CN105503844A - C-13和c-7位结构改造的紫杉醇类化合物及其制备方法 - Google Patents

C-13和c-7位结构改造的紫杉醇类化合物及其制备方法 Download PDF

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CN105503844A
CN105503844A CN201510911938.3A CN201510911938A CN105503844A CN 105503844 A CN105503844 A CN 105503844A CN 201510911938 A CN201510911938 A CN 201510911938A CN 105503844 A CN105503844 A CN 105503844A
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林海霞
徐培佩
李青峰
崔永梅
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University of Shanghai for Science and Technology
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Abstract

本发明涉及一种C-13和C-7位结构改造的紫杉醇类化合物及其制备方法，该类似物的结构式为：其中<b>R1</b>为：正丙基羰基、正戊基羰基、2-噻吩羰基、5-溴正戊基羰基、4-甲苯基羰基、2-乙基正戊羰基等。<b>R2</b>为：2-呋喃羰基、2-噻吩羰基、4-氯甲基苯基羰基、4-正丙基苯基羰基等。本发明的巴卡亭III类似物在C-3ˊ-N和C-7位引入各种取代基，该类化合物设计的特点在于在C-3ˊ-N位各种杂环芳香内基团的同时也在C-7位引入不同取代基，进行对这类化合物的抗炎活性的研究，丰富了该类化合物，同时也为研究这类化合物的活性构效关系鉴定了非常有意义的基础。

Description

C-13和C-7位结构改造的紫杉醇类化合物及其制备方法
技术领域
本发明涉及一种紫杉醇类化合物及其合成方法。特别涉及一种C-13和C-7位结构改造的紫杉醇类化合物及其制备方法。
技术背景
紫杉醇(Paclitaxol，商品名Taxol)是从红豆杉属(Taxus）植物中分离提取的一种具有独特抗癌活性的新型抗癌药。其结构如下：
它的结构新颖、作用机制独特、活性强、作用广谱，紫杉醇一直被国际上公认为最好的抗肿瘤药物之一。近几年的研究进一步显示紫杉醇除抗癌作用外，可能还存在其它的抗炎治疗作用。在创伤、感染引起的全身炎症反应综合征(SIRS)和多器官功能障碍综合征(MODS)中，内毒素是重要的致病因子，而其化学本质为脂多糖(lipopolysaccharide，LPS)。越来越多的研究说明，MD-2在结合LPS及诱导其信号的胞内传导中都起着关键的作用。MD-2作为天然免疫识别过程的重要调控分子，有可能成为炎症性疾病治疗的“新靶点”。
针对靶向作用，提高生物利用度和活性，我们提出以MD-2为靶标对紫杉烷进行分子裁剪，以期合成对MD-2具有识别作用的高效低毒新型活性紫杉烷，从而达到抵御或减轻病原菌所导致的过度炎症损伤的目的。在此基础上，通过高通量筛选新型化合物生物活性，研究结构与活性的关系(SAR)，丰富药用样品资源库。
发明内容
本发明的目的之一在于提供一种C-13和C-7位结构改造的紫杉醇类化合物。
本发明的目的之二在于提供该紫杉醇类化合物的制备方法。
为达到上述目的，本发明采用如下反应合成过程：
其中：a-p中的R1为：正丁基羰基、正己基羰基、-噻吩羰基、-溴正戊基羰基、-甲苯基羰基、-乙基正戊羰基等。R2为：-呋喃羰基、-噻吩羰基、-氯甲基苯基羰基、-正丙基苯基羰基等。
根据上述反应合成过程，本发明采用如下技术方案：
一种C-13和C-7位结构改造的紫杉醇类化合物，其特征在于紫杉醇类化合物的结构式为：
；
其中R1为：正丁羰基、正己羰基、-噻吩羰基、-溴正戊基羰基、-甲苯基羰基、-乙基正己羰基；R2为：-呋喃羰基、-噻吩羰基、-氯甲基苯基羰基、-正丙基苯基羰基。
一种制备上述的C-13和C-7位结构改造的紫杉醇类化合物的方法，其特征在于该方法的具体步骤为：
a．将紫杉醇、三乙胺、酰氯和二甲氨基吡啶（DMAP）按1:3:1.2:1的摩尔比溶于甲苯中，在50~55oC下，搅拌反应至反应结束；用乙酸乙酯萃取，饱和食盐水洗涤，无水硫酸钠干燥，减压蒸除溶剂，初产物经分离提纯得白色固体7-酰基巴卡亭III，其结构为：；所述的酰氯的结构式为：、、、、、；
b.惰性气氛保护下，冰水浴下，将苯异丝氨酸和二氯亚砜按1:2.5的摩尔比溶于无水甲醇中，过夜反应；蒸出溶剂，乙酸乙酯和水萃取，取有机相干燥后旋干，经分离提纯，得甲酯化中间体；冰水浴下，将该甲酯化中间体和酰氯按1:3的摩尔比溶于四氢呋喃和饱和碳酸氢钠溶液混合溶液中，室温下搅拌反应至反应结束，蒸除四氢呋喃，经乙酸乙酯萃取、干燥后，蒸除溶剂，得粗产物；该粗产物经分离提纯得产物3-酰胺苯异丝氨酸甲酯，其结构式为：；所述的酰氯的结构式为：、、、；
c.在惰性气体保护下，将步骤b所得化合物3-酰胺苯异丝氨酸甲酯和4-甲氧基苯甲醛二甲基缩醛按1：1.5的摩尔比溶于重蒸的甲苯中，加入催化量的对甲苯磺酸吡啶盐，110oC下搅拌两个小时，乙酸乙酯萃取，无水硫酸钠干燥，减压蒸除溶剂；粗产物经分离提纯得黄色油状液体(4S,5R)-3-酰基-2-(4-甲氧基苯基)-4-苯基-5-恶唑啉羧酸甲酯，其结构式为：；
d.将步骤c所得化合物(4S,5R)-3-酰基-2-(4-甲氧基苯基)-4-苯基-5-恶唑啉羧酸甲酯溶于无水甲醇中，加入NaOH溶液水解，其中(4S,5R)-3-酰基-2-(4-甲氧基苯基)-4-苯基-5-恶唑啉羧酸甲酯与NaOH的摩尔比为1：1.2室温下搅拌2h；反应结束后，减压蒸除溶剂，无水乙醚萃取；调节水相pH为2，出现饱和羧酸白色固体，水相用乙酸乙酯萃取3次，合并有机相，有机相用饱和食盐水洗3次，无水Na2SO4干燥；除去溶剂得中间产物，将该中间产物、二环己基碳二亚胺（DCC）和二甲氨基吡啶（DMAP）按1:2:3:1的摩尔比溶于甲苯中，40℃反应至反应结束；用乙酸乙酯萃取，再用饱和NaCl溶液洗涤，有机相用Na2SO4干燥，除去溶剂，初产物经分离提纯,得白色固体产物7-取代-13-(4S,5R)-3ˊ-酰基-2ˊ-(4-甲氧基苯基)-4ˊ-苯基-5ˊ-恶唑啉紫杉醇，其结构式为：
；
e.将化合物7-取代-13-(4S,5R)-3ˊ-酰基-2ˊ-(4-甲氧基苯基)-4ˊ-苯基-5ˊ-恶唑啉紫杉醇和对苯甲磺酸按1:0.5的摩尔比溶于无水甲醇中，室温下反应至反应结束，混合液用乙酸乙酯稀释，分别用饱和碳酸氢钠和饱和食盐水洗涤，无水Na2SO4干燥，除去溶剂，粗产物经分离提纯得白色固体C-13和C-7位结构改造的紫杉醇类化合物。
本发明的巴卡亭III类似物在C-3ˊ-N和C-7位引入各种取代基，该类化合物设计的特点在于在C-3ˊ-N位各种杂环芳香内基团的同时也在C-7位引入不同取代基，进行对这类化合物的抗炎活性的研究，丰富了该类化合物，同时也为研究这类化合物的活性构效关系鉴定了非常有意义的基础。
附图说明
图1合成化合物与紫杉醇对在鼠RAW264.7细胞中由LPS刺激的肿瘤坏死因子（TNFa）的抑制作用图。
具体实施方式
实施例1：制备化合物3’-N-苯并呋喃酰-7-正丁酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
A．化合物1(100mg,1mmol)，三乙胺(52mg,3mmol)，酰氯(1.2mmol)和DMAP(55mg,1mmol)加入6mL的甲苯中,油浴加热50oC反应,TLC检测至反应结束。用10mL乙酸乙酯萃取三次，再用饱和NaCl溶液洗涤三次，有机相用Na2SO4干燥，减压蒸馏除去溶剂，初产物经柱层析分离（薄层层析硅胶),得白色固体产物2a(80-90%)。2a:1HNMR(500MHz,CDCl3)δ(ppm):0.83(t,J=13.3Hz,3H),1.11(s,3H),1.13(s,3H),1.27-1.33(m,4H),1.80(s,3H),1.87(br,1H),2.10(s,3H),2.13(s,3H),2.18-2.37(m,3H),2.26(s,3H),2.54-2.63(m,1H),3.95(d,J=8.3Hz,1H),4.13(d,J=8.3Hz,1H),4.29(d,J=9.5Hz,1H),4.83(t,J=17.6Hz,1H),5.00(d,J=9.4Hz,1H),5.58-5.61(m,2H),6.28(s,1H),7.45(t,J=15.4Hz,2H),7.56(t,J=15.4Hz,1H),8.06(d,J=7.5Hz,1H);13CNMR(125MHz,CDCl3)δ(ppm):1.02,10.75,13.60,15.19,18.03,20.06,20.80,22.58,26.64,29.69,33.44,36.08,38.43,42.80,47.39,56.26,67.93,71.26,74.40,75.84,76.37,77.22,78.63,80.69,84.03,128.64,129.30,130.10,131.68,133.09,144.58,167.02,168.85,170.66,172.82,202.46;
B．将原料苯异丝氨酸（3）（100mg,0.5mmol）溶于3ml的无水甲醇中，N2保护，0oC下加入SOCl2（92mg,0.76mmol）0.05ml，过夜反应。用饱和碳酸氢钠淬灭反应，去除溶剂，水相用乙酸乙酯萃取三次，合并有机相，有机相用饱和食盐水洗3次，无水Na2SO4干燥，减压蒸除溶剂得甲酯化中间体117mg；将甲酯化中间体化合物溶于THF(10mL)和饱和碳酸氢钠溶液（10mL）混合溶液中，0oC下加入2-呋喃酰氯（192mg，0.15mmol）1.5eq，室温下搅拌3h。TLC跟踪至反应结束，减压蒸除THF，水相用乙酸乙酯萃取3次，合并有机相，有机相用饱和食盐水洗3次用无水Na2SO4干燥，减压蒸除溶剂；粗产物经柱层析纯化（石油醚:乙酸乙酯=3:1）的白色固体产物160mg（4a），产率为85%；
4a:1HNMR(500MHz,CDCl3)δ(ppm):3.87(s,3H),4.67(d,J=2.0Hz,1H),5.79(d,J=9.5Hz,1H),7.29-7.35(m,2H),7.38-7.46(m,3H),7.49-7.54(m,4H),7.67(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):30.33,53.33,54.36,73.19,111.15,111.94,122.74,123.77,127.01,128.08,128.80,138.49,148.09,158.28,173.19;
C.将化合物4a溶于20mL重蒸的甲苯中，加入催化量的对甲苯磺酸吡啶盐（9.5mg，0.03mmol）0.1eq，和4-甲氧基丙烯（0.1mL，0.08mmol）3.0eq，N2保护，100oC下搅拌两个小时。用饱和碳酸氢钠淬灭反应，乙酸乙酯萃取3次，合并有机相，有机相用饱和食盐水洗3次，无水Na2SO4干燥，减压蒸除溶剂；粗产物经柱层析纯化（石油醚:乙酸乙酯=5:1）得淡黄色油状液体123mg（5a），产率为81%。
:1HNMR(500MHz,CDCl3)δ(ppm):3.80(s,3H),3.85(s,3H),5.01(s,1H),5.95(br,1H),6.90(d,J=8.5Hz,2H),7.13(br,1H),7.20-7.24(m,2H),7.30-7.39(m,4H),7.45(d,J=7.4Hz,2H),7.55(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):14.22,21.03,52.84,55.25,60.37,64.35,91.78,111.88,113.34,113.56,122.62,123.72,126.69,127.12,128.06,128.64,129.03,147.85,154.87,160.06,170.36;
D.将化合物5a用于8mL的无水甲醇中，加入4mLNaOH溶液，室温下搅拌2h。反应结束后，减压蒸除溶剂，用2mL无水乙醚萃取，取下层水相，加入3N盐酸调节PH=2（出现大量白色固体），用乙酸乙酯萃取3次，合并有机相，有机相用饱和食盐水洗3次，无水Na2SO4干燥。将压蒸除得产物。将所得产物，化合物2a（75.19mg，0.13mmol），DCC(54.37mg，0.26mmol)，DMAP（16.1mg，0.13mmol）溶于5mL的甲苯中，90oC下搅拌两个小时。TLC跟踪反应结束，过滤除去不溶固体，有机相用乙酸乙酯稀释，饱和食盐水洗3次，用无水Na2SO4干燥，减压蒸除溶剂；粗产物经柱层析纯化（石油醚:乙酸乙酯=1:1）的白色固体100mg（6a）产率为80%。
:1HNMR(500MHz,CDCl3)δ(ppm):0.91(t,J=15.3Hz,3H),1.16(s,3H),1.22(s,3H),1.56-1.54(m,3H),1.79(s,3H),1.95(s,1H),2.01(s,3H),2.10(s,3H),2.14(s,3H),2.18-2.37(m,5H),2.56-2.53(m,1H),3.80(s,3H),3.97(d,J=7.3Hz,1H),4.26(d,J=8.5Hz,1H),4.90(d,J=9.5Hz,1H),4.97(d,J=3.6Hz,1H),5.59-5.67(m,2H),5.99(br,1H),6.29(s,1H),6.31(d,J=10.3Hz,1H),6.89(d,J=9.6Hz,2H),7.20(t,J=5.3Hz,2H),7.27-7.32(m,3H),7.34-7.37(m,3H),7.45(t,J=15.6Hz,4H),7.54(d,J=7.6Hz,2H),7.59(t,J=5.5Hz,1H),8.04(d,J=8.3Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.86,13.62,14.96,18.00,20.71,21.03,21.83,26.39,33.90,35.63,36.03,46.91,55.29,56.10,60.39,64.63,71.04,71.81,74.54,75.12,76.32,78.85,80.63,84.01,91.86,111.94,113.66,113.77,122.59,123.72,126.61,127.20,128.24,128.74,128.83,129.16,130.06,133.76,140.31,147.69,154.86,160.11,166.11,166.87,168.73,171.16,173.69,202.02;
E.将化合物6a溶于4mL的甲酸中，室温下反应4h，混合液用饱和碳酸氢钠溶液猝灭，TLC跟踪反应结束，混合液用乙酸乙酯稀释，饱和碳酸氢钠和饱和食盐水分别洗3次，无水Na2SO4干燥，减压蒸除溶剂，粗产物经薄层层析分离得白色固体30mg（7a），产率为40%。
:1HNMR(500MHz,CDCl3)δ(ppm):0.94(t,J=15.3Hz,3H),1.08-1.15(m,1H),1.18(s,3H),1.20(s,3H),1.27(s,2H),1.31-1.37(m,1H),1.58-1.71(m,3H),1.84(s,3H),1.90(s,3H),1.97(s,1H),2.16(s,3H),2.20-2.30(m,1H),2.32-2.37(m,3H),2.40(s,3H),2.57-2.65(m,1H),3.94(d,J=6.4Hz,1H),3.98(br,1H),4.21(d,J=8.5Hz,1H),4.33(d,J=9.4Hz,1H),4.83(s,1H),4.96(d,J=10.6Hz,1H),5.58(q,J=7.7Hz,1H),5.69(d,J=7.4Hz,1H),5.83(d,J=10.3Hz,1H),6.21(t,J=8.3Hz,1H),6.26(s,1H),7.29(t,J=13.3Hz,2H),7.36(t,J=15.3Hz,1H),7.41-7.46(m,4H),7.51-7.58(m,5H),7.60-7.66(m,3H),8.14(d,J=7.3Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):1.02,10.83,13.60,14.19,14.75,18.02,20.72,22.56,24.91,25.58,26.57,29.69,33.48,33.86,35.54,36.03,43.22,47.02,54.43,56.24,71.09,72.08,73.41,74.33,75.27,76.46,77.25,78.45,81.16,83.93,111.34,112.01,122.74,123.80,127.18,127.45,128.34,128.74,128.96,129.14,130.19,133.04,133.79,137.87,140.30,147.90,154.86,158.46,166.85,168.85,168.79,170.41,172.01,172.82,201.95;
HR-MS:calcdforC53H57NO16([M+H]+),964.3755;found,964.3741;
实施例二：制备化合物3’-N-苯并呋喃酰-7-正己酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
方法同实施示例一：
2b:1HNMR(500MHz,CDCl3)δ(ppm):0.87(t,J=14.3Hz,3H),1.06(s,3H),1.12(s,3H),1.27-1.33(m,3H),1.52-1.60(m,2H),1.79(s,3H),1.87(br,1H),2.09(s,3H),2.15(s,3H),2.18-2.37(m,3H),2.28(s,3H),2.55-2.62(m,1H),3.99(d,J=8.5Hz,1H),4.14(d,J=8.4Hz,1H),4.30(d,J=9.3Hz,1H),4.83(t,J=17.6Hz,1H),4.97(d,J=9.6Hz,1H),5.58-5.61(m,2H),6.28(s,1H),7.47(t,J=15.5Hz,2H),7.60(t,J=15.6Hz,1H),8.09(d,J=7.7Hz,1H);13CNMR(125MHz,CDCl3)δ(ppm):10.73,13.89,14.16,15.18,20.12,20.77,21.02,22.25,22.51,24.14,26.57,31.15,34.11,38.58,42.75,47.39,56.15,60.42,71.33,74.44,75.84,76.32,76.81,166.90,168.90,170.64,173.12,202.52;
4b:1HNMR(500MHz,CDCl3)δ(ppm):3.87(s,3H),4.67(d,J=2.0Hz,1H),5.79(d,J=9.5Hz,1H),7.29-7.35(m,2H),7.38-7.46(m,3H),7.49-7.54(m,4H),7.67(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):30.33,53.33,54.36,73.19,111.15,111.94,122.74,123.77,127.01,128.08,128.80,138.49,148.09,158.28,173.19;
5b:1HNMR(500MHz,CDCl3)δ(ppm):3.80(s,3H),3.85(s,3H),5.01(s,1H),5.95(br,1H),6.90(d,J=8.5Hz,2H),7.13(br,1H),7.20-7.24(m,2H),7.30-7.39(m,4H),7.45(d,J=7.4Hz,2H),7.55(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):14.22,21.03,52.84,55.25,60.37,64.35,91.78,111.88,113.34,113.56,122.62,123.72,126.69,127.12,128.06,128.64,129.03,147.85,154.87,160.06,170.36;
6b:1HNMR(500MHz,CDCl3)δ(ppm):0.91(t,J=15.5Hz,3H),1.19(s,3H),1.25(s,3H),1.29-1.35(m,4H),1.57-1.64(m,2H),1.82(s,3H),1.91(s,1H),2.03(s,3H),2.13(s,3H),2.17(s,3H),2.22-2.41(m,5H),2.59-2.66(m,1H),3.84(s,3H),4.00(d,J=6.6Hz,1H),4.16(d,J=9.4Hz,1H),4.30(d,J=8.8Hz,1H),4.94(d,J=9.6Hz,1H),5.00(d,J=4.6Hz,1H),5.64(q,J=18.2Hz,1H),5.69(d,J=7.3Hz,1H),6.02(br,1H),6.32(s,2H),6.92(d,J=9.2Hz,2H),7.23(t,J=15.5Hz,2H),7.29-7.40(m,6H),7.48(t,J=15.4Hz,4H),7.57(d,J=8.5Hz,2H),7.62(t,J=15.5Hz,1H),8.07(d,J=8.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.86,13.93,14.20,14.97,20.71,21.05,21.84,22.30,24.15,26.41,31.19,33.36,34.07,35.62,43.29,46.92,55.31,56.09,60.40,64.63,71.04,71.80,74.55,75.11,76.33,78.90,80.64,84.03,91.88,111.95,113.68,113.78,122.60,123.72,126.62,127.20,128.24,128.65,128.75,128.84,129.14,130.07,133.05,140.34,147.70,154.87,160.12,166.91,168.72,169.81,172.90,202.02;
7b:1HNMR(500MHz,CDCl3)δ(ppm):0.90(t,J=15.5Hz,3H),1.18(s,3H),1.20(s,3H),1.59(br,2H),1.82(s,3H),1.89(s,3H),1.95(s,1H),2.15(s,3H),2.21-2.36(m,4H),2.39(s,3H),2.60(br,1H),3.94(s,2H),4.20(d,J=9.3Hz,1H),4.32(d,J=7.7Hz,1H),4.82(s,1H),4.95(d,J=9.3Hz,1H),5.57(t,J=16.6Hz,1H),5.68(d,J=6.6Hz,1H),5.83(d,J=10.2Hz,1H),6.20(t,J=7.7Hz,1H),6.25(s,1H),7.36(d,J=8.2Hz,1H),7.42(m,4H),7.50-7.56(m,5H),7.58-7.56(m,3H),7.58-7.65(m,3h),8.13(d,J=7.3Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):1.03,10.83,13.92,14.92,20.72,22.29,22.56,24.16,26.57,29.69,31.18,33.46,34.09,35.55,43.22,47.01,54.44,56.22,71.09,72.09,73.38,74.34,75.25,76.46,78.44,81.16,83.94,111.36,112.01,123.80,127.15,127.25,127.45,128.35,128.72,128.96,129.15,130.18,133.05,133.78,137.85,140.87,154.86,158.49,166.84,168.79,170.41,172.04,173.03;
HR-MS:calcdforC55H61NO16([M+H]+),992.4068;found,992.4075;
实施例三：制备化合物3’-N-苯并呋喃酰-7-噻吩酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
方法同示例一：
2c:1HNMR(500MHz,CDCl3)δ(ppm):1.07(s,3H),1.15(s,3H),1.83(br,1H),1.91(s,3H),1.94-1.98(m,1H),2.01(s,3H),2.14(s,3H),2.31(s,3H),2.28-2.34(m,2H),2.60(br,1H),2.74-2.81(m,1H),4.07(d,J=7.3Hz,1H),4.20(d,J=8.2Hz,1H),4.35(d,J=8.4Hz,1H),4.86(t,J=16.5Hz,1H),5.01(d,J=9.4Hz,1H),5.68(d,J=7.4Hz,1H),5.74(q,J=17.4Hz,1H),6.44(s,1H),7.07(q,J=9.4Hz,1H),7.49(t,J=16.8Hz,2H),7.54(dd,J=4.2Hz,J=1.3Hz,1H),7.61(t,J=14.3Hz,1H),7.74(dd,J=4.6Hz,J=1.4Hz,1H),8.12(d,J=7.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.86,14.19,15.21,20.17,20.59,22.54,26.59,33.44,38.59,42.85,47.20,53.46,56.34,60.43,67.73,72.54,74.48,75.51,76.36,78.69,80.52,83.96,127.53,128.66,129.33,130.10,131.66,132.58,133.60,133.71,145.01,160.95,166.98,168.52,170.72,202.58;
4c:1HNMR(500MHz,CDCl3)δ(ppm):3.87(s,3H),4.67(d,J=2.0Hz,1H),5.79(d,J=9.5Hz,1H),7.29-7.35(m,2H),7.38-7.46(m,3H),7.49-7.54(m,4H),7.67(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):30.33,53.33,54.36,73.19,111.15,111.94,122.74,123.77,127.01,128.08,128.80,138.49,148.09,158.28,173.19;
5c:1HNMR(500MHz,CDCl3)δ(ppm):3.80(s,3H),3.85(s,3H),5.01(s,1H),5.95(br,1H),6.90(d,J=8.5Hz,2H),7.13(br,1H),7.20-7.24(m,2H),7.30-7.39(m,4H),7.45(d,J=7.4Hz,2H),7.55(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):14.22,21.03,52.84,55.25,60.37,64.35,91.78,111.88,113.34,113.56,122.62,123.72,126.69,127.12,128.06,128.64,129.03,147.85,154.87,160.06,170.36;
6c:1HNMR(500MHz,CDCl3)δ(ppm):1.20(s,3H),1.25(s,3H),1.04-1.37(m,2H),1.51-1.57(m,1H),1.93(s,3H),1.99(s,1H),2.02(s,3H),2.06(s,3H),2.17(s,3H),2.27-2.38(m,3H),2.76-2.83(m,1H),3.84(s,3H),4.07(d,J=7.3Hz,1H),4.20(d,J=8.5Hz,1H),4.97(d,J=9.2Hz,1H),5.02(d,J=3.3Hz,1H),5.72-5.79(m,2H),6.03(br,1H),6.34(t,J=18.2Hz,1H),6.47(s,1H),6.94(d,J=8.1Hz,2H),7.09(t,J=8.6Hz,1H),7.23(t,J=15.6Hz,2H),7.33-7.40(m,6H),7.49(t,J=16.3Hz,4H),7.56(t,J=12.2Hz,3H),7.62(t,J=14.3Hz,1H),7.77(d,J=4.4Hz,1H),8.08(d,J=7.7Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.98,14.20,15.00,20.50,21.04,21.11,21.85,26.38,33.39,33.91,35.70,43.28,46.71,55.31,56.24,60.40,64.63,71.81,72.25,74.60,74.77,76.34,78.93,80.58,83.97,91.89,111.95,113.70,113.80,122.61,123.74,126.62,127.22,127.54,128.25,128.68,128.75,128.86,129.16,130.08,132.60,133.28,133.60,133.73,133.80,140.41,147.69,154.88,160.13,160.79,166.91,168.33,169.97,171.18,202.08;
7c：1HNMR(500MHz,CDCl3)δ(ppm):1.21(s,6H),1.83-1.92(m,2H),1.94(s,6H),2.01(s,3H),1.97-2.04(m,2H),2.37(d,J=9.3Hz,2H),2.42(s,3H),2.74-2.82(m,1H),3.90(br,1H),4.02(d,J=7.7Hz,1H),4.26(d,J=8.2Hz,1H),4.36(d,J=8.3Hz,1H),4.85(s,1H),5.00(d,J=10.5Hz,1H),5.68-5.76(m,2H),5.84(d,J=8.5Hz,1H),6.22(t,J=18.4Hz,1H),6.41(s,1H),7.09(t,J=18.5Hz,1H),7.30(d,J=8.6Hz,1H),7.38(d,J=8.6Hz,1H),7.41-7.47(m,4H),7.53-7.58(m,6H),7.64(t,J=15.6Hz,2H),7.76(d,J=4.6Hz,1H),8.16(d,J=8.6Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.96,14.19,14.71,20.51,20.87,22.57,26.53,29.70,33.49,35.62,43.22,46.78,54.44,56.35,60.42,72.18,72.27,73.33,74.42,74.89,76.47,77.24,78.55,81.06,83.90,111.39,112.01,122.75,123.82,127.13,127.29,127.44,127.55,128.39,128.76,129.01,129.16,130.22,132.66,133.26,133.52,133.82,140.37,147.84,154.86,158.51,160.86,166.89,168.39,170.43,172.16,202.00;HR-MS:calcdforC54H53NO16S([M+H]+),1004.3163;found,1004.3152;
实施例四：制备化合物3’-N-苯并呋喃酰-7-2-乙基己酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
方法同示例一：
2d:1HNMR(500MHz,CDCl3)δ(ppm):0.78-0.94(m,8H),1.04(s,3H),1.14(s,3H),1.18-1.31(m,3H),1.36-1.65(m,5H),2.13(s,3H),2.16(s,3H),2.28(s,3H),2.22-2.31(m,2H),2.56-2.64(m,1H),4.00(d,J=6.6Hz,1H),4.16(d,J=7.6Hz,1H),4.31(d,J=8.6Hz,1H),4.82(t,J=17.6Hz,1H),4.31(d,J=9.6Hz,1H),5.56(t,J=18.6Hz,1H),5.64(d,J=6.6Hz,1H),6.41(s,1H),7.47(t,J=15.5Hz,2H),7.60(t,J=15.4Hz,1H),8.10(d,J=9.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.81,11.08,11.36,13.90,14.16,15.02,20.11,20.78,22.51,22.60,23.67,23.92,26.52,28.85,28.99,29.70,30.32,33.41,38.51,42.68,45.98,46.03,47.29,56.55,60.44,67.65,71.19,71.22,74.49,75.89,76.37,78.61,80.49,83.85,128.62,129.35,130.08,131.56,133.65,145.10,166.93,168.81,170.70,175.02,202.52;
4d:1HNMR(500MHz,CDCl3)δ(ppm):3.87(s,3H),4.67(d,J=2.0Hz,1H),5.79(d,J=9.5Hz,1H),7.29-7.35(m,2H),7.38-7.46(m,3H),7.49-7.54(m,4H),7.67(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):30.33,53.33,54.36,73.19,111.15,111.94,122.74,123.77,127.01,128.08,128.80,138.49,148.09,158.28,173.19;
5d:1HNMR(500MHz,CDCl3)δ(ppm):3.80(s,3H),3.85(s,3H),5.01(s,1H),5.95(br,1H),6.90(d,J=8.5Hz,2H),7.13(br,1H),7.20-7.24(m,2H),7.30-7.39(m,4H),7.45(d,J=7.4Hz,2H),7.55(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):14.22,21.03,52.84,55.25,60.37,64.35,91.78,111.88,113.34,113.56,122.62,123.72,126.69,127.12,128.06,128.64,129.03,147.85,154.87,160.06,170.36;
6d:1HNMR(500MHz,CDCl3)δ(ppm):0.81-0.93(m,7H),1.20(s,3H),1.21(s,3H),1.24(t,J=14.3Hz,3H),1.41-1.68(m,5H),1.83(s,3H),2.02(s,3H),2.05(s,3H),2.14(s,3H),2.20(s,3H),2.25-2.36(m,3H),2.60-2.67(m,1H),3.81(s,3H),4.01(d,J=6.5Hz,1H),4.16(d,J=7.3Hz,1H),4.29(d,J=8.5Hz,1H),4.92(d,J=1.2Hz,1H),5.60(d,J=8.7Hz,1H),6.03(s,1H),6.32(t,J=17.2Hz,2H),6.46(s,1H),6.91((d,J=7.3Hz,1H),7.21(t,J=15.2Hz,2H),7.30-7.39(m,6H),7.44-7.51(m,4H),7.53-7.61(m,5H),8.05(d,J=9.6Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.91,11.11,11.42,13.95,14.19,14.85,20.68,21.01,21.05,21.84,22.65,23.62,23.93,26.32,28.86,29.01,29.64,30.32,33.40,35.69,43.22,45.85,45.94,46.67,55.28,56.41,56.45,60.38,64.61,70.93,71.80,74.63,75.04,76.36,78.82,80.55,83.88,91.87,111.92,113.66,113.76,122.56,123.71,126.61,127.19,128.22,128.63,128.73,128.87,129.31,133.73,140.39,147.69,154.85,160.11,166.81,168.52,169.89,170.00,171.16,174.73,202.05;
7d:1HNMR(500MHz,CDCl3)δ(ppm):0.79-0.93(m,3H),1.15(s,3H),1.18(s,3H),1.26-1.65(m,9H),1.82(s,3H),1.82(s,3H),1.92(s,3H),2.16(s,3H),2.24-2.33(m,3H),2.35(s,3H),2.56-2.64(m,1H),3.93(d,J=8.3Hz,1H),4.07(br,1H),4.21(d,J=9.2Hz,1H),4.32(d,J=7.6Hz,1H),4.82(s,1H),4.93(d,J=9.1Hz,1H),5.51(t,J=16.3Hz,1H),5.70(d,J=6.5Hz,1H),5.78(d,J=10.6Hz,1H),6.17(t,J=7.5Hz,1H),6.38(s,1H),7.36(d,J=8.8Hz,1H),7.42(m,4H),7.50-7.56(m,5H),7.58-7.56(m,3H),7.58-7.65(m,3H),8.13(d,J=7.3Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.81,11.18,11.38,14.03,14.43,20.62,20.63,20.73,22.34,22.43,23.69,23.83,25.45,27.84,27.99,28.61,29.69,31.22,33.47,35.70,43.24,45.76,45.95,46.73,54.83,56.51,56.54,71.87,72.27,75.42,77.43,81.98,83.80,112.39,113.01,123.75,123.82,126.13,127.29,127.44,127.65,129.39,129.76,130.01,130.16,131.22,132.66,133.26,133.52,134.82,140.37,146.84,156.86,158.51,164.86,166.89,167.39,170.43,173.16,202.50;
HR-MS:calcdforC57H65NO16([M+H]+),1020.4381;found,1020.4374;
实施例五：制备化合物3’-N-2-苯并呋喃基-7-溴代己酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
方法同示例一：
2e:1HNMR(500MHz,CDCl3)δ(ppm):1.07(s,3H),1.12(s,3H),1.40-1.52(m,3H),1.56-1.68(m,3H),1.72(s,3H),1.82-1.90(m,3H),2.09(s,3H),2.16(s,3H),2.20-2.27(m,1H),2.28(s,3H),2.32-2.41(m,2H),3.40(t,J=13.4Hz,2H),3.99(d,J=6Hz,1H),4.15(d,J=9.2Hz,1H),4.31(d,J=8.5Hz,1H),4.82(t,J=16.5Hz,1H),4.97(d,J=9.2Hz,1H),5.61(m,2H),6.27(s,1H),7.48(t,J=15.3Hz,2H),7.61(t,J=15.5Hz,1H),8.10(d,J=9.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.75,14.18,15.21,20.11,20.83,22.54,23.43,23.84,26.61,27.45,27.57,32.35,33.37,33.45,33.61,33.77,38.53,42.75,47.40,56.15,60.46,67.72,71.49,74.41,75.83,76.33,78.60,80.59,83.97,128.64,129.30,130.08,131.44,133.69,144.91,166.94,169.01,170.73,172.72,202.48.
4e:1HNMR(500MHz,CDCl3)δ(ppm):3.87(s,3H),4.67(d,J=2.0Hz,1H),5.79(d,J=9.5Hz,1H),7.29-7.35(m,2H),7.38-7.46(m,3H),7.49-7.54(m,4H),7.67(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):30.33,53.33,54.36,73.19,111.15,111.94,122.74,123.77,127.01,128.08,128.80,138.49,148.09,158.28,173.19;
5e:1HNMR(500MHz,CDCl3)δ(ppm):3.80(s,3H),3.85(s,3H),5.01(s,1H),5.95(br,1H),6.90(d,J=8.5Hz,2H),7.13(br,1H),7.20-7.24(m,2H),7.30-7.39(m,4H),7.45(d,J=7.4Hz,2H),7.55(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):14.22,21.03,52.84,55.25,60.37,64.35,91.78,111.88,113.34,113.56,122.62,123.72,126.69,127.12,128.06,128.64,129.03,147.85,154.87,160.06,170.36;
6e:1HNMR(500MHz,CDCl3)δ(ppm):1.18(s,3H),1.24(s,3H),1.43-1.50(m,2H),1.60-1.68(m,3H),1.81(s,3H),1.85-1.92(m,3H),2.04(s,1H),2.11(s,3H),2.23-2.44(m,5H),2.17(s,3H),2.58-2.66(m,1H),3.42(t,J=14.1Hz,1H),3.82(s,3H),3.99(d,J=7.3Hz,1H),4.15(d,J=9.5Hz,1H),4.29(d,J=8.7Hz,1H),4.93(d,J=10.3Hz,1H),5.01(s,1H),5.64(t,J=17.3Hz,1H),5.68(d,J=7.5Hz,1H),6.02(br,1H),6.30(s,1H),6.33(t,J=18.2Hz,1H),6.92(d,J=8.4Hz,1H),7.22(t,J=15.5Hz,1H),7.32-7.40(m,5H),7.45-7.50(m,4H),7.56(d,J=7.5Hz,4H),7.61(t,J=15.3Hz,3H),8.05(d,J=7.7Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.88,14.20,14.97,20.75,21.07,21.84,23.43,26.40,27.47,32.39,33.35,33.64,33.72,33.86,35.65,43.28,46.92,55.31,56.06,60.41,64.64,71.22,71.81,74.54,75.12,76.31,78.84,80.62,83.98,91.87,111.94,113.70,113.78,122.61,127.21,128.25,128.66,128.75,128.85,129.15,130.06,133.06,133.78,140.33,147.67,154.87,160.12,166.85,168.84,169.94,170.06,172.53,202.01.
7e:1HNMR(500MHz,CDCl3)δ(ppm):1.17(s,3H),1.20(s,3H),1.27(s,3H),1.45-1.49(m,2H),1.59-1.66(m,2H),1.82(s,3H),1.87(s,3H),1.72-2.06(m,7H),2.17(s,3H),2.19-2.40(m,5H),2.37(s,3H),2.56-2.64(m,1H),3.42(t,J=14.6Hz,1H)),3.92(d,J=9.6Hz,1H),4.20(d,J=9.1Hz,1H),4.32(d,J=7.7Hz,1H),4.87(s,1H),4.97(d,J=9.3Hz,1H),5.25(t,J=16.7Hz,1H),5.68(d,J=6.6Hz,1H),5.78(d,J=10.2Hz,1H),6.20(t,J=7.7Hz,1H),6.23(s,1H),7.22(t,J=7.5Hz,2H),7.26-7.30(m,2H),7.38(t,J=17.3Hz,1H),7.41-7.47(m,4H),7.53-7.58(m,5H),7.60-7.66(m,3H),7.83(d,J=4.8Hz,1H),8.16(d,J=8.3Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.63,14.28,21.77,22.57,22.44,27.52,28.46,29.69,33.35,34.45,34.59,34.77,35.59,43.31,46.97,54.82,56.19,71.16,72.36,73.49,74.51,75.65,76.74,78.82,81.00,83.88,111.66,112.41,123.70,127.35,128.25,128.45,129.35,129.72,129.96,130.05,130.18,133.05,133.78,137.85,140.87,154.86,158.49,166.84,168.79,170.41,172.04,173.03;
HR-MS:calcdforC55H60BrNO16([M+H]+),1070.3173;found,1070.3166;
实施例六：制备化合物3’-N-2-苯并呋喃基-7-对甲苯酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
2f:1HNMR(500MHz,CDCl3)δ(ppm):1.07(s,3H),1.16(s,3H),1.87-1.92(m,2H),1.94(s,3H),1.99(s,3H),2.14(s,3H),2.31(s,3H),2.39(s,3H),2.32-2.38(m,1H),2.75-2.82(m,2H),4.13(d,J=6.3Hz,1H),4.21(d,J=9.2Hz,1H),4.35(d,J=8.5Hz,1H),4.82(t,J=16.3Hz,1H),5.02(d,J=9.9Hz,1H),5.69(d,J=6.0Hz,1H),5.78(q,J=17.3Hz,1H),6.43(s,1H),7.20(d,J=9.3Hz,1H),7.49(t,J=15.3Hz,2H),7.61(t,J=16.5Hz,1H),7.80(d,J=7.5Hz,2H),8.10(d,J=9.5Hz,2H).13CNMR(125MHz,CDCl3)δ(ppm):11.08,14.20,15.00,20.48,21.03,21.15,21.73,21.86,26.38,43.30,46.77,55.31,56.30,60.41,64.66,71.85,71.91,74.66,74.78,78.88,80.64,84.04,91.90,111.95,113.72,113.80,122.62,123.75,126.62,127.23,127.46,128.26,128.67,128.78,128.88,128.91,129.22,129.84,130.08,133.35,133.78,140.38,143.43,147.69,154.88,160.14,165.32,166.86,168.28,169.97,202.45.
4f:1HNMR(500MHz,CDCl3)δ(ppm):3.87(s,3H),4.67(d,J=2.0Hz,1H),5.79(d,J=9.5Hz,1H),7.29-7.35(m,2H),7.38-7.46(m,3H),7.49-7.54(m,4H),7.67(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):30.33,53.33,54.36,73.19,111.15,111.94,122.74,123.77,127.01,128.08,128.80,138.49,148.09,158.28,173.19;
5f:1HNMR(500MHz,CDCl3)δ(ppm):3.80(s,3H),3.85(s,3H),5.01(s,1H),5.95(br,1H),6.90(d,J=8.5Hz,2H),7.13(br,1H),7.20-7.24(m,2H),7.30-7.39(m,4H),7.45(d,J=7.4Hz,2H),7.55(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):14.22,21.03,52.84,55.25,60.37,64.35,91.78,111.88,113.34,113.56,122.62,123.72,126.69,127.12,128.06,128.64,129.03,147.85,154.87,160.06,170.36;
6f:1HNMR(500MHz,CDCl3)δ(ppm):1.21(s,3H),1.25(s,3H),1.90-1.94(m,1H),1.96(s,3H),1.99(s,1H),2.07(s,3H),2.12(s,1H),2.18(s,3H),2.29-2.37(m,3H),2.40(s,3H),2.77-2.84(m,1H),3.84(s,3H),4.21(d,J=8.3Hz,1H),4.32(d,J=8.4Hz,1H),4.98(d,J=10.5Hz,1H),5.03(d,J=3.3Hz,1H),5.76(d,J=7.3Hz,H),5.81(q,J=18.5Hz,1H),6.04(s,1H),6.35(t,J=17.6Hz,1H),6.47(s,1H),6.94(d,J=9.8Hz,2H),7.23(d,J=7.7Hz,3H),7.33-7.40(m,6H),7.48(t,J=16.8Hz,4H),7.55-7.62(m,4H),7.85(d,J=8.6Hz,2H),8.08(d,J=7.4Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):11.08,14.20,15.00,20.48,21.03,21.15,21.73,21.86,26.38,33.36,35.75,43.30,46.77,55.31,56.30,60.41,64.66,71.85,71.91,74.66,74.78,76.36,78.88,80.64,84.04,91.90,111.95,113.80,122.62,123.75,126.62,127.23,127.46,128.26,128.67,128.88,128.91,129.22,129.84,130.08,133.35,133.78,140.38,143.43,147.69,154.88,160.14,165.32,166.86,168.28,169.97,170.06,202.45;
7f:1HNMR(500MHz,CDCl3)δ(ppm):1.21(s,6H),1.83-1.90(m,2H),1.95(s,6H),1.97(s,3H),1.98(s,3H),2.04-2.16(m,3H),2.37(d,J=9.7Hz,2H),2.41(s,3H),2.42(s,3H),2.74-2.82(m,1H),4.03(d,J=6.4Hz,1H),4.26(d,J=8.3Hz,1H),4.36(d,J=8.3Hz,1H),4.85(s,1H),5.00(d,J=10.4Hz,1H),5.31(s,1H),5.76(d,J=6.4Hz,2H),5.84(d,J=8.3Hz,1H),6.22(t,J=18.3Hz,1H),6.41(s,1H),7.22(t,J=7.5Hz,2H),7.26-7.30(m,2H),7.38(t,J=17.3Hz,1H),7.41-7.47(m,4H),7.53-7.58(m,5H),7.60-7.66(m,3H),7.83(d,J=4.8Hz,1H),8.16(d,J=8.3Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):11.06,14.72,20.50,20.89,21.73,22.58,26.54,29.70,33.45,35.64,43.23,46.86,54.51,56.41.71.94,72.09,73.38,74.47,74.90,76.49,78.55,81.11,83.99,111.39,112.01,123.80,127.16,127.27,127.37,127.44,128.36,128.75,12891,128.98,129.83,130.22,133.27,133.80,137.87,140.41,143.49,14787,15486,158.54,165.41,166.89,168.32,170.43,172.11,202.37;
HR-MS:calcdforC57H57NO16([M+H]+),1012.3755;found,1012.3748;
实施例七：制备化合物3’-N-2-噻吩基-7-正丁酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
2g:1HNMR(500MHz,CDCl3)δ(ppm):0.83(t,J=13.3Hz,3H),1.11(s,3H),1.13(s,3H),1.27-1.33(m,4H),1.80(s,3H),1.87(br,1H),2.10(s,3H),2.13(s,3H),2.18-2.37(m,3H),2.26(s,3H),2.54-2.63(m,1H),3.95(d,J=8.3Hz,1H),4.13(d,J=8.3Hz,1H),4.29(d,J=9.5Hz,1H),4.83(t,J=17.6Hz,1H),5.00(d,J=9.4Hz,1H),5.58-5.61(m,2H),6.28(s,1H),7.45(t,J=15.4Hz,2H),7.56(t,J=15.4Hz,1H),8.06(d,J=7.5Hz,1H);13CNMR(125MHz,CDCl3)δ(ppm):1.02,10.75,13.60,15.19,18.03,20.06,20.80,22.58,26.64,29.69,33.44,36.08,38.43,42.80,47.39,56.26,67.93,71.26,74.40,75.84,76.37,77.22,78.63,80.69,84.03,128.64,129.30,130.10,131.68,133.09,144.58,167.02,168.85,170.66,172.82,202.46;
4g:1HNMR(500MHz,CDCl3)δ(ppm):3.35(d,J=3.0Hz,2H),3.74(s,3H),4.63(br,1H),5.35(dd,J=2.0and2.2Hz,1H),6.21(dd,J=2.5and1.0Hz,1H),7.20(d,J=4.0Hz,2H),7.30(br,1H),7.35(t,J=15.5Hz,1H),7.51(t,J=15.3Hz,2H),7.52-7.56(m,2H);13CNMR(125MHz,CDCl3)δ(ppm):29.71,53.35,54.83,73.18,126.92,127.71,128.00,128.54,128.77,130.46,138.24,138.61,161.28,173.29;
5g:1HNMR(500MHz,CDCl3)δ(ppm):3.8(s,3H),3.84(s,3H),4.96(d,J=2.5Hz,1H),5.76(d,J=2.3Hz,1H),6.85(t,J=9.8Hz,1H),6.90(d,J=16.0Hz,2H),6.99(s,1H),7.05(d,J=4.0Hz,1H),7.34-7.39(m,5H),7.43(d,J=5.5Hz,1H),7.55(d,J=8.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):52.88,55.29,64.91,91.81,113.52,126.92,127.49,128.26,128.88,129.15,129.52,129.93,131.22,138.37,139.02,160.07,163.90,170.39;
6g:1HNMR(500MHz,CDCl3)δ(ppm):0.93(t,J=14.4Hz,3H),1.18(s,3H),1.24(s,3H),1.56-1.54(m,3H),1.80(s,3H),1.90(s,1H),2.07(s,6H),2.18(s,3H),2.14(s,3H),2.21-2.39(m,5H),2.56-2.66(m,1H),3.86(s,3H),3.99(d,J=7.6Hz,1H),4.14(d,J=9.3Hz,1H),4.28(d,J=8.5Hz,1H),4.92(d,J=9.6Hz,1H),4.96(s,1H),5.61(t,J=17.6Hz,1H),5.68(d,J=16.5Hz,1H),5.99(s,1H),6.31(s,2H),6.87(t,J=9.5Hz,2H),7.20(d,J=8.6Hz,2H),7.02(s,1H),7.08(d,J=2.5Hz,1H),7.40(d,J=7.6Hz,4H),7.44(d,J=5.4Hz,1H),7.48(t,J=15.6Hz,2H),7.56(d,J=8.4Hz,2H),7.61(t,J=15.2Hz,1H),8.04(d,J=8.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.86,13.62,14.89,18.04,20.72,21.07,21.83,24.93,25.61,26.41,33.35,33.90,35.61,36.04,43.28,46.85,55.34,56.10,65.04,71.00,71.78,74.56,75.11,76.32,78.90,80.60,84.01,91.89,113.79,127.79,127.14,127.48,128.37,128.65,128.96,129.00,129.14,129.27,130.07,130.16,131.36,132.97,133.77,138.03,140.40,160.19,163.72,166.92,168.73,169.76,170.04,172.67,202.05
7g:1HNMR(500MHz,CDCl3)δ(ppm):0.93(t,J=16.3Hz,3H),1.18(s,3H),1.20(s,3H),1.27(s,2H),1.58-1.64(m,3H),1.83(s,3H),1.86(s,3H),1.94(s,1H),2.16(s,3H),2.02-2.13(m,1H),2.32-2.37(m,1H),2.17(s,3H),2.20-2.36(m,4H),2.37(s,3H),2.57-2.64(m,1H),3.92(d,J=7.4Hz,1H),4.21(d,J=9.2Hz,1H),4.32(d,J=9.3Hz,1H),4.81(s,1H),4.95(d,J=9.6Hz,1H),5.56(q,J=7.6Hz,1H),5.68(d,J=7.4Hz,1H),5.79(d,J=10.3Hz,1H),6.19(t,J=8.3Hz,1H),6.26(s,1H),7.02-7.09(m,2H),7.36(t,J=15.3Hz,1H),7.42(t,J=15.5Hz,2H),7.47-7.58(m,5H),7.64(t,J=14.3Hz,1H),8.12(d,J=8.3Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):0.82,13.60,14.71,18.02,20.74,22.55,26.55,29.70,33.47,35.58,36.06,43.21,46.99,54.76,56.24,71.10,72.07,73.27,74.31,75.26,76.46,78.42,81.13,83.91,127.07,127.82,128.29,128.66,128.74,128.95,129.09,130.68,133.06,133.78,138.01,140.25,161.44,166.86,168.86,170.47,172.15,172.89,201.92;
HR-MS:calcdforC49H55NO15S([M+H]+),930.3370;found,930.3360;
实施例八：制备化合物3’-N-2-噻吩基-7-正己酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
2h:1HNMR(500MHz,CDCl3)δ(ppm):0.87(t,J=14.3Hz,3H),1.06(s,3H),1.12(s,3H),1.27-1.33(m,3H),1.52-1.60(m,2H),1.79(s,3H),1.87(br,1H),2.09(s,3H),2.15(s,3H),2.18-2.37(m,3H),2.28(s,3H),2.55-2.62(m,1H),3.99(d,J=8.5Hz,1H),4.14(d,J=8.4Hz,1H),4.30(d,J=9.3Hz,1H),4.83(t,J=17.6Hz,1H),4.97(d,J=9.6Hz,1H),5.58-5.61(m,2H),6.28(s,1H),7.47(t,J=15.5Hz,2H),7.60(t,J=15.6Hz,1H),8.09(d,J=7.7Hz,1H);13CNMR(125MHz,CDCl3)δ(ppm):10.73,13.89,14.16,15.18,20.12,20.77,21.02,22.25,22.51,24.14,26.57,31.15,34.11,38.58,42.75,47.39,56.15,60.42,71.33,74.44,75.84,76.32,76.81,166.90,168.90,170.64,173.12,202.52;
4h:1HNMR(500MHz,CDCl3)δ(ppm):3.35(d,J=3.0Hz,2H),3.74(s,3H),4.63(br,1H),5.35(dd,J=2.0and2.2Hz,1H),6.21(dd,J=2.5and1.0Hz,1H),7.20(d,J=4.0Hz,2H),7.30(br,1H),7.35(t,J=15.5Hz,1H),7.51(t,J=15.3Hz,2H),7.52-7.56(m,2H);13CNMR(125MHz,CDCl3)δ(ppm):29.71,53.35,54.83,73.18,126.92,127.71,128.00,128.54,128.77,130.46,138.24,138.61,161.28,173.29;
5h:1HNMR(500MHz,CDCl3)δ(ppm):3.8(s,3H),3.84(s,3H),4.96(d,J=2.5Hz,1H),5.76(d,J=2.3Hz,1H),6.85(t,J=9.8Hz,1H),6.90(d,J=16.0Hz,2H),6.99(s,1H),7.05(d,J=4.0Hz,1H),7.34-7.39(m,5H),7.43(d,J=5.5Hz,1H),7.55(d,J=8.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):52.88,55.29,64.91,91.81,113.52,126.92,127.49,128.26,128.88,129.15,129.52,129.93,131.22,138.37,139.02,160.07,163.90,170.39;
6h:1HNMR(500MHz,CDCl3)δ(ppm):0.89(t,J=14.3Hz,3H),1.17(s,3H),1.23(s,3H),1.25-1.34(m,7H),1.52-1.64(m,3H),1.80(s,3H),2.06(s,6H),2.18(s,3H),2.17(s,3H),2.21-2.40(m,5H),2.56-2.64(m,1H),3.84(s,3H),3.98(d,J=7.4Hz,1H),4.14(d,J=8.6Hz,1H),4.27(d,J=9.3Hz,1H),4.91(d,J=10.2Hz,1H),4.96(d,J=3.2Hz,1H),5.61(q,J=16.5Hz,1H),5.68(d,J=7.3Hz,1H),5.91(d,J=2.3Hz,1H),6.31(s,2H),6.86(t,J=9.6Hz,2H),6.94(d,J=9.3Hz,2H),7.01(s,1H),7.08(d,J=4.2Hz,1H),7.36-7.48(m,9H),7.53-7.62(m,3H),8.04(d,J=8.8Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.86,13.93,14.89,20.72,21.09,21.83,22.29,24.13,26.40,29.68,31.18,33.32,34.07,35.64,43.28,46.85,55.34,56.07,65.06,71.02,71.79,74.57,75.10,76.31,78.83,80.60,84.01,91.88,113.79,127.13,127.49,128.38,128.64,128.96,129.01,030.05,130.18,131.38,133.01,133.75,137.98,140.38,160.19,163.73,166.84,168.75,169.81,170.05,172.90,202.04.
7h:1HNMR(500MHz,CDCl3)δ(ppm):0.90(t,J=15.5Hz,3H),1.18(s,3H),1.20(s,3H),124-1.34(m,6H),1.82(s,3H),1.89(s,3H),1.95(s,1H),2.15(s,3H),2.21-2.36(m,4H),2.39(s,3H),2.60(br,1H),3.94(s,1H),4.03(s,1H),4.20(d,J=8.8Hz,1H),4.31(d,J=8.8Hz,1H)，4.82(s,1H),4.95(d,J=9Hz,1H),5.55(t,J=16.6Hz,1H),5.68(d,J=6Hz,1H),5.78(d,J=10.3Hz,1H),6.18(t,J=7Hz,1H),6.25(s,1H),7.05(s,1H),7.12(d,J=6Hz,1H),7.0-7.62(m,9H),8.11(d,J=7Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.82,13.91,14.68,20.74,20.80,22.27,22.57,24.15,26.52,29.09,31.17,33.42,34.10,35.60,43.21,46.98,54.95,56.19,71.12,71.99,73.31,74.34,75.24,76.44,78.40,81.10,83.92,127.08,127.83,128.25,128.71,128.74,128.92,129.14,130.17,130.70,133.03,133.75,138.04,140.30,161.54,166.82,168.87,170.49,172.20,173.10,201.92;
HR-MS:calcdforC51H59NO15S([M+H]+),958.3683;found,958.3672;
实施例九：制备化合物3’-N-2-噻吩基-7-2-噻吩酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
2i:1HNMR(500MHz,CDCl3)δ(ppm):1.07(s,3H),1.15(s,3H),1.83(br,1H),1.91(s,3H),1.94-1.98(m,1H),2.01(s,3H),2.14(s,3H),2.31(s,3H),2.28-2.34(m,2H),2.60(br,1H),2.74-2.81(m,1H),4.07(d,J=7.3Hz,1H),4.20(d,J=8.2Hz,1H),4.35(d,J=8.4Hz,1H),4.86(t,J=16.5Hz,1H),5.01(d,J=9.4Hz,1H),5.68(d,J=7.4Hz,1H),5.74(q,J=17.4Hz,1H),6.44(s,1H),7.07(q,J=9.4Hz,1H),7.49(t,J=16.8Hz,2H),7.54(dd,J=4.2Hz,J=1.3Hz,1H),7.61(t,J=14.3Hz,1H),7.74(dd,J=4.6Hz,J=1.4Hz,1H),8.12(d,J=7Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.86,14.19,15.21,20.17,20.59,22.54,26.59,33.44,38.59,42.85,47.20,53.46,56.34,60.43,67.73,72.54,74.48,75.51,76.36,78.69,80.52,83.96,127.53,128.66,129.33,130.10,131.66,132.58,133.60,133.71,145.01,160.95,166.98,168.52,170.72,202.58;
4i:1HNMR(500MHz,CDCl3)δ(ppm):3.35(d,J=3.0Hz,2H),3.74(s,3H),4.63(br,1H),5.35(dd,J=2.0and2.2Hz,1H),6.21(dd,J=2.5and1.0Hz,1H),7.20(d,J=4.0Hz,2H),7.30(br,1H),7.35(t,J=15.5Hz,1H),7.51(t,J=15.3Hz,2H),7.52-7.56(m,2H);13CNMR(125MHz,CDCl3)δ(ppm):29.71,53.35,54.83,73.18,126.92,127.71,128.00,128.54,128.77,130.46,138.24,138.61,161.28,173.29;
5i:1HNMR(500MHz,CDCl3)δ(ppm):3.8(s,3H),3.84(s,3H),4.96(d,J=2.5Hz,1H),5.76(d,J=2.3Hz,1H),6.85(t,J=9.8Hz,1H),6.90(d,J=16.0Hz,2H),6.99(s,1H),7.05(d,J=4.0Hz,1H),7.34-7.39(m,5H),7.43(d,J=5.5Hz,1H),7.55(d,J=8.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):52.88,55.29,64.91,91.81,113.52,126.92,127.49,128.26,128.88,129.15,129.52,129.93,131.22,138.37,139.02,160.07,163.90,170.39;
6i:1HNMR(500MHz,CDCl3)δ(ppm):1.20(s,3H),1.24(s,3H),1.54-1.71(m,1H),1.91(s,3H),1.94-2.00(m,11H),2.09(s,3H),2.11(s,3H),2.25-2.35(m,2H),2.74-2.82(m,1H),3.86(s,3H),4.05(d,J=7.3Hz,1H),4.19(d,J=8.5Hz,1H),4.31(d,J=9.5Hz,1H),4.93-4.99(m,2H),5.73(d,J=7.2Hz,1H),5.92(d,J=2.5Hz,1H),6.31(t,J=18.3Hz,1H),6.46(s,1H),6.87(t,J=9.4Hz,2H),6.96(d,J=9.5Hz,2H),7.03(s,1H),7.07-7.10(m,2H),7.37-7.46(m,7H),7.48(t,J=17.7Hz,2H),7.54-7.64(m,4H),7.76(d,J=4.2Hz,1H),7.08(d,J=4.2Hz,1H),8.07(d,J=8.8Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.98,14.20,14.92,20.51,21.14,21.85,26.38,33.37,35.70,43.27,46.64,55.35,56.23,60.42,65.05,71.79,72.22,74.62,74.76,7893,80.54,83.97,91.91,113.81,127.15,127.49,127.54,128.39,128.68,128.97,129.03,129.27,130.08,130.19,131.39,132.60,133.22,133.57,133.76,133.80,137.99,140.48,160.21,163.73,168.36,169.91,170.05,202.10;
7i:1H-NMR(CDCl3,500MHz)δppm:1.18(s,3H),1.28(s,1H),1.89(s,3H),1.93(s,3H),2.02(s,3H),2.22(s,1H),2.32(s,2H),2.39(s,3H),2.72-2.79(m,1H),3.99(d,J=6.6Hz,1H),4.17(s,1H),4.25(d,J=8.4Hz,1H),4.34(d,J=8.3Hz,2H),4.82(s,1H),4.98(d,J=9.1Hz,1H),5.69(t,J=8.6Hz,1H),5.73(d,J=6.6Hz,1H),5.78(d,J=8.05Hz,1H),6.19(t,J=8.22Hz,1H),6.39(s,1H),7.06(d,J=21.6Hz,2H),7.20(d,J=8.8Hz,2H),7.34(d,J=7.1Hz,1H),7.40(t,J=7.3Hz,2H),7.45-7.49(m,3H),7.51-7.55(m,4H),7.63(t,J=7.1Hz,1H),7.74(s,1H),8.13(d,J=7.4Hz,2H).13C-NMR(CDCl3,125MHz)δppm:1.04,10.97,14.63,20.55,20.96,22.55,26.46,29.70,33.44,35.67,43.21,46.76,54.99,56.31,71.92,72.33,73.31,74.43,74.90,76.44,78.48,80.96,83.88,127.07,127.60,127.86,128.23,128.75,128.78,128.91,129.72,130.20,130.75,132.74,133.19,133.46,133.77,133.82,138.02,138.06,140.45,160.95,161.67,166.84,168.52,170.59,172.32,201.99.
HR-MS:calcdforC50H51NO15S2([M+H]+),970.2778;found,970.2775;
实施例十：制备化合物3’-N-2-噻吩基-7-2-乙基己酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
2j:1HNMR(500MHz,CDCl3)δ(ppm):0.78-0.94(m,8H),1.04(s,3H),1.14(s,3H),1.18-1.31(m,3H),1.36-1.65(m,5H),2.13(s,3H),2.16(s,3H),2.28(s,3H),2.22-2.31(m,2H),2.56-2.64(m,1H),4.00(d,J=6.6Hz,1H),4.16(d,J=7.6Hz,1H),4.31(d,J=8.6Hz,1H),4.82(t,J=17.6Hz,1H),4.31(d,J=9.6Hz,1H),5.56(t,J=18.6Hz,1H),5.64(d,J=6.6Hz,1H),6.41(s,1H),7.47(t,J=15.5Hz,2H),7.60(t,J=15.4Hz,1H),8.10(d,J=9.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.81,11.08,11.36,13.90,14.16,15.02,20.11,20.78,22.51,22.60,23.67,23.92,26.52,28.85,28.99,29.70,30.32,33.41,38.51,42.68,45.98,46.03,47.29,56.55,60.44,67.65,71.19,71.22,74.49,75.89,76.37,78.61,80.49,83.85,128.62,129.35,130.08,131.56,133.65,145.10,166.93,168.81,170.70,175.02,202.52;
4j:1HNMR(500MHz,CDCl3)δ(ppm):3.35(d,J=3.0Hz,2H),3.74(s,3H),4.63(br,1H),5.35(dd,J=2.0and2.2Hz,1H),6.21(dd,J=2.5and1.0Hz,1H),7.20(d,J=4.0Hz,2H),7.30(br,1H),7.35(t,J=15.5Hz,1H),7.51(t,J=15.3Hz,2H),7.52-7.56(m,2H);13CNMR(125MHz,CDCl3)δ(ppm):29.71,53.35,54.83,73.18,126.92,127.71,128.00,128.54,128.77,130.46,138.24,138.61,161.28,173.29;
5j:1HNMR(500MHz,CDCl3)δ(ppm):3.8(s,3H),3.84(s,3H),4.96(d,J=2.5Hz,1H),5.76(d,J=2.3Hz,1H),6.85(t,J=9.8Hz,1H),6.90(d,J=16.0Hz,2H),6.99(s,1H),7.05(d,J=4.0Hz,1H),7.34-7.39(m,5H),7.43(d,J=5.5Hz,1H),7.55(d,J=8.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):52.88,55.29,64.91,91.81,113.52,126.92,127.49,128.26,128.88,129.15,129.52,129.93,131.22,138.37,139.02,160.07,163.90,170.39;
6j:1HNMR(500MHz,CDCl3)δ(ppm):0.81-0.93(m,7H),1.20(s,3H),1.21(s,3H),1.25-1.33(m,4H),1.40-1.68(m,7H),1.81(s,3H),2.08(s,3H),2.15(s,6H),2.23-2.32(m,3H),2.58-2.66(m,1H),3.85(s,3H),3.99(d,J=7.3Hz,1H),4.15(d,J=9.5Hz,1H),4.29(d,J=9.3Hz,1H),4.91(d,J=8.2Hz,1H),4.96(s,1H),5.57(t,J=17.5Hz,1H),5.70(d,J=6.3Hz,1H),5.91(s,1H),6.29(t,J=17.2Hz,2H),6.86(s,1H),6.94(d,J=8.3Hz,2H),7.01(s,1H),7.08(d,J=4.2Hz,1H),7.36-7.48(m,9H),7.53-7.62(m,3H),806(d,J=8.8Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.94,11.11,11.41,13.95,14.78,20.71,21.07,21.84,22.65,23.63,23.92,24.92,26.33,28.86,29.01,30.31,33.39,33.86,35.63,43.20,45.88,45.96,46.60,55.34,56.42,56.46,65.01,70.86,71.76,74.64,75.05,76.37,78.88,80.51,83.88,91.89,113.78,127.13,127.47,128.36,128.65,128.96,129.03,129.16,129.26,130.06,130.17,131.37,133.16,133.77,138.00,140.48,160.18,163.17,166.90,168.52,168.57,169.80,169.99,174.72,202.08;
7j:1HNMR(500MHz,CDCl3)δ(ppm):0.79-0.93(m,3H),1.16(s,3H),1.19(s,3H),1.25-1.65(m,9H),1.82(s,3H),1.83(s,3H),1.92(s,3H),2.14(s,3H),2.24-2.33(m,3H),2.37(s,3H),2.56-2.64(m,1H),3.93(d,J=8.3Hz,1H),4.07(br,1H),4.21(d,J=9.3Hz,1H),4.32(d,J=7.7Hz,1H),4.82(s,1H),4.93(d,J=9.3Hz,1H),5.51(t,J=16.6Hz,1H),5.70(d,J=6.6Hz,1H),5.78(d,J=10.6Hz,1H),6.17(t,J=7.5Hz,1H),6.38(s,1H),7.04(t,J=8.2Hz,1H),7.13(d,J=10.3Hz,1H),7.33(d,J=16.3Hz,1H),7.40(t,J=14.3Hz,1H),7.44-7.56(m,5H),7.62(t,J=15.3Hz,1H),8.13(d,J=7.3Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.91,11.08,11.38,13.93,14.53,20.72,20.73,20.83,22.54,22.63,23.59,23.83,2645,28.84,28.99,29.61,29.69,30.22,33.47,35.60,43.14,45.86,45.95,46.73,54.83,56.51,56.54,71.97,73.27,74.42,78.43,80.98,83.80,127.05,127.81,128.68,128.74,128.91,129.51,130.18,130.69,133.19,138.02,138.06,140.36,161.55,166.84,168.68,170.46,172.46,172.21,174.92,175.01,201.95;
HR-MS:calcdforC53H63NO15S([M+H]+),986.3996;found,986.3976;
实施例十一：制备化合物3’-N-2-噻吩基-7-溴代己酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
2k:1HNMR(500MHz,CDCl3)δ(ppm):1.07(s,3H),1.12(s,3H),1.40-1.52(m,3H),1.56-1.68(m,3H),1.72(s,3H),1.82-1.90(m,3H),2.09(s,3H),2.16(s,3H),2.20-2.27(m,1H),2.28(s,3H),2.32-2.41(m,2H),3.40(t,J=13.4Hz,2H),3.99(d,J=6Hz,1H),4.15(d,J=9.2Hz,1H),4.31(d,J=8.5Hz,1H),4.82(t,J=16.5Hz,1H),4.97(d,J=9.2Hz,1H),5.61(m,2H),6.27(s,1H),7.48(t,J=15.3Hz,2H),7.61(t,J=15.5Hz,1H),8.10(d,J=9.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.75,14.18,15.21,20.11,20.83,22.54,23.43,23.84,26.61,27.45,27.57,32.35,33.37,33.45,33.61,33.77,38.53,42.75,47.40,56.15,60.46,67.72,71.49,74.41,75.83,76.33,78.60,80.59,83.97,128.64,129.30,130.08,131.44,133.69,144.91,166.94,169.01,170.73,172.72,202.48.
4k:1HNMR(500MHz,CDCl3)δ(ppm):3.35(d,J=3.0Hz,2H),3.74(s,3H),4.63(br,1H),5.35(dd,J=2.0and2.2Hz,1H),6.21(dd,J=2.5and1.0Hz,1H),7.20(d,J=4.0Hz,2H),7.30(br,1H),7.35(t,J=15.5Hz,1H),7.51(t,J=15.3Hz,2H),7.52-7.56(m,2H);13CNMR(125MHz,CDCl3)δ(ppm):29.71,53.35,54.83,73.18,126.92,127.71,128.00,128.54,128.77,130.46,138.24,138.61,161.28,173.29;
5k:1HNMR(500MHz,CDCl3)δ(ppm):3.8(s,3H),3.84(s,3H),4.96(d,J=2.5Hz,1H),5.76(d,J=2.3Hz,1H),6.85(t,J=9.8Hz,1H),6.90(d,J=16.0Hz,2H),6.99(s,1H),7.05(d,J=4.0Hz,1H),7.34-7.39(m,5H),7.43(d,J=5.5Hz,1H),7.55(d,J=8.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):52.88,55.29,64.91,91.81,113.52,126.92,127.49,128.26,128.88,129.15,129.52,129.93,131.22,138.37,139.02,160.07,163.90,170.39;
6k:1HNMR(500MHz,CDCl3)δ(ppm):1.17(s,3H),1.24(s,3H),1.42-1.50(m,2H),1.57-1.70(m,3H),1.80(s,3H),1.83-1.91(m,3H),2.06(s,6H),2.18(s,3H),2.22-2.31(m,3H),2.36-2.43(m,1H),2.56-2.64(m,1H),3.42(t,J=14.3Hz,2H),3.85(s,3H),3.98(d,J=7.3Hz,1H),4.14(d,J=9.5Hz,1H),4.28(d,J=8.3Hz,1H),4.91(d,J=10.2Hz,1H),4.96(s,1H),5.60(q,J=8.5Hz,1H),5.67(d,J=7.3Hz,1H),5.91(d,J=2.1Hz,1H),6.28(s,1H),6.86(t,J=8.5Hz,1H),6.96(d,J=8.6Hz,2H),7.01(s,1H),7.08(d,J=5.2Hz,1H),7.36-7.48(m,8H),7.56(d,J=8.6Hz,2H),7.61(t,J=4.5Hz,1H0),8.06(d,J=8.8Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.87,14.9,20.76,21.09,21.83,23.42,24.93,26.40,27.47,32.38,33.33,33.66,33.73,33.87,35.62,43.27,46.86,55.35,56.06,65.07,71.18,71.77,74.54,75.11,76.30,78.85,80.58,83.98,91.87,113.78,127.12,127.50,128.38,128.66,128.97,129.01,129.13,129.25,130.06,130.18,131.39,132.96,133.78,137.99,140.40,160.19,163.75,166.87,168.83,169.85,170.07,172.50,202.03;
7k:1HNMR(CDCl3,500MHz)δ(ppm):1.18(s,3H),1.20(s,3H),1.27(s,3H),1.42-1.49(m,2H),1.57-1.66(m,2H),1.82(s,3H),1.85(s,3H),1.7-2.06(m,7H),2.17(s,3H),2.21-2.40(m,5H),2.37(s,3H),2.56-2.64(m,1H),3.42(t,J=14.3Hz,1H)),3.92(d,J=9.3Hz,1H),4.20(d,J=9.3Hz,1H),4.32(d,J=7.7Hz,1H),4.82(s,1H),4.95(d,J=9.3Hz,1H),5.57(t,J=16.6Hz,1H),5.68(d,J=6.6Hz,1H),5.78(d,J=10.2Hz,1H),6.20(t,J=7.7Hz,1H),6.23(s,1H),7.04-7.12(m,2H),7.35(t,J=13.7Hz,1H),7.42(t,J=7.7Hz,2H),7.46-7.56(m,7H),7.63(t,J=7.7Hz,1H),8.13(d,J=7.3Hz,2H);13C-NMR(125MHz,CDCl3)δ(ppm):10.83,14.68,20.77,22.54,23.44,26.52,27.46,29.69,32.35,33.45,33.59,33.77,35.59,43.21,46.97,54.82,56.19,71.26,72.06,73.29,74.31,75.25,76.44,78.42,81.008,83.88,127.07,127.81,128.66,128.79,128.93,129.10,130.17,130.69,133.01,133.78,138.03,140.31,161.48,166.84,168.94,170.48,172.20,172.66,201.91;
HR-MS:calcdforC51H58BrNO15S([M+Na]+),1036.2789,found1036.2884;
实施例十二：制备化合物3’-N-2-噻吩基-7-对甲苯酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
2l:1HNMR(500MHz,CDCl3)δ(ppm):1.07(s,3H),1.16(s,3H),1.87-1.92(m,2H),1.94(s,3H),1.99(s,3H),2.14(s,3H),2.31(s,3H),2.39(s,3H),2.32-2.38(m,1H),2.75-2.82(m,2H),4.13(d,J=6.3Hz,1H),4.21(d,J=9.2Hz,1H),4.35(d,J=8.5Hz,1H),4.82(t,J=16.3Hz,1H),5.02(d,J=9.9Hz,1H),5.69(d,J=6.0Hz,1H),5.78(q,J=17.3Hz,1H),6.43(s,1H),7.20(d,J=9.3Hz,1H),7.49(t,J=15.3Hz,2H),7.61(t,J=16.5Hz,1H),7.80(d,J=7.5Hz,2H),8.10(d,J=9.5Hz,2H).13CNMR(125MHz,CDCl3)δ(ppm):11.08,14.20,15.00,20.48,21.03,21.15,21.73,21.86,26.38,43.30,46.77,55.31,56.30,60.41,64.66,71.85,71.91,74.66,74.78,78.88,80.64,84.04,91.90,111.95,113.72,113.80,122.62,123.75,126.62,127.23,127.46,128.26,128.67,128.78,128.88,128.91,129.22,129.84,130.08,133.35,133.78,140.38,143.43,147.69,154.88,160.14,165.32,166.86,168.28,169.97,202.45.
4l:1HNMR(500MHz,CDCl3)δ(ppm):3.35(d,J=3.0Hz,2H),3.74(s,3H),4.63(br,1H),5.35(dd,J=2.0and2.2Hz,1H),6.21(dd,J=2.5and1.0Hz,1H),7.20(d,J=4.0Hz,2H),7.30(br,1H),7.35(t,J=15.5Hz,1H),7.51(t,J=15.3Hz,2H),7.52-7.56(m,2H);13CNMR(125MHz,CDCl3)δ(ppm):29.71,53.35,54.83,73.18,126.92,127.71,128.00,128.54,128.77,130.46,138.24,138.61,161.28,173.29;
5l:1HNMR(500MHz,CDCl3)δ(ppm):3.8(s,3H),3.84(s,3H),4.96(d,J=2.5Hz,1H),5.76(d,J=2.3Hz,1H),6.85(t,J=9.8Hz,1H),6.90(d,J=16.0Hz,2H),6.99(s,1H),7.05(d,J=4.0Hz,1H),7.34-7.39(m,5H),7.43(d,J=5.5Hz,1H),7.55(d,J=8.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):52.88,55.29,64.91,91.81,113.52,126.92,127.49,128.26,128.88,129.15,129.52,129.93,131.22,138.37,139.02,160.07,163.90,170.39;
6l:1HNMR(500MHz,CDCl3)δ(ppm):1.21(s,3H),1.24(s,3H),1.94(s,3H),2.00(s,3H),2.09(s,6H),2.11(s,3H),2.26-2.36(m,2H),2.40(s,3H),2.75-2.83(m,1H),3.86(s,3H),4.07(d,J=6.3Hz,1H),4.20(d,J=8.5Hz,1H),4.32(d,J=8.3Hz,1H),4.94-4.99(m,2H),5.73-5.80(m,2H),5.93(d,J=3.2Hz,1H),6.32(t,J=18.3Hz,1H),6.45(s,1H),6.87(t,J=9.5Hz,1H),6.96(d,J=8.6Hz,2H),7.03(s,1H),7.09(d,J=5.2Hz,1H),7.22(d,J=8.2Hz,1H)),7.34-7.45(m,6H),7.48(d,J=15.6Hz,2H),7.56-7.63(m,3H),7.84(d,J=8.5Hz,2H),8.06(d,J=8.8Hz,2H);13C-NMR(125MHz,CDCl3)δ(ppm):11.07,14.20,14.93,20.48,21.04,21.16,21.72,21.85,24.94,25.61,26.38,29.69,33.33,33.88,35.71,43.28,46.69,55.35,56.28,60.41,65.07,71.80,71.86,74.66,74.76,76.35,78.91,80.60,84.04,91.91,113.81,127.15,127.44,127.49,128.38,128.67,128.89,128.97,129.03,129.19,129.27,129.84,130.08,130.19,131.39,133.25,133.78,137.99,140.46,143.41,160.21,163.73,165.29,166.90,168.28,169.87,170.06,202.47;
7l:1HNMR(500MHz,CDCl3)δ(ppm):1.19(s,6H),1.28(s,2H),1.82-1.87(m,1H),1.91(s,3H),1.97(s,3H),2.00(s,3H),2.16(s,2H),2.32-2.36(m,2H),2.40(s,3H),2.41(s,3H),2.74-2.82(m,1H),4.01(d,J=6.8Hz,1H),4.12(br,1H),4.26(d,J=8.6Hz,1H),4.35(d,J=9.0Hz,1H),4.83(s,1H),4.99(d,J=10.4Hz,1H),5.69-5.82(m,3H),6.17-6.24(m,1H),6.39(s,3H),7.04(t,J=8.3Hz,1H),7.14-7.24(m,3H),7.34(t,J=15.3Hz,1H),7.41(t,J=14.3Hz,2H),7.45-7.56(m,6H),7.61(t,J=17.3Hz,1H),7.83(d,J=7.3Hz,1H),8.14(d,J=8.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):11.05,14.67,20.51,20.93,21.73,22.56,26.48,29.70,33.42,35.67,43.21,46.82,54.92,56.39,71.96,71.97,73.32,74.46,74.90,74.47,76.47,78.51,81.06,83.96,127.07,127.34,127.84,128.25,128.71,128.77,128.92,129.16,129.82,130.20,130.71,133.23,133.77,138.04,138.07,140.41,143.53,161.59,165.46,166.89,168.41,170.53,172.28,202.35;
HR-MS:calcdforC53H55NO15S([M+H]+),978.3370;found,978.3360;
实施例十三：制备化合物3’-N-4-氯甲苯基-7-丁酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
2m:1HNMR(500MHz,CDCl3)δ(ppm):0.83(t,J=13.3Hz,3H),1.11(s,3H),1.13(s,3H),1.27-1.33(m,4H),1.80(s,3H),1.87(br,1H),2.10(s,3H),2.13(s,3H),2.18-2.37(m,3H),2.26(s,3H),2.54-2.63(m,1H),3.95(d,J=8.3Hz,1H),4.13(d,J=8.3Hz,1H),4.29(d,J=9.5Hz,1H),4.83(t,J=17.6Hz,1H),5.00(d,J=9.4Hz,1H),5.58-5.61(m,2H),6.28(s,1H),7.45(t,J=15.4Hz,2H),7.56(t,J=15.4Hz,1H),8.06(d,J=7.5Hz,1H);13CNMR(125MHz,CDCl3)δ(ppm):1.02,10.75,13.60,15.19,18.03,20.06,20.80,22.58,26.64,29.69,33.44,36.08,38.43,42.80,47.39,56.26,67.93,71.26,74.40,75.84,76.37,77.22,78.63,80.69,84.03,128.64,129.30,130.10,131.68,133.09,144.58,167.02,168.85,170.66,172.82,202.46;
4m:1HNMR(500MHz,CDCl3)(ppm):3.84(s,3H),4.60(s,1H),4.65(d,J=1.0Hz,1H),5.75(d,J=9.5Hz,1H),7.13(d,J=9.0Hz,1H),7.3(t,J=14.4Hz,1H),7.38(t,J=15.6Hz,2H),7.45(t,J=16.0Hz,4H),7.77(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):45.33,53.27,54.98,73.25,126.91,127.60,128.00,128.77,133.93,138.57,141.16,166.44,173.38;
5m:1HNMR(500MHz,CDCl3)δ(ppm):3.80(s,3H),3.85(s,3H),5.01(s,1H),5.95(br,1H),6.90(d,J=8.5Hz,2H),7.13(br,1H),7.20-7.24(m,2H),7.30-7.39(m,4H),7.45(d,J=7.4Hz,2H),7.55(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):14.22,21.03,52.84,55.25,60.37,64.35,91.78,111.88,113.34,113.56,122.62,123.72,126.69,127.12,128.06,128.64,129.03,147.85,154.87,160.06,170.36;
6m:1HNMR(500MHz,CDCl3)δ(ppm):0.93(t,J=14.3Hz,3H),1.19(s,3H),1.25(s,3H),1.27(s,2H),1.58-1.67(m,3H),1.80(s,3H),2.07(s,6H),2.18(s,3H),2.19(s,3H),2.21-2.29(m,4H),2.32-2.40(m,1H),2.57-2.64(m,1H),3.86(s,3H),3.99(d,J=7.3Hz,1H),4.14(d,J=9.8Hz,1H),4.28(d,J=8.4Hz,1H),4.51(s,2H),4.92(d,J=9.3Hz,1H),5.61(t,J=17.3Hz,1H),5.68(d,J=16.2Hz,1H),5.99(s,1H),6.31(s,2H),6.90(br,2H),7.23-7.30(m,6H),7.36(s,3H),7.46(t,J=15.5Hz,3H),7.60(t,J=15.6Hz,1H),8.04(d,J=8.6Hz,2H);13C-NMR(125MHz,CDCl3)δ(ppm):10.86,13.62,14.84,18.00,20.75,21.03,21.86,26.42,33.35,36.04,43.30,45.41,46.90,55.33,56.10,71.10,71.60,74.55,75.14,76.29,78.79,80.63,84.00,113.79,127.26,127.49,128.34,128.41,128.66,133.11,133.77,135.41,140.33,160.09,166.87,168.77,169.80,169.92,172.71,202.01;
7m:1H-NMR(CDCl3,500MHz)δppm:0.90(t,J=7.02Hz,3H),1.18(s,3H),1.20(s,3H),1.27(s,3H),1.57-1.62(m,3H),1.83(s,3H),1.84(s,3H),2.01(s,1H),2.17(s,3H),2.39(s,3H),2.59-2.63(m,1H),3.82(s,1H),3.93(d,J=6.8Hz,1H),4.01(d,J=6.0Hz,1H),4.11-4.15(m,1H),4.20(d,J=8.4Hz,1H),4.32(d,J=8.8Hz,1H),4.59(s,2H),4.80(s,1H),4.96(d,J=8.8Hz,1H),5.54-5.58(m,1H),5.68(d,J=6.8Hz,1H),5.80-5.82(m,1H),6.18(d,J=17.4Hz,1H),6.25(s,1H),7.29(t,J=11.5Hz,2H),7.35-7.37(m,2H),7.39-7.45(m,5H),7.48-7.53(m,4H),7.63(t,J=7.4Hz,1H),7.77(d,J=8.2Hz,1H),8.12(d,J=7.3Hz,2H).13CNMR(125MHz,CDCl3)δ(ppm):10.82,13.91,14.19,14.62,20.73,20.81,21.04,22.28,22.54,24.15,26.52,29.69,31.17,34.09,43.23,45.29,46.96,55.01,56.18,60.42,71.09,71.97,73.30,74.36,75.23,78.44,81.07,83.93,126.91,127.07,127.60,128.25,128.71,127.74,128.77,128.80,128.92,129.13,130.16,133.00,133.62,133.76,138.06,140.34,141.24,166.83,170.38,172.28,173.06,201.92;
HR-MS:calcdforC52H58ClNO15([M+H]+),972.3573;found,972.3568;
实施例十四：制备化合物3’-N-4-氯甲苯基-7-己酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
2n:1HNMR(500MHz,CDCl3)δ(ppm):0.87(t,J=14.3Hz,3H),1.06(s,3H),1.12(s,3H),1.27-1.33(m,3H),1.52-1.60(m,2H),1.79(s,3H),1.87(br,1H),2.09(s,3H),2.15(s,3H),2.18-2.37(m,3H),2.28(s,3H),2.55-2.62(m,1H),3.99(d,J=8.5Hz,1H),4.14(d,J=8.4Hz,1H),4.30(d,J=9.3Hz,1H),4.83(t,J=17.6Hz,1H),4.97(d,J=9.6Hz,1H),5.58-5.61(m,2H),6.28(s,1H),7.47(t,J=15.5Hz,2H),7.60(t,J=15.6Hz,1H),8.09(d,J=7.7Hz,1H);13CNMR(125MHz,CDCl3)δ(ppm):10.73,13.89,14.16,15.18,20.12,20.77,21.02,22.25,22.51,24.14,26.57,31.15,34.11,38.58,42.75,47.39,56.15,60.42,71.33,74.44,75.84,76.32,76.81,166.90,168.90,170.64,173.12,202.52;
4n:1HNMR(500MHz,CDCl3)(ppm):3.84(s,3H),4.60(s,1H),4.65(d,J=1.0Hz,1H),5.75(d,J=9.5Hz,1H),7.13(d,J=9.0Hz,1H),7.3(t,J=14.4Hz,1H),7.38(t,J=15.6Hz,2H),7.45(t,J=16.0Hz,4H),7.77(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):45.33,53.27,54.98,73.25,126.91,127.60,128.00,128.77,133.93,138.57,141.16,166.44,173.38;
5n:1HNMR(500MHz,CDCl3)δ(ppm):3.80(s,3H),3.85(s,3H),5.01(s,1H),5.95(br,1H),6.90(d,J=8.5Hz,2H),7.13(br,1H),7.20-7.24(m,2H),7.30-7.39(m,4H),7.45(d,J=7.4Hz,2H),7.55(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):14.22,21.03,52.84,55.25,60.37,64.35,91.78,111.88,113.34,113.56,122.62,123.72,126.69,127.12,128.06,128.64,129.03,147.85,154.87,160.06,170.36;
6n:1HNMR(500MHz,CDCl3)δ(ppm):0.93(t,J=13.9Hz,3H),1.19(s,3H),1.26(s,3H),1.27-1.35(m,6H),1.57-1.63(m,2H),1.81(s,3H),1.89-1.94(m,2H),2.09(s,6H),2.19(s,3H),2.22-2.30(m,3H),2.34-2.41(m,1H),2.57-2.64(m,1H),3.85(s,3H),3.98(d,J=7.3Hz,1H),4.15(d,J=7.6Hz,1H),4.29(d,J=8.4Hz,1H),4.52(s,2H),4.92(d,J=9.3Hz,1H),5.63(t,J=17.3Hz,1H),5.68(d,J=16.2Hz,1H),6.33(s,2H),6.91(br,2H),7.23-7.30(m,5H),7.36(s,4H),7.47(t,J=15.5Hz,3H),7.61(t,J=15.6Hz,1H),8.05(d,J=8.6Hz,2H);13C-NMR(125MHz,CDCl3)δ(ppm):10.86,13.93,14.85,20.74,21.04,21.86,22.30,24.15,26.43,31.19,33.88,34.08,43.30,45.41,46.91,55.34,56.10,70.99,71.59,74.55,75.13,78.84,80.64,84.01,113.79,127.50,128.34,128.40,128.66,128.75,128.88,129.12,129.36,129.12,129.36,130.05,133.09,133.78,135.43,140.36,160.09,166.91,168.74,169.77,202.00;
7n:1H-NMR(CDCl3,500MHz)δppm:0.93(t,J=14.8Hz,3H),1.18(s,3H),1.20(s,3H),1.27(s,6H),1.58-1.65(m,3H),1.83(s,3H),1.84(s,3H),2.00(s,1H),2.05(s,2H),2.10(d,J=13.4Hz,1H),2.17(s,3H),2.24-2.27(m,1H),2.34(s,1H),2.39(s,3H),2.57-2.65(m,1H),3.83(t,J=18.6Hz,1H),3.93(d,J=6.8Hz,1H),3.98-4.027(m,1H),4.10-4.15(m,1H),4.20(d,J=8.4Hz,1H),4.33(d,J=8.5Hz,1H),4.59(s,1H),4.81(d,J=2.1Hz,1H),4.95(d,J=9.2Hz,1H),5.54-5.58(m,1H),5.69(d,J=6.8Hz,1H),5.80-5.82(m,1H),6.17(t,J=8.4Hz,1H),6.25(s,1H),7.28(d,J=6.9Hz,2H),7.35-7.37(m,2H),7.42(d,J=8.0Hz,3H),7.46-7.53(m,6H),7.60-7.64(m,1H),7.77(d,J=8.2Hz,2H),8.12(d,J=7.3Hz,2H).13C-NMR(CDCl3,125MHz)δppm:1.02,10.83,13.60,14.19,14.62,18.02,20.74,20.81,21.05,22.55,26.52,29.70,33.45,35.54,36.05,36.09,43.23,45.29,46.98,53.24,55.00,56.20,60.43,71.11,72.00,73.23,73.27,74.36,75.25,76.44,78.44,81.07,83.92,112.25,113.80,114.97,126.95,127.07,127.58,128.73,128.81,128.93,129.13,130.16,133.01,133.63,133.76,138.05,140.32,141.25,144.26,147.35,157.72,166.50,166.83,168.85,170.38,170.61,171.23,172.37,172.87,201.94.
HR-MS:calcdforC54H62ClNO15([M+H]+),1000.3886;found,1000.3874;
实施例十五：制备化合物3’-N-4-氯甲苯基-7-2-乙基己酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
2o：1HNMR(500MHz,CDCl3)δ(ppm):0.78-0.94(m,8H),1.04(s,3H),1.14(s,3H),1.18-1.31(m,3H),1.36-1.65(m,5H),2.13(s,3H),2.16(s,3H),2.28(s,3H),2.22-2.31(m,2H),2.56-2.64(m,1H),4.00(d,J=6.6Hz,1H),4.16(d,J=7.6Hz,1H),4.31(d,J=8.6Hz,1H),4.82(t,J=17.6Hz,1H),4.31(d,J=9.6Hz,1H),5.56(t,J=18.6Hz,1H),5.64(d,J=6.6Hz,1H),6.41(s,1H),7.47(t,J=15.5Hz,2H),7.60(t,J=15.4Hz,1H),8.10(d,J=9.5Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):10.81,11.08,11.36,13.90,14.16,15.02,20.11,20.78,22.51,22.60,23.67,23.92,26.52,28.85,28.99,29.70,30.32,33.41,38.51,42.68,45.98,46.03,47.29,56.55,60.44,67.65,71.19,71.22,74.49,75.89,76.37,78.61,80.49,83.85,128.62,129.35,130.08,131.56,133.65,145.10,166.93,168.81,170.70,175.02,202.52;
4o:1HNMR(500MHz,CDCl3)(ppm):3.84(s,3H),4.60(s,1H),4.65(d,J=1.0Hz,1H),5.75(d,J=9.5Hz,1H),7.13(d,J=9.0Hz,1H),7.3(t,J=14.4Hz,1H),7.38(t,J=15.6Hz,2H),7.45(t,J=16.0Hz,4H),7.77(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):45.33,53.27,54.98,73.25,126.91,127.60,128.00,128.77,133.93,138.57,141.16,166.44,173.38;
5o:1HNMR(500MHz,CDCl3)δ(ppm):3.80(s,3H),3.85(s,3H),5.01(s,1H),5.95(br,1H),6.90(d,J=8.5Hz,2H),7.13(br,1H),7.20-7.24(m,2H),7.30-7.39(m,4H),7.45(d,J=7.4Hz,2H),7.55(d,J=8.0Hz,2H);13CNMR(125MHz,CDCl3)δ(ppm):14.22,21.03,52.84,55.25,60.37,64.35,91.78,111.88,113.34,113.56,122.62,123.72,126.69,127.12,128.06,128.64,129.03,147.85,154.87,160.06,170.36;
6o:1HNMR(500MHz,CDCl3)δ(ppm):0.82-0.93(m,6H),1.22(s,3H),1.24(s,3H),1.27(s,3H),1.28-1.35(m,3H),1.40-1.72(m,6H),1.82(s,3H),1.89-1.94(m,2H),2.09(s,6H),2.15(s,3H),2.17(s,3H),2.27(d,J=6.3Hz,1H),2.58-2.66(m,1H),3.85(s,3H),4.00(d,J=6.3Hz,1H),4.16(d,J=8.6Hz,1H),4.30(d,J=9.4Hz,1H),4.52(s,2H),4.92(d,J=9.3Hz,1H),5.59(t,J=17.3Hz,1H),5.70(d,J=7.2Hz,1H),6.31(t,J=18.3Hz,1H),6.47(s,2H),6.91(Br,2H),7.23-7.30(m,5H),7.36(s,4H),7.48(t,J=15.5Hz,3H),7.61(t,J=15.6Hz,1H),8.05(d,J=8.6Hz,2H);13C-NMR(125MHz,CDCl3)δ(ppm):10.94,11.11,11.41,13.94,14.73,20.73,21.02,21.87,22.65,23.64,23.92,24.94,25.61,26.37,28.87,29.02,29.66,30.32,33.40,33.90,35.52,43.22,45.41,45.90,45.98,46.66,55.34,56.45,56.49,70.84,71.56,74.62,75.10,76.37,78.87,113.78,127.25,127.51,128.32,128.40,128.66,128.76,128.88,129.11,129.35,130.06,133.24,133.79,135.43,140.47,160.09,166.96,168.55,169.78,169.85,174.74,174.85,202.04;
7o:1HNMR(500MHz,CDCl3)δ(ppm):0.79-0.93(m,8H),1.19(s,3H),1.20(s,3H),1.41-1.65(m,6H),1.82(s,3H),1.81-1.90(m,2H),2.15(s,3H),2.24-2.35(m,4H),,2.39(s,3H),2.42-2.64(m,2H),3.69(s,1H),3.80(br,1H),3.93(d,J=8.3Hz,1H),4.21(d,J=9.2Hz,1H),4.32(d,J=7.6Hz,1H),4.60(s,2H),4.82(s,1H),4.93(d,J=9.1Hz,1H),5.51(t,J=16.3Hz,1H),5.70(d,J=6.5Hz,1H),5.81(d,J=10.6Hz,1H),6.17(t,J=7.5Hz,1H),6.38(s,1H),7.17(d,J=9.8Hz,1H),7.34-7.54(m,9H),7.63(t,J=15.5Hz,1H),7.77(d,J=7.7Hz,2H),8.13(d,J=8.3Hz,2H);13C-NMR(CDCl3,125MHz)δppm:1.02,10.91,11.07,11.38,13.93,14.13,14.52,14.53,18.39,20.71,20.72,20.80,22.18,22.57,22.64,22.70,23.61,23.84,26.48,27.64,28.85,29.00,29.63,29.70,30.25,30.78,33.50,35.54,43.17,45.29,45.88,45.96,46.74,51.71,53.44,54.87,56.55,56.58,62.05,68.53,70.92,70.96,72.12,73.18,74.43,75.17,75.19,76.51,78.48,80.02,83.81,127.06,127.55,128.32,128.73,128.84,128.98,129.12,130.18,133.22,133.62,133.78,138.00,140.32,141.31,166.43,166.90,168.61,170.34,172.36,174.89,174.98,201.94,201.96.
HR-MS:calcdforC56H66ClNO15([M+H]+),1028.4199;found,1028.4193;
实施例十六：制备化合物3’-N-4-正丙基苯基-7-正丁酰基巴卡亭III类似物的制备方法，该化合物的结构式为：
2p:1HNMR(500MHz,CDCl3)δ(ppm):0.83(t,J=13.3Hz,3H),1.11(s,3H),1.13(s,3H),1.27-1.33(m,4H),1.80(s,3H),1.87(br,1H),2.10(s,3H),2.13(s,3H),2.18-2.37(m,3H),2.26(s,3H),2.54-2.63(m,1H),3.95(d,J=8.3Hz,1H),4.13(d,J=8.3Hz,1H),4.29(d,J=9.5Hz,1H),4.83(t,J=17.6Hz,1H),5.00(d,J=9.4Hz,1H),5.58-5.61(m,2H),6.28(s,1H),7.45(t,J=15.4Hz,2H),7.56(t,J=15.4Hz,1H),8.06(d,J=7.5Hz,1H);13CNMR(125MHz,CDCl3)δ(ppm):1.02,10.75,13.60,15.19,18.03,20.06,20.80,22.58,26.64,29.69,33.44,36.08,38.43,42.80,47.39,56.26,67.93,71.26,74.40,75.84,76.37,77.22,78.63,80.69,84.03,128.64,129.30,130.10,131.68,133.09,144.58,167.02,168.85,170.66,172.82,202.46;
4p:1HNMR(CDCl3,500MHz)δ(ppm):0.95(t,J=15.5Hz,3H),1.61-1.68(m,2H),2.61(t,J=15.3Hz,2H),3.76(s,3H),4.10(d,J=4.3Hz,1H),4.60(s,1H),5.74(dd,J=2.3Hz,J=2.2Hz,1H),7.17(d,J=8.4Hz,2H),7.26-7.34(m,4H),7.43(d,J=7.2Hz,2H),7.69(d,J=8.3Hz,2H);13C-NMR(125MHz,CDCl3)δ(ppm):13.75,24.32,37.87,52.98,55.10,73.43,126.97,127.23,127.75,128.61,128.64,131.38,138.86,146.89,167.21,173.32;
5p:1HNMR(CDCl3,500MHz)δ(ppm):0.91(t,J=15.5Hz,3H),1.57-1.65(m,2H),2.56(t,J=15.3Hz,2H),3.82(s,3H),3.83(s,3H),4.89(br,1H),6.86(br,1H),7.05(d,J=8.8Hz,2H),7.25(d,J=9.7Hz,3H),7.32(br,4H);13C-NMR(125MHz,CDCl3)δ(ppm):13.68,24.21,37.80,52.72,55.25,113.48,127.08,127.15,128.00,128.31,128.64,128.75,132.97,159.89,170.54;
6p:1HNMR(500MHz,CDCl3)δ(ppm):0.86-0.95(m,6H),1.18(s,3H),1.24(s,3H),1.27(s,3H),1.54-1.66(m,4H),1.80(s,3H),2.09(s,6H),2.19(s,3H),2.21-2.29(m,3H),2.32-2.40(m,1H),2.53(t,J=16.3Hz,1H),2.56-2.64(m,1H),3.83(s,3H),3.98(d,J=7.3Hz,1H),4.14(d,J=9.6Hz,1H),4.27(d,J=9.4Hz,1H),4.91(d,J=10.1Hz,1H),5.62(t,J=17.3Hz,1H),5.68(d,J=7.2Hz,1H),6.32(s,1H),6.90(Br,2H),7.03(d,J=9.1Hz,1H),7.22(d,J=7.1Hz,1H),7.34(s,3H),7.45(t,J=15.5Hz,3H),7.61(t,J=15.6Hz,1H),8.04(d,J=8.6Hz,2H);13C-NMR(125MHz,CDCl3)δ(ppm):10.86,13.62,13.67,14.84,18.00,20.74,21.05,21.83,24.19,26.40,33.34,35.57,36.03,37.77,43.28,46.89,55.30,56.08,71.02,71.58,74.58,75.15,76.29,78.77,80.60,84.01,113.70,127.21,128.19,128.30,128.64,128.72,128.78,129.16,129.67,130.04,132.72,133.04,133.75,140.44,160.00,166.84,168.77,169.81,170.01,172.69,202.04;
7p:1H-NMR(CDCl3,500MHz)δppm:0.89-0.94(m,6H),1.17(s,3H),1.18(s,3H),1.25(d,J=14.6Hz,3H),1.56-1.68(m,6H),1.81(s,3H),1.89(s,3H),1.84(s,3H),2.16(s,3H),2.21-2.36(m,6H),2.60(t,J=16.6Hz,3H),3.91(d,J=7.6Hz,3H),4.20(d,J=9.3Hz,1H),4.30(d,J=7.7Hz,1H),4.80(s,1H),4.94(d,J=9.3Hz,1H),5.28(s,1H),5.55(t,J=16.6Hz,1H),5.68(d,J=6.6Hz,1H),5.83(d,J=10.2Hz,1H),6.16(t,J=7.7Hz,1H),6.25(s,1H),7.18(d,J=9.2Hz,1H),7.25-7.34(m,2H),7.39(t,J=16.7Hz,1H),7.46-7.52(m,4H),7.61(t,J=15Hz,1H),7.67(d,J=8.6Hz,2H),8.13(d,J=7.3Hz,2H);13C-NMR(CDCl3,125MHz)δppm:10.82,13.59,13.72,14.18,14.58,18.00,20.73,20.86,21.02,22.52,24.26,26.48,36.04,37.84,43.23,46.94,52.87,54.99,56.16,60.43,71.11,71.96,73.31,74.38,75.26,78.36,81.01,83.93,127.07,127.12,128.14,128.69,128.73,128.87,129.19,130.16,132.93,133.70,138.24,147.11,166.67,167.22,168.85,170.35,17247,172.84,201.98.
HR-MS:calcdforC54H63NO15([M+H]+),966.4276;found,966.4264;
实施例十七：抗炎生物活性体外筛选试验
实验前一天按1x105个/孔接种到48孔板中，细胞培养箱中培养RAW264.7。取出已用DMSO稀释好的系列化合物以及紫杉醇药物，加到新换的无血清培养基中，使其使用浓度为10μmol/L。药物，DMSO以及LPS对细胞进行处理，收集孔板中的培养上清ELISA检测（TNF-α），分析结果，参见图1，（请给出分析结果）。

Claims (2)

1.一种C-13和C-7位结构改造的紫杉醇类化合物，其特征在于紫杉醇类化合物的结构式为：
；
其中R1为：正丁羰基、正己羰基、-噻吩羰基、-溴正戊基羰基、-甲苯基羰基、-乙基正己羰基；R2为：-呋喃羰基、-噻吩羰基、-氯甲基苯基羰基、-正丙基苯基羰基。
2.一种制备根据权利要求1所述的C-13和C-7位结构改造的紫杉醇类化合物的方法，其特征在于该方法的具体步骤为：
a．将紫杉醇、三乙胺、酰氯和二甲氨基吡啶（DMAP）按1:3:1.2:1的摩尔比溶于甲苯中，在50~55oC下，搅拌反应至反应结束；用乙酸乙酯萃取，饱和食盐水洗涤，无水硫酸钠干燥，减压蒸除溶剂，初产物经分离提纯得白色固体7-酰基巴卡亭III，其结构为：；所述的酰氯的结构式为：、、、、、；
b.惰性气氛保护下，冰水浴下，将苯异丝氨酸和二氯亚砜按1:2.5的摩尔比溶于无水甲醇中，过夜反应；蒸出溶剂，乙酸乙酯和水萃取，取有机相干燥后旋干，经分离提纯，得甲酯化中间体；冰水浴下，将该甲酯化中间体和酰氯按1:3的摩尔比溶于四氢呋喃和饱和碳酸氢钠溶液混合溶液中，室温下搅拌反应至反应结束，蒸除四氢呋喃，经乙酸乙酯萃取、干燥后，蒸除溶剂，得粗产物；该粗产物经分离提纯得产物3-酰胺苯异丝氨酸甲酯，其结构式为：；所述的酰氯的结构式为：、、、；
c.在惰性气体保护下，将步骤b所得化合物3-酰胺苯异丝氨酸甲酯和4-甲氧基苯甲醛二甲基缩醛按1：1.5的摩尔比溶于重蒸的甲苯中，加入催化量的对甲苯磺酸吡啶盐，110oC下搅拌两个小时，乙酸乙酯萃取，无水硫酸钠干燥，减压蒸除溶剂；粗产物经分离提纯得黄色油状液体(4S,5R)-3-酰基-2-(4-甲氧基苯基)-4-苯基-5-恶唑啉羧酸甲酯，其结构式为：；
d.将步骤c所得化合物(4S,5R)-3-酰基-2-(4-甲氧基苯基)-4-苯基-5-恶唑啉羧酸甲酯溶于无水甲醇中，加入NaOH溶液水解，其中(4S,5R)-3-酰基-2-(4-甲氧基苯基)-4-苯基-5-恶唑啉羧酸甲酯与NaOH的摩尔比为1：1.2室温下搅拌2h；反应结束后，减压蒸除溶剂，无水乙醚萃取；调节水相pH为2，出现饱和羧酸白色固体，水相用乙酸乙酯萃取3次，合并有机相，有机相用饱和食盐水洗3次，无水Na2SO4干燥；除去溶剂得中间产物，将该中间产物、二环己基碳二亚胺（DCC）和二甲氨基吡啶（DMAP）按1:2:3:1的摩尔比溶于甲苯中，40℃反应至反应结束；用乙酸乙酯萃取，再用饱和NaCl溶液洗涤，有机相用Na2SO4干燥，除去溶剂，初产物经分离提纯,得白色固体产物7-取代-13-(4S,5R)-3ˊ-酰基-2ˊ-(4-甲氧基苯基)-4ˊ-苯基-5ˊ-恶唑啉紫杉醇，其结构式为：
；
e.将化合物7-取代-13-(4S,5R)-3ˊ-酰基-2ˊ-(4-甲氧基苯基)-4ˊ-苯基-5ˊ-恶唑啉紫杉醇和对苯甲磺酸按1:0.5的摩尔比溶于无水甲醇中，室温下反应至反应结束，混合液用乙酸乙酯稀释，分别用饱和碳酸氢钠和饱和食盐水洗涤，无水Na2SO4干燥，除去溶剂，粗产物经分离提纯得白色固体C-13和C-7位结构改造的紫杉醇类化合物。
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