz,3H),0.73(d,J=
6.5Hz,3H)。13C NMR(101MHz,DMSO)δ210.90,208.05,199.37,169.72,167.49,167.23,
146.84,139.82,138.36,137.65,132.85,131.02,130.91,129.43,128.43,127.50,125.64,
125.32,123.26,99.51,85.97,82.72,80.36,78.24,76.23,74.17,66.69,57.40,57.27,
55.96,51.28,51.16,45.73,44.01,38.49,35.78,35.67,35.30,33.83,32.37,30.96,
30.15,29.65,26.92,26.72,24.95,22.13,20.88,16.06,16.02,15.13,14.00,13.81,
10.95。
5.45(s,2H),5.29(s,1H),5.10(d,J=10.1Hz,1H),5.01-4.96(m,1H),4.95-4.89(m,1H),
4.70-4.55(m,1H),4.06-3.98(m,2H),3.98-3.91(m,1H),3.66-3.58(m,1H),3.48-3.38(m,
1H),3.27(s,3H),3.15(s,3H),3.05(s,3H),2.86-2.68(m,2H),2.62-2.56(m,2H),2.44-
2.33(m,2H),2.26-2.17(m,1H),2.15-2.06(m,1H),2.05-1.97(m,2H),1.95-1.77(m,3H),
1.74(s,3H),1.63(s,3H),1.60-1.03(m,10H),0.98(d,J=6.5Hz,3H),0.89-0.84(m,5H),
0.82(d,J=6.4Hz,3H),0.78(d,J=6.7Hz,3H),0.73(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ210.95,208.02,199.37,169.72,167.51,167.21,146.94,142.69,139.84,138.36,
137.66,132.87,130.91,129.30,128.53,127.51,125.63,125.43,122.84,99.52,86.07,
82.77,80.41,78.24,76.25,74.21,67.02,66.74,57.45,57.28,55.96,51.30,51.16,
45.74,44.00,38.52,35.82,35.67,35.33,34.60,33.87,32.45,31.33,30.96,30.19,
29.67,26.92,26.75,24.96,22.41,22.15,20.87,16.62,16.05,15.18,14.37,13.92,
10.98。
7.6Hz,1H),7.16(d,J=7.6Hz,1H),6.46(s,1H),6.44-6.36(m,1H),6.26-6.18(m,1H),
6.17-6.08(m,2H),5.50-5.42(m,3H),5.29(s,1H),5.10(d,J=10.2Hz,1H),5.00-4.96(m,
1H),4.95-4.93(m,1H),4.69-4.62(m,1H),4.05-3.99(m,2H),3.98-3.94(m,1H),3.65-3.60(m,1H),3.48-3.40(m,1H),3.27(s,3H),3.16(s,3H),3.05(s,3H),2.84-2.69(m,2H),2.44-
2.38(m,2H),2.36(s,3H),2.27-2.17(m,1H),2.13-1.97(m,3H),1.96-1.88(m,2H),1.87-
1.78(m,2H),1.75(s,3H),1.63(s,3H),1.56-1.01(m,10H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.5Hz,3H),0.82(d,J=6.4Hz,3H),0.78(d,J=6.6Hz,3H),0.73(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ210.40,207.54,198.86,169.22,166.99,166.73,146.41,139.31,
138.06,137.85,137.15,132.34,130.43,128.81,128.56,126.99,125.68,124.81,122.69,
122.32,99.01,85.46,82.21,79.86,77.73,75.72,73.66,66.18,56.90,56.77,55.45,
50.78,50.64,45.23,43.50,37.99,35.28,35.17,34.80,33.33,32.07,31.87,30.45,
29.66,29.15,26.40,26.22,24.44,21.63,21.02,20.37,15.56,15.52,14.62,13.51,
13.30,10.45。
6.17-6.07(m,2H),5.51(s,2H),5.49-5.43(m,1H),5.29(s,1H),5.10(d,J=10.0Hz,1H),
5.01-4.96(m,1H),4.96-4.92(m,1H),4.68-4.61(m,1H),4.05-3.98(m,2H),3.97-3.93(m,
1H),3.64-3.62(m,1H),3.48-3.40(m,1H),3.32(s,3H),3.16(s,3H),3.05(s,3H),2.86-
2.70(m,2H),2.42-2.34(m,2H),2.27-2.17(m,1H),2.14-1.98(m,3H),1.97-1.89(m,2H),
1.89-1.79(m,2H),1.75(s,3H),1.63(s,3H),1.60-1.01(m,10H),0.98(d,J=6.5Hz,3H),
0.87(d,J=6.4Hz,3H),0.82(d,J=6.4Hz,3H),0.78(d,J=6.6Hz,3H),0.73(d,J=6.6Hz,
3H)。13C NMR(126MHz,DMSO)δ210.41,207.53,198.88,169.21,166.99,166.67,142.45,
139.31,137.86,137.16,132.34,130.28,130.23,129.49,129.39,128.96,127.58,126.99,
125.74,99.01,85.48,82.23,79.86,77.77,75.72,73.65,66.19,56.90,56.81,55.45,
50.76,50.61,45.23,43.50,37.99,35.31,35.17,34.80,33.34,31.89,30.44,29.65,
29.15,26.41,26.23,24.45,21.63,20.38,15.52,14.64,13.49,13.32,10.45。
6.17-6.07(m,2H),5.51(s,2H),5.49-5.43(m,1H),5.29(s,1H),5.10(d,J=10.0Hz,1H),
5.01-4.96(m,1H),4.96-4.92(m,1H),4.68-4.61(m,1H),4.05-3.98(m,2H),3.97-3.93(m,
1H),3.64-3.62(m,1H),3.48-3.40(m,1H),3.32(s,3H),3.16(s,3H),3.05(s,3H),2.86-
2.70(m,2H),2.42-2.34(m,2H),2.27-2.17(m,1H),2.14-1.98(m,3H),1.97-1.89(m,2H),
1.89-1.79(m,2H),1.75(s,3H),1.63(s,3H),1.60-1.01(m,10H),0.98(d,J=6.5Hz,3H),
0.87(d,J=6.4Hz,3H),0.82(d,J=6.4Hz,3H),0.78(d,J=6.6Hz,3H),0.73(d,J=6.6Hz,
3H)。13C NMR(126MHz,DMSO)δ210.41,207.53,198.88,169.21,166.99,166.67,142.45,
139.31,137.86,137.16,132.34,130.28,130.23,129.49,129.39,128.96,127.58,126.99,
125.74,99.01,85.48,82.23,79.86,77.77,75.72,73.65,66.19,56.90,56.81,55.45,
50.76,50.61,45.23,43.50,37.99,35.31,35.17,34.80,33.34,31.89,30.44,29.65,
29.15,26.41,26.23,24.45,21.63,20.38,15.52,14.64,13.49,13.32,10.45。
7.02(d,J=8.8Hz,2H),6.46(s,1H),6.45-6.34(m,1H),6.26-6.18(m,1H),6.17-6.06(m,
2H),5.44(s,2H),5.27(s,1H),5.10(d,J=10.1Hz,1H),5.00-4.91(m,2H),4.69-4.58(m,
1H),4.06-3.98(m,2H),3.99-3.92(m,1H),3.79(s,3H),3.68-3.57(m,1H),3.49-3.39(m,
1H),3.27(s,3H),3.16(s,3H),3.05(s,3H),2.88-2.67(m,2H),2.44-2.33(m,2H),2.27-
2.18(m,2H),2.14-2.07(m,1H),2.05-1.96(m,2H),1.96-1.78(m,3H),1.75(s,3H),1.63(s,
3H),1.55-1.03(m,10H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.4Hz,3H),0.82(d,J=6.4Hz,
3H),0.78(d,J=6.7Hz,3H),0.73(d,J=6.5Hz,3H)。13C NMR(126MHz,DMSO)δ210.39,
207.54,198.86,169.22,166.99,166.77,159.03,146.27,139.31,137.86,137.15,132.35,
130.42,127.01,126.49,123.11,121.78,114.33,99.01,85.46,82.22,79.86,77.71,
75.73,73.66,66.19,56.90,56.77,55.45,55.12,50.78,50.60,45.23,43.50,37.99,
35.28,35.17,34.80,33.32,31.87,29.66,29.56,29.22,29.15,26.42,26.22,24.44,
21.63,20.38,15.56,15.52,14.63,13.51,13.30,10.45。
6.17(m,1H),6.18-6.07(m,2H),5.46(dd,J=14.8,9.5Hz,1H),5.37(s,2H),5.28(s,1H),
5.14-5.05(m,1H),5.01-4.92(m,2H),4.62-4.56(m,1H),4.47(s,2H),4.06-3.96(m,2H),
3.98-3.87(m,1H),3.66-3.57(m,1H),3.49-3.39(m,1H),3.39-3.24(m,2H),3.18(s,3H),
3.16(s,3H),3.05(s,3H),2.85-2.69(m,2H),2.43-2.33(m,2H),2.28-2.17(m,1H),2.13-
2.06(m,1H),2.05-1.90(m,2H),1.90-1.78(m,3H),1.74(s,3H),1.63(s,3H),1.60-1.03(m,
10H),0.98(d,J=6.6Hz,3H),0.87(d,J=6.5Hz,3H),0.82(d,J=6.4Hz,3H),0.79(d,J=
6.7Hz,3H),0.73(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ210.45,207.53,198.88,
169.20,166.99,166.60,145.01,144.77,139.32,137.86,137.15,132.48,132.34,130.40,
130.05,126.98,124.88,124.20,116.53,115.97,110.87,99.00,85.50,82.23,79.86,
77.50,75.71,73.69,66.19,56.91,56.75,55.45,50.77,50.49,45.22,37.98,35.17,
34.80,33.32,32.04,31.87,30.48,29.66,29.56,29.09,26.41,26.22,24.43,21.64,
20.38,15.55,15.53,14.59,13.44,13.37,10.45。
1H),6.92(t,J=7.7Hz,1H),6.75(t,J=8.5Hz,1H),6.57-6.50(m,1H),6.46(s,1H),6.43-
6.33(m,1H),6.28-6.18(m,1H),6.18-6.08(m,2H),6.03-5.89(m,1H),5.54-5.42(m,1H),
5.35(s,2H),5.28(s,1H),5.02-4.96(m,1H),5.12-5.08(m,1H),4.95-4.89(m,1H),4.64-
4.51(m,1H),4.40(s,2H),4.05-3.97(m,2H),3.97-3.93(m,1H),3.65-3.59(m,1H),3.50-
3.39(m,1H),3.20(s,3H),3.16(s,3H),3.05(s,3H),2.86-2.70(m,2H),2.43-2.34(m,2H),
2.28-2.15(m,1H),2.14-2.06(m,1H),2.07-1.92(m,2H),1.91-1.80(m,3H),1.75(s,3H),
1.63(s,3H),1.60-1.02(m,10H),0.98(d,J=6.5Hz,3H),0.87(d,J=6.4Hz,3H),0.82(d,J=6.3Hz,3H),0.79(d,J=6.6Hz,3H),0.73(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ
210.41,207.54,198.87,169.22,166.99,166.68,151.90,150.01,145.75,139.32,137.86,
137.15,136.21,136.12,132.35,130.42,127.01,124.60,124.13,115.71,114.31,114.16,
112.27,99.01,85.47,82.22,79.81,77.52,75.72,73.66,66.18,56.90,56.75,55.45,
50.78,50.41,45.23,43.50,38.05,35.24,35.17,34.80,33.32,31.86,30.44,29.66,
29.57,29.09,28.98,26.41,26.22,24.45,21.63,20.37,15.56,15.52,14.60,13.49,
13.31,10.45。
1H),6.25-6.16(m,1H),6.16-6.09(m,2H),5.43(dd,J=14.7,9.6Hz,1H),5.35(s,2H),5.32(s,1H),5.15-5.05(m,1H),5.02–4.90(m,2H),4.63-4.42(m,2H),4.32-4.10(m,2H),4.05-
3.92(m,2H),3.75-3.57(m,2H),3.25(s,3H),3.16(s,3H),3.06(s,3H),2.91-2.67(m,2H),
2.45-2.32(m,4H),2.29-2.16(m,1H),2.13-2.04(m,2H),2.03-1.94(m,2H),1.91-1.81(m,
3H),1.76(s,3H),1.63(s,3H),1.57-1.06(m,10H),1.05-0.89(m,5H),0.85(d,J=6.5Hz,
3H),0.82(d,J=6.5Hz,3H),0.79(d,J=6.7Hz,3H),0.72(d,J=6.5Hz,3H)。13C NMR(101MHz,DMSO)δ210.92,208.86,199.40,169.73,168.49,167.51,167.21,139.72,138.35,
137.55,130.83,127.31,125.48,99.61,85.93,82.56,80.29,78.02,76.55,74.42,68.23,
66.53,57.49,57.38,56.69,56.08,55.88,51.17,50.64,47.00,46.52,45.73,44.05,
37.64,37.17,35.66,35.59,32.68,32.28,31.02,30.82,30.16,29.54,26.81,26.61,
25.00,22.96,22.66,22.02,21.39,16.06,15.00,14.00,13.68,12.28,10.84。
1H),6.27-6.18(m,1H),6.16-6.07(m,2H),5.46(dd,J=14.7,9.6Hz,1H),5.37(s,2H),5.33(s,1H),5.13-5.03(m,1H),5.01-4.91(m,2H),4.67-4.54(m,2H),4.30-4.13(m,2H),4.07-
3.94(m,3H),3.75-3.57(m,3H),3.26(s,3H),3.15(s,3H),3.05(s,3H),2.90-2.66(m,2H),
2.46-2.33(m,4H),2.28-2.15(m,1H),2.14-2.06(m,2H),2.04-1.93(m,2H),1.92-1.80(m,
3H),1.75(s,3H),1.62(s,3H),1.56-1.08(m,10H),1.07-0.89(m,5H),0.86(d,J=6.4Hz,
3H),0.81(d,J=6.4Hz,3H),0.78(d,J=6.7Hz,3H),0.73(d,J=6.7Hz,3H)。13C NMR(101MHz,DMSO)δ210.91,208.86,199.39,169.72,168.39,167.50,167.31,139.82,138.37,
137.66,130.93,127.51,125.57,99.51,85.95,82.72,80.37,78.08,76.22,74.12,68.98,
66.67,57.39,57.28,56.29,56.18,55.96,51.27,50.84,46.98,46.52,45.73,44.00,
37.74,37.27,35.67,35.58,32.58,32.38,31.12,30.92,30.06,29.44,26.91,26.71,
24.96,22.86,22.16,22.12,21.59,16.07,16.00,15.10,14.00,13.78,12.38,10.94。
5.12-5.06(m,1H),4.99-4.91(m,2H),4.70-4.57(m,1H),4.04-3.91(m,3H),3.64-3.57(m,
1H),3.46-3.40(m,1H),3.24(s,3H),3.15(s,3H),3.04(s,3H),2.85-2.66(m,2H),2.44-
2.31(m,2H),2.25-2.16(m,1H),2.12-2.05(m,2H),2.05-1.91(m,2H),1.90-1.77(m,5H),
1.74(s,3H),1.62(s,3H),1.57-1.01(m,10H),0.97(d,J=6.5Hz,3H),0.86(d,J=6.3Hz,
3H),0.81(d,J=6.3Hz,3H),0.77(d,J=6.4Hz,3H),0.72(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ210.38,207.52,198.85,169.20,168.98,166.97,162.72,160.78,145.35,
139.30,137.84,137.13,132.34,130.39,127.12,127.06,126.98,124.79,120.97,115.90,
115.73,98.99,85.44,82.20,80.10,77.48,75.71,73.65,68.46,66.17,57.69,56.88,
56.67,55.44,50.76,45.21,43.48,37.96,35.14,34.79,33.33,32.05,31.87,30.41,
29.55,28.98,26.38,26.20,24.43,21.61,20.35,17.05,15.54,15.50,14.63,13.28,
10.43。
2H),3.97-3.88(m,1H),3.66-3.56(m,1H),3.48-3.37(m,1H),3.24(s,3H),3.15(s,3H),
3.04(s,3H),2.85-2.65(m,2H),2.44-2.32(m,2H),2.30-2.16(m,1H),2.15-2.05(m,2H),
2.05-1.92(m,2H),1.93-1.77(m,6H),1.74(s,3H),1.62(s,3H),1.53-1.01(m,10H),0.97(d,J=6.4Hz,3H),0.86(d,J=6.4Hz,3H),0.81(d,J=6.3Hz,3H),0.77(d,J=6.4Hz,3H),
0.72(d,J=6.6Hz,3H)。13C NMR(126MHz,DMSO)δ210.91,208.03,199.37,169.73,169.47,
167.49,145.66,139.83,138.36,137.65,132.83,130.91,130.04,129.48,127.50,127.29,
125.34,121.96,99.52,85.99,82.74,80.63,78.03,76.24,74.18,66.70,58.26,57.41,
57.19,55.96,51.28,45.74,44.01,38.49,35.67,35.31,33.86,32.41,30.93,30.17,
29.51,26.91,26.74,24.96,22.14,20.88,17.56,17.44,16.06,16.03,15.17,14.00,
13.83,10.96。
1H),5.27(s,1H),5.14-5.04(m,1H),5.00-4.88(m,2H),4.64-4.55(m,1H),4.08-3.92(m,
3H),3.67-3.55(m,1H),3.49-3.38(m,1H),3.24(s,3H),3.15(s,3H),3.04(s,3H),2.85-
2.68(m,2H),2.44-2.34(m,1H),2.33(s,3H),2.26-2.15(m,1H),2.13-2.06(m,1H),2.06-
1.90(m,3H),1.82(d,J=6.8Hz,3H),1.74(s,3H),1.62(s,3H),1.58-1.02(m,10H),0.97(d,J=5.1Hz,3H),0.86(d,J=5.1Hz,3H),0.81(d,J=5.1Hz,3H),0.77(d,J=5.0Hz,3H),0.73(d,J=4.9Hz,3H)。13C NMR(126MHz,DMSO)δ210.95,208.01,199.36,169.72,169.51,
167.50,146.80,139.83,138.36,137.68,132.87,130.90,129.92,128.40,127.49,125.56,
125.43,121.12,99.51,86.06,82.77,80.65,78.01,76.25,74.23,66.74,58.19,58.14,
57.45,57.20,55.95,51.29,45.74,44.00,38.50,35.67,35.32,33.88,32.46,30.98,
30.19,29.52,26.98,26.91,26.75,24.95,22.15,21.30,20.87,17.57,17.46,16.06,
16.04,15.19,13.92,10.98。
5.42(m,1H),5.28(s,1H),5.10(d,J=10.7Hz,1H),4.99-4.96(m,1H),4.95-4.92(m,1H),
4.67-4.56(m,1H),4.06-3.97(m,2H),3.97-3.92(m,1H),3.66-3.59(m,1H),3.47-3.40(m,
1H),3.24(s,3H),3.15(s,3H),3.05(s,3H),2.84-2.68(m,2H),2.43-2.34(m,2H),2.25-
2.18(m,1H),2.14-2.07(m,2H),2.05-1.93(m,2H),1.89-1.79(m,5H),1.74(s,3H),1.62(s,
3H),1.60-1.02(m,10H),0.98(d,J=6.4Hz,3H),0.87(d,J=6.2Hz,3H),0.82(d,J=6.2Hz,
13
3H),0.78(d,J=6.3Hz,3H),0.73(d,J=6.6Hz,3H)。C NMR(126MHz,DMSO)δ210.39,
207.53,198.86,169.21,169.02,166.98,146.22,139.31,137.85,137.14,132.35,130.63,
130.41,128.88,127.88,126.99,125.08,124.81,121.07,99.00,85.46,82.22,80.11,
77.49,75.72,73.68,66.18,57.69,56.89,56.70,55.45,50.77,45.23,43.50,37.97,
35.16,34.80,33.35,31.88,30.44,29.66,29.00,26.40,26.22,24.44,21.62,20.37,
17.06,16.96,15.52,14.64,13.50,13.30,10.45。
3H),3.15(s,3H),3.04(s,3H),2.84-2.68(m,2H),2.62-2.56(m,2H),2.40-2.36(m,2H),
2.25-2.16(m,1H),2.14-2.06(m,1H),2.06-1.94(m,2H),1.85-1.78(m,6H),1.74(s,3H),
1.62(s,3H),1.60-1.00(m,15H),0.97(d,J=6.5Hz,3H),0.93-0.81(m,6H),0.81(d,J=
6.3Hz,3H),0.77(d,J=6.5Hz,3H),0.72(d,J=6.5Hz,3H)。13C NMR(126MHz,DMSO)δ210.37,
207.51,198.85,169.19,169.01,166.96,146.29,142.10,139.30,137.84,137.13,132.34,
130.39,128.74,128.09,126.97,125.04,124.80,120.64,98.99,85.45,82.21,80.10,
79.89,77.46,75.71,66.17,57.64,56.87,56.69,55.43,50.75,45.21,43.48,37.94,
35.15,34.81,33.33,31.87,30.82,30.47,29.65,29.55,28.98,26.38,26.20,24.43,
21.90,21.61,20.36,17.04,15.54,15.50,14.62,13.87,13.48,13.29,10.43。
2H),5.70-5.63(m,1H),5.46(dd,J=14.8,9.8Hz,1H),5.27(s,1H),5.09(d,J=10.1Hz,
1H),4.98-4.95(m,1H),4.95-4.92(m,1H),4.66-4.57(m,1H),4.03-3.98(m,2H),3.97-3.93(m,1H),3.65-3.58(m,1H),3.46-3.39(m,1H),3.24(s,3H),3.15(s,3H),3.04(s,3H),2.83-
2.69(m,2H),2.42-2.38(m,2H),2.36(s,3H),2.25-2.17(m,1H),2.14-2.06(m,2H),2.05-
1.95(m,3H),1.90-1.83(m,2H),1.82(d,J=7.3Hz,3H),1.74(s,3H),1.62(s,3H),1.58-
1.02(m,10H),0.97(d,J=6.5Hz,3H),0.86(d,J=6.4Hz,3H),0.81(d,J=6.3Hz,3H),0.77
13
(d,J=6.5Hz,3H),0.72(d,J=6.6Hz,3H)。C NMR(126MHz,DMSO)δ210.38,207.51,198.85,
169.20,169.01,166.96,146.29,139.30,138.00,137.84,137.13,132.33,130.53,130.39,
128.76,128.50,126.97,125.64,124.79,122.24,120.97,98.99,85.45,82.21,80.11,
77.47,75.70,73.66,66.17,57.66,56.87,56.69,55.44,50.75,45.21,43.48,37.95,
35.15,34.79,33.33,31.87,30.43,29.65,28.99,26.39,26.20,24.43,21.61,21.01,
20.35,17.04,16.93,15.54,15.50,14.62,13.49,13.29,10.43。
3.04(s,3H),2.83-2.67(m,2H),2.43-2.30(m,2H),2.28-2.15(m,2H),2.14-1.98(m,2H),
1.94-1.78(m,5H),1.74(s,3H),1.62(s,3H),1.56-1.03(m,9H),0.97(d,J=6.1Hz,3H),
0.86(d,J=5.9Hz,3H),0.81(d,J=6.0Hz,3H),0.77(d,J=5.7Hz,3H),0.72(d,J=6.1Hz,
3H)。13C NMR(101MHz,DMSO)δ210.95,208.03,199.38,169.71,169.38,167.48,142.97,
139.82,138.35,137.65,132.85,130.90,130.84,130.74,130.03,129.58,128.03,127.48,
125.36,124.69,99.50,82.73,80.62,78.07,76.21,74.17,66.69,58.25,57.41,57.27,
55.95,51.25,45.73,44.00,38.46,35.81,35.67,35.31,33.86,32.41,30.93,30.16,
29.51,26.90,26.72,24.95,22.13,20.86,17.46,17.38,16.04,16.02,15.15,13.96,
13.84,10.95。
2.14-2.06(m,1H),2.05-1.94(m,2H),1.93-1.84(m,2H),1.82(d,J=7.4Hz,3H),1.74(s,
3H),1.62(s,3H),1.57-1.02(m,10H),0.98(d,J=6.4Hz,3H),0.87(d,J=6.4Hz,3H),0.82(d,J=6.3Hz,3H),0.78(d,J=6.4Hz,3H),0.73(d,J=6.5Hz,3H)。13C NMR(126MHz,DMSO)δ
210.39,207.52,198.86,169.21,168.95,166.98,145.19,139.31,137.85,137.14,132.35,
131.87,130.41,129.88,127.07,126.99,124.81,121.48,120.86,99.00,85.46,82.22,
80.11,77.51,75.73,73.66,66.18,57.75,56.89,56.68,55.45,50.77,45.23,43.49,
37.98,35.16,34.80,33.34,31.88,30.42,29.67,28.99,26.40,26.22,24.44,21.63,
20.37,17.05,15.55,15.52,14.65,13.50,13.30,10.45。
6.45-6.34(m,1H),6.26-6.18(m,1H),6.17-6.06(m,2H),5.44(s,2H),5.27(s,1H),5.10(d,J=10.1Hz,1H),5.00-4.91(m,2H),4.69-4.58(m,1H),4.06-3.98(m,2H),3.99-3.92(m,
1H),3.79(s,3H),3.68-3.57(m,1H),3.49-3.39(m,1H),3.27(s,3H),3.16(s,3H),3.05(s,
3H),2.88-2.67(m,2H),2.44-2.33(m,2H),2.27-2.18(m,2H),2.14-2.07(m,1H),2.05-1.96(m,2H),1.96-1.78(m,3H),1.75(s,3H),1.63(s,3H),1.55-1.03(m,10H),0.98(d,J=
6.5Hz,3H),0.87(d,J=6.4Hz,3H),0.82(d,J=6.4Hz,3H),0.78(d,J=6.7Hz,3H),0.73(d,
13
J=6.5Hz,3H)。C NMR(126MHz,DMSO)δ210.39,207.54,198.86,169.22,166.99,166.77,
159.03,146.27,139.31,137.86,137.15,132.35,130.42,127.01,126.49,123.11,121.78,
114.33,99.01,85.46,82.22,79.86,77.71,75.73,73.66,66.19,56.90,56.77,55.45,
55.12,50.78,50.60,45.23,43.50,37.99,35.28,35.17,34.80,33.32,31.87,29.66,
29.56,29.22,29.15,26.42,26.22,24.44,21.63,20.38,15.56,15.52,14.63,13.51,
13.30,10.45。
5.62(m,1H),5.52(dd,J=14.2,9.6Hz,1H),5.35(s,1H),5.20-5.11(m,1H),5.07-4.95(m,
2H),4.64-4.54(m,1H),4.52(s,2H),4.12-3.96(m,3H),3.71–3.65(m,1H),3.54-3.44(m,
1H),3.21(s,3H),3.19(s,3H),3.11(s,3H),2.98-2.72(m,2H),2.51-2.39(m,2H),2.36-
2.24(m,1H),2.21-2.05(m,2H),2.03-1.86(m,3H),1.80(s,3H),1.68(s,3H),1.65-1.08(m,
10H),1.04(d,J=6.2Hz,3H),0.93(d,J=6.3Hz,3H),0.88(d,J=6.3Hz,3H),0.84(d,J=
5.5Hz,3H),0.79(d,J=6.2Hz,3H)。13C NMR(101MHz,DMSO)δ210.46,207.50,198.86,
169.18,168.79,166.97,144.79,139.32,137.83,137.14,132.44,132.33,130.38,129.99,
126.96,124.91,122.65,116.53,115.94,110.87,98.98,85.51,82.22,80.04,77.33,
75.69,73.72,66.18,57.43,56.91,56.69,55.42,50.74,45.20,43.47,38.05,37.83,
35.15,35.04,34.78,33.34,31.86,30.47,29.65,28.86,26.38,26.18,24.41,21.61,
20.36,20.34,16.88,15.52,14.59,13.39,10.44。
8.9Hz,1H),6.54(s,1H),6.50-6.41(m,1H),6.34-6.23(m,1H),6.23-6.11(m,2H),5.70-
5.61(m,1H),5.52(dd,J=14.7,9.6Hz,1H),5.36(s,1H),5.20-5.11(m,1H),5.07-4.93(m,
2H),4.66-4.53(m,1H),4.51(s,2H),4.13-3.98(m,3H),3.73-3.63(m,1H),3.56-3.46(m,
1H),3.22(s,3H),3.21(s,3H),3.11(s,3H),2.91-2.74(m,2H),2.49–2.40(m,2H),2.34-
2.21(m,1H),2.22-2.11(m,2H),2.11-1.97(m,2H),1.96-1.83(m,3H),1.80(s,3H),1.69(s,
3H),1.66-1.08(m,10H),1.04(d,J=6.5Hz,3H),0.93(d,J=6.5Hz,3H),0.88(d,J=6.4Hz,
3H),0.85(d,J=6.6Hz,3H),0.79(d,J=6.6Hz,3H)。13C NMR(101MHz,DMSO)δ227.19,
210.43,207.50,198.86,169.17,168.81,166.97,144.94,142.73,139.32,137.84,137.13,
132.33,130.38,128.10,127.63,126.97,122.62,119.19,118.41,112.51,98.99,85.51,
82.22,80.02,77.34,75.70,73.73,66.18,57.42,56.90,56.68,55.43,50.74,45.22,
43.47,38.22,37.91,35.15,34.79,33.35,31.93,30.48,29.65,28.91,26.39,26.22,
24.42,21.62,20.35,16.91,15.52,14.62,13.38,10.44。
2H),5.97-5.91(m,1H),5.63-5.55(m,1H),5.52-5.43(m,1H),5.28(s,1H),5.14-5.07(m,
1H),5.00-4.90(m,2H),4.59-4.50(m,1H),4.39(s,2H),4.08-3.93(m,3H).67-3.59(m,1H),
3.49-3.39(m,1H),3.17(s,3H),3.16(s,3H),3.05(s,3H),2.85-2.68(m,2H),2.45-2.31(m,
2H),2.27-2.16(m,1H),2.16-2.06(m,2H),2.06-1.92(m,3H),1.90-1.78(m,2H),1.74(s,
3H),1.62(s,3H),1.57-1.01(m,10H),0.98(d,J=5.5Hz,3H),0.87(d,J=5.8Hz,3H),0.82(d,J=4.9Hz,3H),0.78(d,J=4.0Hz,3H),0.73(d,J=5.7Hz,3H)。13C NMR(126MHz,DMSO)δ
210.42,207.53,198.85,191.52,169.20,168.88,166.97,152.23,151.88,149.98,147.76,
145.51,139.31,137.84,137.13,136.24,136.15,132.34,130.39,126.97,124.80,124.58,
122.53,122.47,115.75,115.69,114.26,114.12,112.25,112.23,99.73,98.99,85.46,
82.21,79.99,77.34,75.70,73.66,66.18,57.39,56.89,56.68,55.44,50.77,45.21,
43.49,42.12,38.12,37.89,35.15,34.79,33.32,31.84,30.41,29.64,29.55,28.95,