CN111269205B - 一种c-芳基糖苷化合物的制备方法 - Google Patents

一种c-芳基糖苷化合物的制备方法 Download PDF

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CN111269205B
CN111269205B CN202010101661.9A CN202010101661A CN111269205B CN 111269205 B CN111269205 B CN 111269205B CN 202010101661 A CN202010101661 A CN 202010101661A CN 111269205 B CN111269205 B CN 111269205B
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程国林
吕薇薇
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Huaqiao University
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    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
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Abstract

本发明公开了一种C‑芳基糖苷化合物的制备方法，包括如下步骤：(1)向经氮气吹扫的反应容器中依次加入碱、助催化剂、钯催化剂、配体、卤代芳烃、糖基氯化物、终止试剂和有机溶剂，于80～120℃反应15～30h，得到混合物料；(2)将步骤(1)所得的混合物料经乙酸乙酯稀释后，再经水洗，分离得有机相；(3)将步骤(2)所得的有机相经干燥、过滤、浓缩、薄层色谱或柱层析色谱，得到所述C‑芳基糖苷化合物。本发明可以得到不同芳基取代的C‑芳基糖苷化合物，步骤简单操作安全，并且有良好的立体选择性，能够合成其他方法不易得到的具有C‑芳基糖苷化合物。

Description

一种C-芳基糖苷化合物的制备方法
技术领域
本发明属于有机合成技术领域，具体涉及一种C-芳基糖苷化合物的制备方法。
背景技术
酶催化的糖苷化是自然界修饰生物活性分子的重要手段，除了常见的O-糖苷和N-糖苷以外，C-芳基糖苷类化合物也广泛存在于自然界并在药物设计中有着重要的作用，许多带有芳基糖苷的化合物都表现出优异的生物活性，例如抗真菌和抗肿瘤作用。由于C-糖苷键的高度稳定性，碳苷化也是含糖缀药物改造的有效策略。在抗癌药(噻唑呋林)和抗糖尿病药(达格列净、卡格列净和依帕列净)中发现的C-芳基吡喃糖和呋喃糖键已被证明在药物设计中是极好的仿糖药效团。传统构建芳基糖苷方法有：一是通过当量Lewis酸催化富电子芳烃与糖基给体发生傅-克类型的糖基化反应；二是利用预官能团化的芳基金属试剂与糖基给体进行偶联构筑C-糖苷键。这些方法往往存在着区域选择性和立体选择性差、芳基金属物种预官能团化操作繁琐等局限。因此，发展高效、高立体选择性的芳基糖苷的合成方法在糖化学领域和医药研发领域受到越来越多的重视。
发明内容
本发明的目的在于克服现有技术的不足之处，提供了一种C-芳基糖苷化合物的制备方法，解决了上述背景技术中的问题。
本发明解决其技术问题所采用的技术方案是：提供了一种C-芳基糖苷化合物的制备方法，包括如下步骤：
(1)向经氮气吹扫的反应容器中依次加入碱、助催化剂、钯催化剂、配体、卤代芳烃、糖基氯化物、终止试剂和有机溶剂，于80～120℃反应15～30h，得到混合物料；
其中，所述碱、助催化剂、钯催化剂、配体、卤代芳烃、糖基氯化物和终止试剂的摩尔比为1.8～3.5:1.0～2.5:0.08～0.12:0.18～0.22:0.8～1.2:1.0～2.0:1.0～2.5，且每摩尔卤代芳烃对应的有机溶剂为1～3L；
(2)将步骤(1)所得的混合物料经乙酸乙酯稀释后，再经水洗，分离得有机相；
(3)将步骤(2)所得的有机相经干燥、过滤、浓缩、薄层色谱或柱层析色谱，得到所述C-芳基糖苷化合物。
在本发明一较佳实施例中，一种C-芳基糖苷化合物的制备方法的反应路线如下：
Figure BDA0002387057500000021
在本发明一较佳实施例中，所述碱为氢氧化钠、氢氧化钾、叔丁醇锂、叔丁醇钠、叔丁醇钾、甲醇钠、乙醇钠、碳酸钠、磷酸钠、碳酸钾、磷酸钾、磷酸二氢钾、碳酸铯、醋酸铯、氢氧化铯或1,8-二氮杂二环十一碳-7-烯。
在本发明一较佳实施例中，所述助催化剂的结构式为
Figure BDA0002387057500000022
其中R3为氢、烷基、酰基、芳基、羧酸基、酯基、酰胺基、磺酰基或三氟甲基，R4为氢、烷基、芳基、酰基、羧酸基、酯基、酰胺基、磺酰基或三氟甲基。
在本发明一较佳实施例中，所述钯催化剂为醋酸钯、三氟醋酸钯、二氯化钯、双三苯基膦基二氯化钯、双乙腈二氯化钯、乙酰丙酮钯、二乙酰丙酮钯、烯丙基氯化钯二聚物、四三苯基膦钯、[1,1'-双(二苯基膦)二茂铁]二氯化钯或三(二亚苄基丙酮)二钯。
在本发明一较佳实施例中，所述配体为三苯基膦、三(2-呋喃基)膦、2-二环己基磷-2',6'-二异丙氧基-1,1'-联苯、三萘基膦、2-二环己基磷-2,4,6-三异丙基联苯、2-双环己基膦-2',6'-二甲氧基联苯、三环己基膦、4,5-双二苯基膦-9,9-二甲基氧杂蒽、三(2-甲氧基苯基)膦、三(4-甲氧基苯基)膦、吡啶、联吡啶、2-羟基-3-三氟甲基吡啶，1,1'-联萘-2,2'-双二苯膦、1,1'-双(二苯基膦)二茂铁或1,1'-联-2-萘酚。
在本发明一较佳实施例中，所述卤代芳烃的结构式为
Figure BDA0002387057500000031
其中X为卤素，R为氢、烷基、烷氧基、酰基、羧酸酯基、酰胺基、三氟代烷基、三氟代烷氧基、芳基、取代芳基、羟基、羟甲基、卤素、杂环或甾体。
在本发明一较佳实施例中，所述糖基氯化物的结构式为
Figure BDA0002387057500000032
或者
Figure BDA0002387057500000033
其中R1为烷基或硅基。/>
在本发明一较佳实施例中，所述上述终止试剂的结构式为
Figure BDA0002387057500000034
其中R2为酰基、芳基、羧酸酯基基和酰胺基，Tips为三异丙基硅基。
在本发明一较佳实施例中，所述有机溶剂为二甲基亚砜、N，N－二甲基甲酰胺、N，N－二甲基乙酰胺、N-甲基-2-吡咯烷酮、六氟异丙醇、1,2-二氯乙烷、甲苯、1,4-二氧六环、乙腈、四氢呋喃、乙二醇二甲醚、甲基叔丁基醚、聚乙二醇二甲醚和乙二醇二乙醚。
在本发明一较佳实施例中，所述步骤(1)中，向经氮气吹扫的反应容器中依次加入碱、助催化剂、钯催化剂、配体、卤代芳烃、糖基氯化物、终止试剂和有机溶剂，于90～110℃反应24h，得到混合物料；
其中，所述碱、助催化剂、钯催化剂、配体、卤代芳烃、糖基氯化物和终止试剂的摩尔比为3:2:0.1:0.2:1:1.5:2，且每摩尔卤代芳烃对应的有机溶剂为1～2L。
在本发明一较佳实施例中，所述R为卤素、甲基、三氟甲基、甲氧基、羧酸酯基和酰胺基，其中，所述卤素为氟、碘、氯或溴。
在本发明一较佳实施例中，所述钯催化剂为醋酸钯，所述配体为三(2-呋喃基)膦，所述碱为碳酸铯、碳酸钾，所述有机溶剂为四氢呋喃、乙腈。
本技术方案与背景技术相比，它具有如下优点：
1、本发明可以同时得到不同芳基取代的C-芳基糖苷化合物，并且有良好的立体选择性，能够合成其他方法不易得到的芳基糖苷；
2、本发明的方法收率高，反应条件温和操作步骤简单，底物范围广，后处理简便且绿色。
具体实施方式
实施例1
methyl
(E)-3-(2-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)naphthalen-1-yl)acrylate的制备
Figure BDA0002387057500000041
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，1-碘萘0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到71.9mg目标产物，收率为98％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.37(d,J＝16.2Hz,1H),8.08–8.00(m,1H),7.92–7.83(m,2H),7.78(d,J＝8.7Hz,1H),7.60–7.51(m,2H),7.46–7.24(m,19H),7.21–7.15(m,1H),7.12-7.09(m,2H),6.90-6.89(m,2H),6.52(d,J＝16.2Hz,1H),5.54(d,J＝9.4Hz,1H),4.80(d,J＝12.2Hz,1H),4.66–4.56(m,2H),4.58–4.45(m,3H),4.33(t,J＝6.9Hz,1H),4.18–4.05(m,3H),4.01(t,J＝3.3Hz,1H),3.95(dd,J＝9.9,6.9Hz,1H),3.91–3.82(m,2H),3.77(s,3H)；13C NMR(126MHz,CDCl3)δ166.8,142.3,138.5,138.3,138.1,137.8,135.1,132.9,132.6,131.2,128.8,128.4,128.2,128.2,128.0,127.7,127.6,127.5,127.5,127.4,127.4,127.3,126.5,126.4,126.0,125.3,124.7,77.7,75.4,75.1,74.9,73.1,71.8,71.6,68.3,68.2,51.5.
实施例2
methyl
(E)-3-(2-methyl-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000051
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2-甲基碘苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到59.3mg目标产物，收率为85％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.93(d,J＝16.3Hz,1H),7.42(d,J＝7.8Hz,1H),7.38–7.20(m,19H),7.18(d,J＝7.5Hz,1H),7.00(dd,J＝6.7,2.9Hz,2H),6.26(d,J＝16.3Hz,1H),5.31(d,J＝8.8Hz,1H),4.72(d,J＝12.2Hz,1H),4.63–4.54(m,2H),4.55–4.42(m,3H),4.25–4.10(m,3H),3.99(dd,J＝8.8,2.6Hz,1H),3.95(t,J＝3.4Hz,1H),3.90–3.78(m,3H),3.70(s,3H),2.33(s,3H)；13C NMR(126MHz,CDCl3)δ166.9,143.4,138.5,138.4,138.1,138.1,137.7,136.0,135.2,129.6,128.4,128.2,128.2,128.1,127.7,127.6,127.6,127.5,127.5,127.4,127.4,127.3,125.2,124.8,78.1,75.2,75.2,75.1,73.1,73.0,71.8,71.8,68.4,68.4,51.4,20.9.
实施例3
methyl
(E)-3-(2-methoxy-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000061
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2-甲氧基碘苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到44.2mg目标产物，收率为62％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.08(d,J＝16.2Hz,1H),7.46–7.27(m,17H),7.26–7.22(m,3H),7.10–7.01(m,2H),6.91(dd,J＝8.3,1.1Hz,1H),6.71(d,J＝16.3Hz,1H),5.43(d,J＝8.8Hz,1H),4.77(d,J＝12.3Hz,1H),4.64–4.60(m,2H),4.57–4.45(m,3H),4.26–4.18(m,3H),4.01(dd,J＝8.8,2.6Hz,1H),3.98–3.96(m,1H),3.95–3.83(m,6H),3.72(s,3H)；13C NMR(126MHz,CDCl3)δ167.7,158.0,140.2,139.2,138.5,138.4,138.2,138.1,129.7,128.4,128.2,128.1,127.7,127.6,127.6,127.5,127.4,127.4,127.3,124.2,123.7,120.0,110.0,78.1,75.3,75.3,75.1,73.1,73.1,71.8,71.8,68.3,68.2,55.6,51.3.
实施例4
methyl
(E)-3-(2-fluoro-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000071
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2-氟碘苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到43.5mg目标产物，收率为62％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.98(d,J＝16.3Hz,1H),7.41–7.21(m,18H),7.22–7.17(m,2H),7.06–7.03(m,1H),7.01–6.93(m,2H),6.54(d,J＝16.3Hz,1H),5.27(d,J＝8.6Hz,1H),4.70(d,J＝12.1Hz,1H),4.64–4.53(m,2H),4.47(d,J＝12.9Hz,3H),4.25–4.14(m,2H),4.10(d,J＝11.9Hz,1H),3.92–3.88(m,3H),3.82–3.81(m,1H),3.77–3.74(m,1H),3.69(s,3H)；13C NMR(126MHz,CDCl3)δ167.2,161.0(d,J＝251.6Hz),141.3,138.3(d,J＝4.0Hz),138.1,137.8,136.4,130.0(d,J＝8.7Hz),128.4,128.3,128.3,128.1,127.7,127.7,127.6,127.6,127.5,127.5,127.4,126.9,124.5(d,J＝11.3Hz),123.6(d,J＝3.0Hz),122.8,122.7,115.2(d,J＝23.0Hz),77.8,75.4,74.9,74.6,73.1,73.1,71.8,71.6,68.3,68.0,51.5.
实施例5
methyl
(E)-3-(2-chloro-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000081
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2-氯碘苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到34.5mg目标产物，收率为48％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.89(d,J＝16.3Hz,1H),7.52(dd,J＝7.9,1.2Hz,1H),7.43–7.31(m,4H),7.34–7.18(m,16H),6.95(dd,J＝7.2,2.3Hz,2H),6.48(d,J＝16.3Hz,1H),5.30(d,J＝9.0Hz,1H),4.71(d,J＝12.2Hz,1H),4.61–4.52(m,2H),4.49–4.43(m,3H),4.27–4.16(m,2H),4.09(d,J＝12.0Hz,1H),3.95–3.91(m,2H),3.86–3.83(m,1H),3.83-3.81(m,1H),3.77–3.75(m,1H),3.70(s,3H)；13C NMR(126MHz,CDCl3)δ166.6,140.7,140.4,138.4,138.3,138.0,137.7,134.2,133.4,129.2,128.9,128.4,128.3,128.2,127.7,127.7,127.6,127.5,127.5,127.5,126.3,126.2,78.2,75.5,75.0,74.6,73.1,73.1,71.7,68.1,67.9,51.6.
实施例6
methyl
(E)-3-(2,3-dimethyl-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000091
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，3-碘邻二甲苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到42.7mg目标产物，收率为60％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.97(d,J＝16.3Hz,1H),7.39–7.20(m,19H),7.13(d,J＝8.0Hz,1H),7.07–7.02(m,2H),6.17(d,J＝16.3Hz,1H),5.24(d,J＝8.5Hz,1H),4.72(d,J＝12.2Hz,1H),4.63–4.55(m,2H),4.54–4.49(m,2H),4.45(d,J＝12.0Hz,1H),4.25(d,J＝12.0Hz,1H),4.19(d,J＝12.1Hz,1H),4.15–4.12(m,1H),4.00(dd,J＝8.5,2.7Hz,1H),3.94-3.94(m,1H),3.87–3.82(m,3H),3.70(s,3H),3.32(s,3H),3.22(s,3H)；13C NMR(126MHz,CDCl3)δ166.9,144.6,138.6,138.5,138.2,136.3,135.6,135.1,134.1,129.7,128.4,128.2(d,J＝1.9Hz),128.1,127.7,127.6,127.5,127.5,127.4,127.4,127.3,124.8,124.7,77.9,75.6,75.2,75.1,73.2,73.0,71.9,71.9,68.9,68.6,51.4,20.4,16.9.
实施例7
methyl
(E)-3-(3-fluoro-2-methyl-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000101
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2-氟-6-碘-甲苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到53.7mg目标产物，收率为75％。该化合物的核磁表征如下：1HNMR(500MHz,CDCl3)δ7.87(d,J＝16.3Hz,1H),7.40–7.19(m,19H),7.04–6.94(m,3H),6.23(d,J＝16.3Hz,1H),5.22(d,J＝8.8Hz,1H),4.71(d,J＝12.2Hz,1H),4.65–4.55(m,2H),4.53–4.43(m,3H),4.26–4.17(m,2H),4.12(d,J＝12.0Hz,1H),3.98–3.90(m,2H),3.90–3.75(m,3H),3.71(s,3H),2.23(s,3H)；13C NMR(126MHz,CDCl3)δ166.6,160.4(d,J＝244.3Hz),142.3,142.2,138.5,138.3,138.1,137.9,137.4(d,J＝4.6Hz),133.5(d,J＝3.0Hz),128.4,128.3,128.2,128.1,127.7,127.7,127.6,127.5,127.5,127.4,127.4,126.4(d,J＝8.9Hz),125.7,122.7(d,J＝16.3Hz),114.8(d,J＝23.1Hz),78.0,75.3,75.0,74.8,73.1,73.0,71.7,71.7,68.3,68.0,51.5,12.0(d,J＝5.4Hz).
实施例8
methyl
(E)-3-(3-chloro-2-methyl-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000111
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2-氯-6-碘甲苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到49.7mg目标产物，收率为67％。该化合物的核磁表征如下：1HNMR(500MHz,CDCl3)δ7.86(d,J＝16.3Hz,1H),7.40–7.19(m,20H),7.00–6.96(m,2H),6.19(d,J＝16.3Hz,1H),5.20(d,J＝8.9Hz,1H),4.71(d,J＝12.2Hz,1H),4.61-4.54(m,2H),4.53–4.42(m,3H),4.24(d,J＝12.0Hz,1H),4.22–4.18(m,1H),4.12(d,J＝12.0Hz,1H),3.95–3.89(m,2H),3.87–3.75(m,3H),3.70(s,3H),2.36(s,3H)；13C NMR(126MHz,CDCl3)δ166.5,143.1,138.5,138.3,138.1,137.8,137.3,136.5,134.2,133.4,128.9,128.4,128.3,128.2,128.1,127.7,127.7,127.6,127.5,127.5,127.4,126.1,125.8,78.0,75.3,75.0,74.7,73.2,73.0,71.7,71.7,68.3,68.1,51.5,17.7.
实施例9
methyl
3-((E)-3-methoxy-3-oxoprop-1-en-1-yl)-2-methyl-4-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)benzoate的制备
Figure BDA0002387057500000121
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，3-碘-2-甲基苯甲酸甲酯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到54.5mg目标产物，收率为72％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.87(d,J＝16.3Hz,1H),7.76(d,J＝8.2Hz,1H),7.48(d,J＝8.3Hz,1H),7.39–7.18(m,19H),6.95(dd,J＝7.4,2.1Hz,2H),6.18(d,J＝16.3Hz,1H),5.26(d,J＝8.8Hz,1H),4.73–4.67(m,1H),4.61–4.39(m,5H),4.24–4.18(m,2H),4.08(d,J＝12.0Hz,1H),3.96–3.89(m,5H),3.88–3.74(m,3H),3.69(s,3H),2.49(s,3H)；13C NMR(126MHz,CDCl3)δ168.4,166.5,143.4,141.3,138.4,138.3,138.0,137.8,137.0,136.9,130.4,129.7,128.5,128.4,128.3,128.2,128.1,127.7,127.7,127.6,127.5,127.5,127.5,126.9,125.8,124.8,78.2,75.4,75.0,74.7,73.2,73.0,71.8,71.7,68.2,52.0,51.5,18.3.
实施例10
methyl
(E)-3-(2,4-dimethyl-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000131
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，4-碘间二甲苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到57.7mg目标产物，收率为81％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.94(d,J＝16.2Hz,1H),7.41–7.32(m,4H),7.33–7.27(m,11H),7.28–7.19(m,4H),7.01-7.00(m,3H),6.29(d,J＝16.2Hz,1H),5.32(d,J＝8.6Hz,1H),4.74(d,J＝12.3Hz,1H),4.66–4.56(m,2H),4.52(d,J＝11.8Hz,2H),4.46(d,J＝12.1Hz,1H),4.27–4.19(m,2H),4.15(d,J＝12.1Hz,1H),4.01–3.94(m,2H),3.90–3.80(m,3H),3.70(s,3H),2.32(s,6H)；13C NMR(126MHz,CDCl3)δ167.1,143.4,138.6,138.4,138.1,138.1,138.0,137.7,136.0,132.3,130.6,128.4,128.2,128.0,127.7,127.7,127.6,127.5,127.5,127.4,127.3,125.7,124.3,75.2,75.2,75.0,73.1,72.9,71.8,71.6,68.4,68.3,51.4,21.2,20.9.
实施例11
methyl
(E)-3-(4-fluoro-2-methyl-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000141
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，4-氟-1-碘-2-甲苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到60.1mg目标产物，收率为84％。该化合物的核磁表征如下：1HNMR(500MHz,CDCl3)δ7.85(d,J＝16.3Hz,1H),7.40–7.22(m,18H),7.18(dd,J＝9.9,2.7Hz,1H),7.01–6.97(m,2H),6.91(dd,J＝9.0,2.6Hz,1H),6.29(d,J＝16.2Hz,1H),5.30(d,J＝9.1Hz,1H),4.73(d,J＝12.2Hz,1H),4.63–4.52(m,2H),4.55–4.42(m,3H),4.26–4.23(m,2H),4.11(d,J＝12.0Hz,1H),3.96(t,J＝3.2Hz,1H),3.94–3.84(m,2H),3.83(dd,J＝3.9,1.4Hz,1H),3.78(dd,J＝9.9,6.7Hz,1H),3.70(s,3H),2.34(s,3H)；13C NMR(126MHz,CDCl3)δ166.8,162.4(d,J＝247.3Hz),142.4,140.7(d,J＝7.6Hz),138.7(d,J＝8.0Hz),138.4,138.3,138.0,137.8,131.1(d,J＝3.0Hz),128.4,128.2,128.1,127.7,127.7,127.6,127.5,127.5,127.4,127.4,125.1,116.5(d,J＝21.3Hz),112.0(d,J＝22.2Hz),78.3,75.4,75.0,74.7,73.1,73.1,71.7,71.7,68.2,67.8,51.4,21.0.
实施例12
methyl
(E)-3-(4-chloro-2-methyl-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000151
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，4-氯-1-碘-2-甲苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到65.9mg目标产物，收率为90％。该化合物的核磁表征如下：1HNMR(500MHz,CDCl3)δ7.82(d,J＝16.2Hz,1H),7.45(d,J＝2.1Hz,1H),7.41–7.19(m,18H),7.17(d,J＝2.1Hz,1H),6.97(dd,J＝7.1,2.5Hz,2H),6.28(d,J＝16.2Hz,1H),5.25(d,J＝9.2Hz,1H),4.70(d,J＝12.2Hz,1H),4.62–4.54(M,2H),4.52–4.41(m,3H),4.29–4.20(m,2H),4.09(d,J＝12.0Hz,1H),3.94(t,J＝3.2Hz,1H),3.92–3.83(m,2H),3.81(dd,J＝3.9,1.5Hz,1H),3.75(dd,J＝10.0,6.7Hz,1H),3.69(s,3H),2.30(s,3H)；13C NMR(126MHz,CDCl3)δ166.7,142.2,139.9,138.4,138.3,138.0,137.9,137.9,137.9,137.7,134.1,133.6,129.5,128.4,128.3,128.1,127.7,127.7,127.6,127.5,127.4,125.4,125.3,78.0,75.4,74.9,74.6,73.1,73.0,71.7,71.6,68.1,67.7,51.5,20.8.
实施例13
methyl
4-((E)-3-methoxy-3-oxoprop-1-en-1-yl)-3-methyl-5-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)benzoate的制备
Figure BDA0002387057500000161
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，4-碘-2-甲基苯甲酸甲酯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到62mg目标产物，收率为82％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.12(d,J＝1.6Hz,1H),7.89–7.83(m,2H),7.39–7.34(m,3H),7.34–7.21(m,15H),7.21–7.14(m,3H),6.92(dd,J＝7.5,1.9Hz,2H),6.25(d,J＝16.3Hz,1H),5.28(d,J＝9.3Hz,1H),4.69(d,J＝12.1Hz,1H),4.62(d,J＝12.3Hz,1H),4.54(d,J＝12.2Hz,1H),4.52–4.46(m,2H),4.43(d,J＝12.1Hz,1H),4.23(dd,J＝12.8,5.7Hz,2H),4.05(d,J＝11.9Hz,1H),4.00(dd,J＝9.3,2.6Hz,1H),3.96(t,J＝3.3Hz,1H),3.92(s,3H),3.88–3.81(m,2H),3.78(dd,J＝9.9,6.8Hz,1H),3.68(s,3H),2.35(s,3H)；13C NMR(126MHz,CDCl3)δ166.8,166.6,142.5,139.9,138.5,138.4,138.3,138.1,137.8,136.3,130.4,129.7,128.5,128.4,128.3,128.1,127.7,127.6,127.5,127.5,127.4,127.4,126.9,126.4,125.8,78.1,75.2,74.9,74.8,73.1,73.0,71.7,71.6,68.2,68.0,52.0,51.5,20.8.
实施例14
methyl
(E)-3-(4-(methoxy(methyl)carbamoyl)-2-methyl-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000171
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，4-碘-N-甲氧基-N，3-二甲基苯甲酰胺0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到70.7mg目标产物，收率为90％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.89(d,J＝16.3Hz,1H),7.84–7.80(m,1H),7.53–7.49(m,1H),7.38–7.19(m,18H),7.01-6.98(dt,J＝7.3,3.8Hz,2H),6.26(d,J＝16.3Hz,1H),5.30(d,J＝9.1Hz,1H),4.71(d,J＝12.1Hz,1H),4.56(dd,J＝16.3,12.2Hz,2H),4.52–4.42(m,3H),4.21(dd,J＝9.6,5.7Hz,2H),4.10(d,J＝11.9Hz,1H),3.99(dd,J＝9.1,2.7Hz,1H),3.93(t,J＝3.3Hz,1H),3.87(dd,J＝10.0,6.9Hz,1H),3.84–3.75(m,2H),3.69(s,3H),3.52(s,3H),3.34(s,3H),2.35(s,3H)；13C NMR(126MHz,CDCl3)δ169.6,166.7,142.6,138.4,138.3,138.1,137.9,137.9,137.8,137.5,136.0,136.0,133.7,129.2,128.3,128.2,128.1,127.6,127.5,127.4,127.4,125.5,125.2,78.3,75.2,75.0,75.0,73.1,73.0,71.9,71.6,68.3,68.2,61.0,51.5,33.9,20.9.
实施例15
methyl
(E)-3-(2-fluoro-4-methyl-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000181
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2-氟-1-碘-4-甲苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到45.8mg目标产物，收率为63％。该化合物的核磁表征如下：1HNMR(500MHz,CDCl3)δ8.00(d,J＝16.2Hz,1H),7.41–7.24(m,15H),7.25–7.20(M,3H),7.20–7.15(m,1H),7.04–6.98(m,2H),6.89(d,J＝11.9Hz,1H),6.57(d,J＝16.3Hz,1H),5.30(d,J＝9.0Hz,1H),4.75(d,J＝12.3Hz,1H),4.62(dd,J＝23.5,12.2Hz,2H),4.55–4.48(m,3H),4.28–4.16(m,2H),4.12(d,J＝12.0Hz,1H),3.98–3.88(m,3H),3.85(dd,J＝4.2,1.8Hz,1H),3.80(dd,J＝10.0,6.4Hz,1H),3.71(s,3H),2.34(s,3H)；13C NMR(126MHz,CDCl3)δ167.4,161.1(d,J＝251.5Hz),141.0(d,J＝9.5Hz),140.9,138.4,138.3,138.1,137.8,136.5,128.4,128.3,128.3,128.1,127.7,127.6,127.6,127.5,127.5,127.4,124.2(d,J＝2.0Hz),123.5(d,J＝11.8Hz),119.8(d,J＝11.8Hz),115.8(d,J＝23.0Hz),77.8,75.4,74.9,74.5,73.1,73.1,71.8,71.5,68.2,68.0,51.4,21.4.
实施例16
methyl
(E)-3-(2,4-dimethoxy-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)acrylate的制备
Figure BDA0002387057500000191
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2,4-二甲氧基碘苯0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到53.6mg目标产物，收率为72％。该化合物的核磁表征如下：1HNMR(500MHz,CDCl3)δ8.05(d,J＝16.1Hz,1H),7.37–7.24(m,15H),7.21(dd,J＝5.0,1.9Hz,3H),7.03(dd,J＝6.6,2.9Hz,2H),6.78(d,J＝2.4Hz,1H),6.69(d,J＝16.2Hz,1H),6.45(d,J＝2.4Hz,1H),5.44(d,J＝8.8Hz,1H),4.78(d,J＝12.3Hz,1H),4.61–4.56(m,2H),4.53–4.45(m,3H),4.27–4.24(m,1H),4.22–4.14(m,2H),3.96(t,J＝3.4Hz,1H),3.94–3.89(m,2H),3.87(s,3H),3.85–3.82(m,2H),3.79(s,3H),3.68(s,3H)；13C NMR(126MHz,CDCl3)δ168.3,161.2,159.8,142.1,138.8,138.5,138.4,138.2,138.1,128.3,128.2,128.2,128.0,127.6,127.6,127.6,127.5,127.4,127.3,121.2,117.0,103.9,98.1,78.1,75.4,75.3,75.2,73.1,73.1,71.7,71.6,68.2,68.1,55.6,55.3,51.2.
实施例17
methyl
(E)-3-(2-methoxy-4-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)pyridin-3-yl)acrylate的制备
Figure BDA0002387057500000201
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2-甲氧基-3-碘吡啶0.1mmol，糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到34.3mg目标产物，收率为48％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.07(d,J＝5.3Hz,1H),7.95(d,J＝16.2Hz,1H),7.37–7.32(m,2H),7.32–7.23(m,14H),7.23–7.17(m,2H),7.12(d,J＝5.4Hz,1H),7.01–6.96(m,2H),6.78(d,J＝16.2Hz,1H),5.34(d,J＝9.1Hz,1H),4.72(d,J＝12.1Hz,1H),4.63–4.55(m,2H),4.53(d,J＝10.9Hz,1H),4.52–4.42(m,2H),4.23(t,J＝6.8Hz,1H),4.19(d,J＝12.0Hz,1H),4.11(d,J＝12.0Hz,1H),4.02(s,3H),3.95–3.88(m,1H),3.87(dt,J＝8.9,2.8Hz,2H),3.80(dd,J＝4.0,1.6Hz,1H),3.75(dd,J＝10.1,6.5Hz,1H),3.70(s,3H)；13C NMR(126MHz,CDCl3)δ167.6,161.8,150.1,146.7,138.3,138.2,138.0,137.6,137.3,128.4,128.4,128.3,128.1,127.8,127.7,127.6,127.6,127.6,127.5,127.5,127.5,124.1,117.8,115.7,77.7,75.5,74.9,74.4,73.2,73.1,71.7,71.6,67.9,67.1,53.8,51.5.
实施例18
ethyl
(E)-3-(2-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)naphthalen-1-yl)acrylate的制备
Figure BDA0002387057500000211
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，1-碘萘0.1mmol，糖基氯0.15mmol，丙烯酸乙酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到67.3mg目标产物，收率为90％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.33(d,J＝16.2Hz,1H),8.07–8.00(m,1H),7.90–7.83(m,2H),7.75(d,J＝8.7Hz,1H),7.57–7.51(m,2H),7.41–7.23(m,15H),7.16(t,J＝7.3Hz,1H),7.08(t,J＝7.5Hz,2H),6.87(d,J＝7.1Hz,2H),6.48(d,J＝16.2Hz,1H),5.53(d,J＝9.4Hz,1H),4.76(d,J＝12.3Hz,1H),4.67–4.42(m,5H),4.33–4.16(m,3H),4.12(d,J＝12.0Hz,1H),4.10–4.01(m,2H),3.98(t,J＝3.3Hz,1H),3.93(dd,J＝9.9,6.9Hz,1H),3.90–3.81(m,2H),1.27(t,J＝7.1Hz,3H)；13C NMR(126MHz,CDCl3)δ166.4,142.0,138.5,138.3,138.1,137.9,135.1,132.9,132.8,131.2,128.8,128.4,128.2,128.2,128.0,127.7,127.5,127.5,127.4,127.4,127.3,127.0,126.3,126.0,125.4,124.7,77.7,75.4,75.1,74.8,73.2,73.1,71.8,71.6,68.4,68.2,60.4,14.2.
实施例19
tert-butyl
(E)-3-(2-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)naphthalen-1-yl)acrylate的制备
Figure BDA0002387057500000221
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，1-碘萘0.1mmol，糖基氯0.15mmol，丙烯酸叔丁酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到69.2mg目标产物，收率为89％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.25(d,J＝16.2Hz,1H),8.11–8.02(m,1H),7.91–7.82(m,2H),7.75(d,J＝8.7Hz,1H),7.56–7.52m,2H),7.41–7.24(m,15H),7.17(t,J＝7.4Hz,1H),7.10(t,J＝7.5Hz,2H),6.89(d,J＝7.3Hz,3H),6.40(d,J＝16.2Hz,1H),5.54(d,J＝9.4Hz,1H),4.76(d,J＝12.5Hz,1H),4.67–4.53(m,3H),4.48(dd,J＝12.1,8.3Hz,2H),4.31(t,J＝6.8Hz,1H),4.12(d,J＝12.0Hz,1H),4.11–4.02(m,2H),4.01–3.87(m,3H),3.86(dd,J＝3.9,1.5Hz,1H),1.53(s,9H)；13C NMR(126MHz,CDCl3)δ165.7,140.9,138.5,138.4,138.1,137.9,135.0,133.0,132.9,131.2,128.7,128.6,128.4,128.3,128.2,128.1,128.0,127.7,127.7,127.6,127.6,127.5,127.5,127.4,127.2,126.2,126.0,125.5,124.6,80.3,77.7,75.4,75.1,74.7,73.3,73.0,71.8,71.6,68.5,68.3,28.2.
实施例20
(2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-2-((benzyloxy)methyl)-6-(naphthalen-2-yl)tetrahydro-2H-pyran的制备
Figure BDA0002387057500000231
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，1-碘萘0.1mmol，糖基氯0.15mmol，异丙醇0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到45.5mg目标产物，收率为70％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.85–7.83(m,1H),7.81(d,J＝8.6Hz,1H),7.76–7.72(m,1H),7.70(s,1H),7.51–7.47(m,3H),7.40–7.25(m,18H),7.24–7.22(m,2H),5.21(d,J＝5.4Hz,1H),4.75–4.63(m,5H),4.62–4.56(m,2H),4.51(s,2H),4.21(dd,J＝5.4,2.9Hz,1H),4.04–3.96(m,2H),3.97–3.89(m,1H),3.86(dd,J＝10.1,3.2Hz,1H),3.83–3.80(m,1H)；13C NMR(126MHz,CDCl3)δ138.5,138.4,138.3,138.1,136.2,133.2,132.8,128.4,128.3,128.3,128.2,128.0,128.0,128.0,128.0,127.8,127.7,127.6,127.6,127.5,127.5,127.4,125.9,125.9,125.8,124.7,77.0,76.5,75.3,74.4,73.6,73.4,73.2,72.7,72.1,69.0.
实施例21
(2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-2-((benzyloxy)methyl)-6-(m-tolyl)tetrahydro-2H-pyran的制备
Figure BDA0002387057500000232
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2-甲基碘苯0.1mmol，糖基氯0.15mmol，异丙醇0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到41.8mg目标产物，收率为68％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.39–7.26(m,18H),7.24–7.19(m,2H),7.17(d,J＝7.7Hz,1H),7.13(s,1H),7.07(d,J＝7.6Hz,1H),7.03(d,J＝7.7Hz,1H),5.04(d,J＝5.0Hz,1H),4.72(d,J＝11.2Hz,1H),4.69–4.61(m,3H),4.63–4.50(m,5H),4.11(dd,J＝5.0,2.9Hz,1H),3.98(t,J＝6.6Hz,1H),3.96–3.79(m,4H),3.74(dd,J＝7.0,2.9Hz,1H),2.31(s,3H)；13C NMR(126MHz,CDCl3)δ138.5,138.4,138.3,138.3,138.0,128.3,128.3,128.3,128.3,128.2,128.2,127.9,127.9,127.8,127.7,127.6,127.6,127.5,127.5,127.4,127.4,123.7,77.3,76.3,75.4,74.1,73.7,73.6,73.2,72.6,72.0,69.1,21.4.
实施例22
(2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-2-((benzyloxy)methyl)-6-(4-fluoro-3-methylphenyl)tetrahydro-2H-pyran的制备
Figure BDA0002387057500000241
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，6-氟-2-碘甲苯0.1mmol，糖基氯0.15mmol，异丙醇0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到55.1mg目标产物，收率为87％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.37–7.27(m,16H),7.25–7.22(M,4H),7.15(dd,J＝7.5,2.2Hz,1H),7.05–7.02(m,1H),6.92(t,J＝8.9Hz,1H),4.94(d,J＝6.0Hz,1H),4.70–4.59(m,4H),4.56(dd,J＝11.8,6.7Hz,2H),4.50–4.40(m,2H),4.01–3.90(m,3H),3.88(dd,J＝10.2,6.2Hz,1H),3.81(dd,J＝10.2,4.3Hz,1H),3.76(dd,J＝6.2,2.9Hz,1H),2.23(s,3H)；13C NMR(126MHz,CDCl3)δ160.7(d,J＝244.4Hz),138.4,138.2,138.2,138.0,134.2(d,J＝3.0Hz),130.0(d,J＝5.2Hz),128.4,128.3,128.2,127.9,127.9,127.8,127.7,127.7,127.6,127.6,127.5,127.5,125.8(d,J＝7.9Hz),124.6(d,J＝17.3Hz),114.7(d,J＝22.0Hz),76.5,76.4,75.1,74.3,73.2,73.1,72.7,72.7,71.9,68.8,14.5(d,J＝3.6Hz).
实施例23
(2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-2-((benzyloxy)methyl)-6-(4-chloro-3-methylphenyl)tetrahydro-2H-pyran的制备
Figure BDA0002387057500000251
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，6-氯-2-碘甲苯0.1mmol，糖基氯0.15mmol，异丙醇0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到55.7mg目标产物，收率为86％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.37–7.27(m,16H),7.26–7.21(m,5H),7.19(s,1H),7.01(dd,J＝8.3,2.1Hz,1H),4.93(d,J＝5.9Hz,1H),4.69–4.59(m,4H),4.56(dd,J＝11.8,7.3Hz,2H),4.50–4.40(m,2H),4.00–3.93(m,2H),3.92(t,J＝5.8Hz,1H),3.87(dd,J＝10.2,6.4Hz,1H),3.79(dd,J＝10.3,4.3Hz,1H),3.73(dd,J＝6.2,2.9Hz,1H),2.32(s,3H)；13C NMR(126MHz,CDCl3)δ138.3,138.2,138.1,138.0,137.3,135.8,133.4,129.4,128.8,128.4,128.3,128.3,128.2,128.0,127.9,127.8,127.7,127.7,127.6,127.6,127.5,125.6,76.5,76.3,75.1,75.0,74.4,74.3,73.2,72.7,71.9,68.8,20.0.
实施例24
methyl
2-methyl-4-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)benzoate的制备
Figure BDA0002387057500000261
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，3-碘-2-甲基苯甲酸甲酯0.1mmol，糖基氯0.15mmol，异丙醇0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到55.8mg目标产物，收率为83％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.87(d,J＝8.1Hz,1H),7.37–7.27(m,16H),7.23(dt,J＝5.7,1.8Hz,5H),7.16(dd,J＝8.2,1.7Hz,1H),4.99(d,J＝6.0Hz,1H),4.69–4.61(m,4H),4.59–4.52(m,2H),4.50–4.41(m,2H),4.02–3.96(m,2H),3.95–3.85(m,5H),3.80(dd,J＝10.3,4.3Hz,1H),3.73(dd,J＝6.3,2.9Hz,1H),2.57(s,3H)；13C NMR(126MHz,CDCl3)δ167.8,142.9,140.3,138.3,138.2,138.1,137.9,130.6,130.1,128.6,128.4,128.3,128.3,128.3,128.2,127.9,127.9,127.8,127.7,127.7,127.6,127.5,124.1,76.5,76.4,75.0,75.0,74.5,73.1,72.9,72.7,72.0,68.7,51.7,21.7.
实施例25
(2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-2-((benzyloxy)methyl)-6-(3-chloro-5-methylphenyl)tetrahydro-2H-pyran的制备
Figure BDA0002387057500000271
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，4-氯-1-碘-2-甲苯0.1mmol，糖基氯0.15mmol，异丙醇0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到52.5mg目标产物，收率为81％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.44–7.27(m,16H),7.26–7.22(m,4H),7.15(s,1H),7.08(s,1H),7.02(s,1H),4.92(d,J＝6.1Hz,1H),4.67–4.61(m,4H),4.59–4.51(m,2H),4.49–4.36(m,2H),4.05–3.84(m,4H),3.83–3.69(m,2H),2.29(s,3H)；13C NMR(126MHz,CDCl3)δ140.7,139.7,138.3,138.2,138.1,137.9,134.0,128.4,128.4,128.3,128.3,127.9,127.9,127.8,127.8,127.7,127.6,127.5,125.8,124.1,76.5,76.4,76.2,75.0,74.4,73.1,72.7,72.7,72.0,68.6,21.2.
实施例26
methyl
3-methyl-5-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)benzoate的制备
Figure BDA0002387057500000272
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，4-碘-3-甲基苯甲酸甲酯0.1mmol，糖基氯0.15mmol，异丙醇0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到55.1mg目标产物，收率为82％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.88(s,1H),7.79(s,1H),7.38(s,1H),7.36–7.25(m,16H),7.25–7.22(m,2H),7.17(dd,J＝6.5,2.9Hz,2H),4.98(d,J＝6.6Hz,1H),4.72–4.53(m,6H),4.41(d,J＝11.9Hz,1H),4.34(d,J＝12.0Hz,1H),4.08–3.99(m,2H),3.94–3.86(m,5H),3.84–3.74(m,2H),2.36(s,3H)；13C NMR(126MHz,CDCl3)δ167.1,139.4,138.3,138.2,138.2,138.1,137.9,132.3,130.1,129.4,128.5,128.4,128.3,128.2,127.9,127.9,127.8,127.7,127.6,127.5,127.5,126.9,125.4,76.1,74.9,74.5,73.1,72.9,72.7,72.6,72.0,68.6,52.0,21.2.
实施例27
N-methoxy-N,3-dimethyl-5-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)benzamide的制备
Figure BDA0002387057500000281
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，4-碘-N-甲氧基-N，3-二甲基苯甲酰胺0.1mmol，糖基氯0.15mmol，异丙醇0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到54.7mg目标产物，收率为78％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.45(s,1H),7.37(s,1H),7.35–7.27m,16H),7.26–7.21(m,5H),5.01(d,J＝5.7Hz,1H),4.70–4.51(m,6H),4.51–4.41(m,2H),4.06(dd,J＝5.8,2.9Hz,1H),4.00–3.90(m,2H),3.87(dd,J＝10.2,6.0Hz,1H),3.80(dd,J＝10.2,4.0Hz,1H),3.75(dd,J＝6.2,2.9Hz,1H),3.49(s,3H),3.31(s,3H),2.33(s,3H)；13C NMR(126MHz,CDCl3)δ170.0,138.6,138.3,138.2,138.1,138.0,137.9,134.3,129.6,128.3,128.3,128.2,128.2,127.9,127.8,127.8,127.8,127.7,127.6,127.6,127.5,127.4,123.6,76.7,76.4,75.1,74.3,73.2,73.2,73.1,72.5,72.0,68.9,60.9,34.0,21.3.
实施例28
(2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-2-((benzyloxy)methyl)-6-(3,5-dimethoxyphenyl)tetrahydro-2H-pyran
Figure BDA0002387057500000291
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将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2,4-二甲氧基碘苯0.1mmol，糖基氯0.15mmol，异丙醇0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到35.6mg目标产物，收率为54％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.39–7.24(m,18H),7.20(dd,J＝7.4,2.0Hz,2H),6.49(d,J＝2.2Hz,2H),6.35(t,J＝2.3Hz,1H),5.02(d,J＝4.5Hz,1H),4.73(d,J＝11.2Hz,1H),4.66–4.53(m,6H),4.52(d,J＝11.3Hz,1H),4.11(dd,J＝4.6,2.9Hz,1H),3.96–3.88(m,2H),3.83(d,J＝4.0Hz,2H),3.72(q,J＝3.1Hz,1H),3.69(s,6H)；13C NMR(126MHz,CDCl3)δ160.9,140.7,138.3,138.3,138.2,138.2,128.4,128.3,128.3,128.3,128.0,128.0,127.8,127.8,127.8,127.7,127.6,127.5,104.5,99.6,78.0,75.9,75.2,74.2,73.9,73.8,73.3,72.4,72.0,69.4,55.3.
实施例29
triisopropyl((2-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)naphthalen-1-yl)ethynyl)silane的制备
Figure BDA0002387057500000301
将碳酸钾0.3mmol，((1R，4R)-N-甲基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，1-碘萘0.15mmol，糖基氯0.15mmol，三异丙基硅基乙炔0.1mmol,乙腈1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到46.5mg目标产物，收率为56％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.50(d,J＝8.3Hz,1H),7.82(t,J＝8.0Hz,2H),7.72(d,J＝8.6Hz,1H),7.59(t,J＝7.3Hz,1H),7.51(t,J＝7.2Hz,1H),7.39–7.20(m,15H),7.16–7.05(m,3H),6.94(d,J＝7.2Hz,2H),5.87(d,J＝9.2Hz,1H),4.69–4.55(m,4H),4.50(dd,J＝20.2,12.1Hz,2H),4.34(t,J＝7.0Hz,1H),4.16(dd,J＝9.5,7.6Hz,1H),4.06(d,J＝11.8Hz,1H),4.01–3.87(m,5H),1.17(s,21H)；13C NMR(126MHz,CDCl3)δ140.8,138.6,138.5,138.3,138.2,133.5,132.7,128.6,128.4,128.3,128.2,128.0,127.8,127.7,127.7,127.6,127.5,127.5,127.4,127.4,127.0,126.8,126.8,126.2,124.3,120.9,102.6,100.6,77.6,75.1,74.8,74.2,73.2,72.8,71.7,71.5,70.3,68.9,18.9,18.8,11.4.
实施例30
triisopropyl((2-methyl-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)ethynyl)silane的制备
Figure BDA0002387057500000302
将碳酸钾0.3mmol，((1R，4R)-N-甲基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，2-甲基碘苯0.15mmol，糖基氯0.15mmol，三异丙基硅基乙炔0.1mmol,乙腈1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到33.3mg目标产物，收率为42％。该化合物的核磁表征如下：1HNMR(500MHz,CDCl3)δ7.44(d,J＝7.6Hz,1H),7.39–7.27(m,10H),7.27–7.20(m,9H),7.16(d,J＝7.3Hz,1H),7.07(dd,J＝6.5,2.9Hz,1H),5.68(d,J＝9.1Hz,1H),4.67–4.55(m,4H),4.50(dd,J＝15.7,12.1Hz,2H),4.29(t,J＝6.9Hz,1H),4.18–4.10(m,2H),4.00–3.88(m,4H),3.87(dd,J＝9.1,2.9Hz,1H),2.51(s,3H),1.11(s,21H)；13C NMR(126MHz,CDCl3)δ142.3,140.7,138.6,138.6,138.6,138.3,128.6,128.4,128.3,128.1,127.9,127.9,127.7,127.6,127.6,127.5,127.4,127.4,127.3,127.0,124.2,123.7,103.5,99.4,78.4,75.0,74.8,74.5,73.2,72.6,71.8,71.6,70.1,69.0,21.6,18.7,18.9,11.3.
实施例31
((4-chloro-2-methyl-6-((2R,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)phenyl)ethynyl)triisopropylsilane的制备
Figure BDA0002387057500000311
将碳酸钾0.3mmol，((1R，4R)-N-甲基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，4-氯-1-碘-2-甲苯0.15mmol，糖基氯0.15mmol，三异丙基硅基乙炔0.1mmol,乙腈1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到38.9mg目标产物，收率为47％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.43–7.18(m,19H),7.14(d,J＝2.1Hz,1H),7.03(dd,J＝6.5,3.0Hz,2H),5.60(d,J＝9.3Hz,1H),4.63–4.51(m,4H),4.47(dd,J＝12.1,10.2Hz,2H),4.27(t,J＝7.0Hz,1H),4.17(d,J＝11.7Hz,1H),4.05(dd,J＝9.6,7.5Hz,1H),3.99–3.88(m,3H),3.85(dd,J＝3.6,1.4Hz,1H),3.76(dd,J＝9.3,2.8Hz,1H),2.46(s,3H),1.09(s,21H)；13C NMR(126MHz,CDCl3)δ144.1,142.3,138.4,138.4,138.2,138.1,133.9,128.7,128.4,128.3,128.2,127.9,127.8,127.7,127.6,127.5,127.5,127.4,127.2,124.5,122.4,102.6,100.3,78.2,75.1,74.5,73.8,73.2,72.6,71.6,71.5,69.5,68.7,21.5,18.8,18.7,11.3.
实施例32
methyl
(E)-3-(2-((2R,3R,4R,5R,6R)-3,4,5-trimethoxy-6-(methoxymethyl)tetrahydro-2H-pyran-2-yl)naphthalen-1-yl)acrylate的制备
Figure BDA0002387057500000321
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，1-碘萘0.1mmol，糖基氯0.15mmol，异丙醇0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到39.6mg目标产物，收率为92％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.30(d,J＝16.3Hz,1H),8.04–7.95(m,1H),7.88–7.79(m,2H),7.73(d,J＝8.7Hz,1H),7.53–7.45(m,2H),6.36(d,J＝16.3Hz,1H),5.28(d,J＝9.2Hz,1H),4.16(t,J＝6.6Hz,1H),3.89–3.87(m,4H),3.85–3.77(m,2H),3.66(dd,J＝10.0,6.2Hz,1H),3.65–3.60(m,1H),3.56(s,3H),3.49(s,3H),3.39(s,3H),3.04(s,3H)；13C NMR(126MHz,CDCl3)δ166.8,142.4,134.8,132.9,131.2,128.7,128.2,126.4,126.4,126.1,125.4,124.7,79.1,76.5,74.1,70.5,68.2,59.1,59.0,57.7,51.7.
实施例33
methyl
(E)-3-(2-((3aR,4R,5aR,9aR,9bR)-2,2,8,8-tetramethylhexahydro-[1,3]dioxolo[4',5':4,5]pyrano[3,2-d][1,3]dioxin-4-yl)naphthalen-1-yl)acrylate的制备
Figure BDA0002387057500000331
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，1-碘萘0.1mmol，D-甘露糖吡喃糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到28.2mg目标产物，收率为62％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.23(d,J＝16.2Hz,1H),8.07–8.01(m,1H),7.89–7.82(m,2H),7.55–7.50(m,2H),7.38(d,J＝8.6Hz,1H),6.31(d,J＝16.3Hz,1H),5.41(d,J＝1.5Hz,1H),4.93(d,J＝2.7Hz,2H),4.54–4.47(m,1H),4.17–4.10(m,3H),3.87(s,3H),1.61(s,3H),1.46(s,3H),1.40(s,3H),1.38(s,3H)；13C NMR(126MHz,CDCl3)δ166.5,141.4,134.9,132.8,131.6,131.4,129.0,128.3,126.9,126.9,126.3,125.1,123.0,113.3,109.2,87.2,83.8,81.7,81.4,73.7,66.9,51.8,26.9,26.6,25.3,25.0.
实施例34
methyl
(E)-3-(2-((3aS,4R,5aR,9aS,9bR)-2,2,8,8-tetramethylhexahydro-[1,3]dioxolo[4',5':4,5]pyrano[3,2-d][1,3]dioxin-4-yl)naphthalen-1-yl)acrylate的制备
Figure BDA0002387057500000341
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，1-碘萘0.1mmol，D-半乳糖吡喃糖基氯0.15mmol,丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到19.6mg目标产物，收率为43％。该化合物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.43(d,J＝16.3Hz,1H),8.18(d,J＝8.5Hz,1H),7.99(d,J＝8.6Hz,1H),7.88(t,J＝7.9Hz,2H),7.60(t,J＝7.2Hz,2H),7.57–7.53(m,2H),6.09(d,J＝16.3Hz,1H),5.57(d,J＝5.0Hz,1H),4.66(dd,J＝7.9,2.5Hz,1H),4.56(dd,J＝11.5,4.9Hz,1H),4.44(dd,J＝11.5,7.6Hz,1H),4.38–4.31(m,2H),4.22–4.15(m,1H),3.86(s,3H),1.51(s,3H),1.48(s,3H),1.36(s,3H),1.33(s,3H)；13C NMR(126MHz,CDCl3)δ167.0,166.5,143.5,136.4,135.2,130.9,128.6,128.3,128.0,127.1,126.7,125.7,124.8,109.7,108.8,96.3,71.1,70.8,70.5,66.0,64.3,51.8,26.0,26.0,25.0,24.5.
实施例35
methyl
(E)-3-(2-((2S,3S,4R,5S,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)naphthalen-1-yl)acrylate的制备
Figure BDA0002387057500000351
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，1-碘萘0.1mmol，L-鼠李糖糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到61.5mg目标产物，收率为98％。该化合物的核磁表征如下：1HNMR(500MHz,CDCl3)δ8.34(d,J＝16.2Hz,1H),8.07–8.01(m,1H),7.92–7.81(m,2H),7.71(d,J＝8.6Hz,1H),7.53(dd,J＝6.4,3.2Hz,2H),7.44–7.27(m,10H),7.17(t,J＝7.3Hz,1H),7.10(t,J＝7.5Hz,2H),6.91(d,J＝7.5Hz,2H),6.50(d,J＝16.2Hz,1H),5.60(d,J＝9.1Hz,1H),4.85(d,J＝12.2Hz,1H),4.66(d,J＝12.3Hz,1H),4.60(d,J＝12.1Hz,1H),4.51(d,J＝12.1Hz,1H),4.25–4.05(m,4H),4.01(t,J＝3.3Hz,1H),3.74(s,3H),3.60(d,J＝2.2Hz,1H),1.48(d,J＝7.1Hz,3H)；13C NMR(126MHz,CDCl3)δ166.8,142.3,138.8,138.2,137.9,135.2,132.9,132.8,131.2,128.8,128.4,128.3,128.2,128.0,127.7,127.6,127.6,127.5,127.4,127.3,126.5,126.4,126.0,125.3,124.6,78.8,77.9,75.5,73.3,72.3,71.8,71.8,67.1,51.6,17.0.
实施例36
methyl
(E)-3-(2-((3aS,4R,6R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)naphthalen-1-yl)acrylate的制备
Figure BDA0002387057500000361
将碳酸铯0.3mmol，(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺0.2mmol，醋酸钯0.01mmol，三(2-呋喃基)膦0.02mmol，1-碘萘0.1mmol，D-呋喃核糖糖基氯0.15mmol，丙烯酸甲酯0.2mmol,四氢呋喃1mL加入到15mL的反应管中，氮气反复填充10次，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,薄层色谱纯化得到31.7mg目标产物，收率为51％。该化合物的核磁表征如下：1HNMR(500MHz,CDCl3)δ8.29(d,J＝16.2Hz,1H),8.04–7.99(m,1H),7.85–7.80(m,1H),7.79–7.70(m,6H),7.53–7.48(m,1H),7.46–7.41(m,1H),7.40–7.35(m,2H),6.35(d,J＝16.2Hz,1H),5.27(d,J＝6.0Hz,1H),4.91(dd,J＝6.7,3.6Hz,1H),4.62(t,J＝6.3Hz,1H),4.22(q,J＝3.3Hz,1H),4.04(dd,J＝11.3,3.0Hz,1H),3.91(dd,J＝11.3,3.3Hz,1H),3.85(s,3H),1.63(s,3H),1.35(s,3H),1.13(s,9H)；13C NMR(126MHz,CDCl3)δ166.6,141.6,135.7,135.6,135.2,134.8,133.2,133.1,132.9,131.4,131.0,129.8,129.7,129.6,129.1,128.2,127.8,127.8,127.7,127.0,126.6,126.2,125.3,124.0,114.8,87.2,84.2,82.3,81.9,64.0,51.7,27.5,26.9,26.5,25.7,19.3.
本领域技术人员可知，当本发明的技术参数在如下范围内变化时，可以预期得到与上述实施例相同或相近的技术效果：
一种C-芳基糖苷化合物的制备方法，其特征在于：包括如下步骤：
(1)向经氮气吹扫的反应容器中依次加入碱、助催化剂、钯催化剂、配体、卤代芳烃、糖基氯化物、终止试剂和有机溶剂，于90～110℃反应24h，得到混合物料；
其中，所述碱、助催化剂、钯催化剂、配体、卤代芳烃、糖基氯化物和终止试剂的摩尔比为3:2:0.1:0.2:1:1.5:2，且每摩尔卤代芳烃对应的有机溶剂为1～2L。
所述卤代芳烃的结构式为
Figure BDA0002387057500000371
其中X为卤素，所述R为氟、碘、氯或溴、甲基、三氟甲基、甲氧基、羧酸酯基和酰胺基；所述钯催化剂为醋酸钯，所述配体为三(2-呋喃基)膦，所述碱为碳酸铯或碳酸钾，所述有机溶剂为四氢呋喃或乙腈。
(2)将步骤(1)所得的混合物料经乙酸乙酯稀释后，再经水洗，分离得有机相；
(3)将步骤(2)所得的有机相经干燥、过滤、浓缩、薄层色谱或柱层析色谱，得到所述C-芳基糖苷化合物。
以上所述，仅为本发明较佳实施例而已，故不能依此限定本发明实施的范围，即依本发明专利范围及说明书内容所作的等效变化与修饰，皆应仍属本发明涵盖的范围内。

Claims (2)

1.一种C-芳基糖苷化合物的制备方法，其特征在于：包括如下步骤：
(1)向经氮气吹扫的反应容器中依次加入碱、助催化剂、钯催化剂、配体、卤代芳烃、糖基氯化物、终止试剂和有机溶剂，于80～120℃反应15～30h，得到混合物料；
其中，所述碱、助催化剂、钯催化剂、配体、卤代芳烃、糖基氯化物和终止试剂的摩尔比为1.8～3.5:1.0～2.5:0.08～0.12:0.18～0.22:0.8～1.2:1.0～2.0:1.0～2.5，且每摩尔卤代芳烃对应的有机溶剂为1～3L；所述碱为碳酸钾或碳酸铯；所述助催化剂为(1R，4R)-N-苯基双环[2.2.1]庚-5-烯-2-羧酰胺；所述钯催化剂为醋酸钯；所述配体为三(2-呋喃基)膦；所述终止试剂为丙烯酸甲酯、丙烯酸乙酯、丙烯酸叔丁酯、异丙醇或三异丙基硅基乙炔；所述有机溶剂为乙腈或四氢呋喃；所述卤代芳烃为1-碘萘、2-甲基碘苯、2-甲氧基碘苯、2-氟碘苯、2-氯碘苯、3-碘邻二甲苯、2-氟-6-碘-甲苯、2-氯-6-碘甲苯、3-碘-2-甲基苯甲酸甲酯、4-碘间二甲苯、4-氟-1-碘-2-甲苯、4-氯-1-碘-2-甲苯、4-碘-2-甲基苯甲酸甲酯、4-碘-N-甲氧基-N，3-二甲基苯甲酰胺、2-氟-1-碘-4-甲苯、2,4-二甲氧基碘苯、2-甲氧基-3-碘吡啶；所述糖基氯化物包括
Figure FDA0004176853410000011
(2)将步骤(1)所得的混合物料经乙酸乙酯稀释后，再经水洗，分离得有机相；
(3)将步骤(2)所得的有机相经干燥、过滤、浓缩、薄层色谱或柱层析色谱，得到所述C-芳基糖苷化合物。
2.根据权利要求1所述的一种C-芳基糖苷化合物的制备方法，其特征在于：所述步骤(1)中，向经氮气吹扫的反应容器中依次加入碱、助催化剂、钯催化剂、配体、卤代芳烃、糖基氯化物、终止试剂和有机溶剂，于90～110℃反应24h，得到混合物料；
其中，所述碱、助催化剂、钯催化剂、配体、卤代芳烃、糖基氯化物和终止试剂的摩尔比为3:2:0.1:0.2:1:1.5:2，且每摩尔卤代芳烃对应的有机溶剂为1～2L。
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