CN111018869B - 手性稠环吡喃并二氢吡咯类化合物的制备方法 - Google Patents

手性稠环吡喃并二氢吡咯类化合物的制备方法 Download PDF

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CN111018869B
CN111018869B CN201911115811.5A CN201911115811A CN111018869B CN 111018869 B CN111018869 B CN 111018869B CN 201911115811 A CN201911115811 A CN 201911115811A CN 111018869 B CN111018869 B CN 111018869B
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毕晶晶
孙潇潇
郝玉伟
谭强
陈长坡
张贵生
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Abstract

本发明公开了一种手性稠环吡喃并二氢吡咯类化合物的制备方法，具体步骤为：向装有磁子的烧瓶中加入烯糖类化合物1和催化剂Rh2(TFA)4，再加入溶剂DCE进行溶解，于60~100℃搅拌反应，将1,2,3‑三氮唑类化合物2的DCE溶液滴加到上述混合体系中，滴加完毕后继续反应0.5小时，TLC检测反应完毕后减压蒸馏除去溶剂，经硅胶柱色谱分离得到目标产物。本发明的反应底物普适性广，反应条件温和，操作简单且收率较高。

Description

手性稠环吡喃并二氢吡咯类化合物的制备方法
技术领域
本发明属于有机合成技术领域，具体涉及一种手性稠环吡喃并二氢吡咯类化合物的制备方法。
背景技术
环加成反应是两个或多个分子的环合反应，它可以对化合物进行并环形成稠环类化合物，或者对直链化合物进行环合得到各种不同环系的化合物。近年来，过渡金属催化进行的环加成反应是化学研究的热点，尤其是铑催化的环加成反应，它以高立体选择性和转化率可以高效地合成含特定构型的化合物，这对手性药物化合物的合成具有重要的意义和应用前景。近些年，N-磺酰基-1,2,3-***的开环衍生的α-亚氨基铑卡宾配合物引起了有机化学家的关注，它能进行各种化合物，特别是含氮杂环类化合物的合成。
稠合双环缩醛和N-杂缩醛类化合物普遍存在于许多生物活性天然产物中作为关键骨架结构。这些双环缩醛的主要部分以呋喃并[2,3-b]吡喃、呋喃并[2,3-b]呋喃、吡咯并[2,3-b]吡喃及吡咯并[2,3-b]呋喃]等形式存在。其中，具有手性稠环吡喃并二氢吡咯类化合物是重要的一类衍生物。由于结构中存在多手性碳，其合成方法相当不容易，很难大范围推广应用。本发明利用稠环糖的优良手性，作为底物与N-磺酰基-1,2,3-***反应，可简单高效的合成各种手性稠环吡喃并二氢吡咯类化合物。
发明内容
本发明解决的技术问题是提供了一种简单高效的手性稠环吡喃并二氢吡咯类化合物的制备方法，该方法以Rh2(TFA)4为催化剂反应得到预期产物，并且通过糖环自身的手性可以高区域选择性的得到单一构型产物。
本发明为解决上述技术问题采用如下技术方案，手性稠环吡喃并二氢吡咯类化合物的制备方法，其特征在于具体步骤为：向装有磁子的烧瓶中加入烯糖类化合物2和催化剂Rh2(TFA)4，再加入溶剂二氯乙烷(DCE)进行溶解，于60～100℃搅拌反应，将1,2,3-三氮唑类化合物1的DCE溶液滴加到上述混合体系中，滴加完毕后继续反应0.5小时，TLC检测反应完毕后减压蒸馏除去溶剂，经硅胶柱色谱分离得到目标产物；
合成过程中的反应方程式如下：
Figure GDA0003463908940000011
对应目标产物的化学式如下：
Figure GDA0003463908940000021
Figure GDA0003463908940000031
进一步限定，所述化合物1、化合物2与催化剂的投料摩尔比为2～3:1:0.02。
本发明与现有技术相比具有以下有益效果：本发明的反应底物普适性广，反应条件温和，操作简单且收率较高。
具体实施方式
以下通过实施例对本发明的上述内容做进一步详细说明，但不应该将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例
条件优化：
Figure GDA0003463908940000032
我们以4-苯基-1-对甲苯磺酰基-1,2,3-三氮唑1a和廉价易得的3,4,6-三-O-乙酰基-D-葡萄烯糖2a为反应底物，进行了一系列条件优化。首先将反应温度改变至60℃和100℃，都没有取得令人满意的效果，最终我们将反应温度确定为80℃。同时，我们又对反应的溶剂进行了筛选，发现DCE作为反应溶剂效果最好。接下来，我们又对反应底物的比例、浓度、催化剂用量进行了优化(表1)。
综上所述，我们得到了最优反应条件即以1a：2a：Rh2(TFA)4＝2:1:0.02的投料摩尔比，反应温度为80℃，DCE为溶剂，反应0.5小时作为最优的反应条件。
表1反应条件的优化
Figure GDA0003463908940000041
各种手性稠环吡喃并二氢吡咯类化合物的制备方法
底物与烯糖反应生成目标物的实验操作步骤：向装有磁力搅拌子的25mL史莱克管中加入烯糖(0.2mmol)和催化剂Rh2(TFA)4(0.004mmol)，再加入干燥的DCE(0.5mL)使之溶解，于80℃搅拌反应，将1,2,3-三氮唑(0.4mmol)的DCE(3mL)溶液滴加进上述混合体系，滴加完毕后继续反应0.5小时，TLC检测反应完毕后减压蒸馏除去溶剂，经硅胶柱色谱(200-300目)分离得到白色固体。
实验结果：
表2不同取代芳基产物
Figure GDA0003463908940000042
Figure GDA0003463908940000051
表3不同磺酰基产物
Figure GDA0003463908940000052
表4含不同保护基糖产物
Figure GDA0003463908940000053
Figure GDA0003463908940000061
目标产物数据：
Figure GDA0003463908940000062
Spectral data of 3a white solid,yield 80％,m.p.197-198℃,1H NMR(400MHz,CDCl3)δ7.76(d,J＝8.4Hz,2H),7.33-7.29(m,6H),7.22(t,J＝6.8Hz,1H),6.94(d,J＝1.6Hz,1H),5.62(d,J＝8.8Hz,1H),5.15(t,J＝4.4Hz,1H),4.88(dd,J＝8.0,4.0Hz,1H),4.16(dd,J＝11.6,4.4Hz,1H),3.98(dd,J＝8.0,2.8Hz,1H),3.93(dd,J＝11.6,2.8Hz,1H),3.65(dd,J＝8.4,4.4Hz,1H),2.43(s,3H),2.10(s,3H),1.95(s,3H),1.61(s,3H)；13CNMR(100MHz,CDCl3)δ170.8,169.9,169.6,144.8,134.8,132.4,130.2,128.9,127.7,127.6,126.8,125.6,121.9,88.0,70.4,68.6,68.2,63.0,44.2,21.7,20.9,20.9,20.3.ESI(+)-HRMS(m/z):[M+Na]+calcd.for C27H29NO9SNa 556.1455,found 556.1444。
Figure GDA0003463908940000063
Spectral data of 3b white solid,yield 83％,m.p.183-184℃,1H NMR(400MHz,CDCl3)δ7.75(d,J＝8.0Hz,2H),7.32(d,J＝8.0Hz,2H),7.27(d,J＝8.8Hz,2H),6.85(d,J＝8.4Hz,2H),6.82(s,1H),5.57(d,J＝8.4Hz,1H),5.13(t,J＝4.4Hz,1H),4.87(dd,J＝8.0,4.0Hz,1H),4.18(dd,J＝11.6,4.8Hz,1H),3.99-3.93(m,2H),3.79(s,3H),3.58(dd,J＝8.0,4.8Hz,1H),2.43(s,3H),2.10(s,3H),1.95(s,3H),1.67(s,3H)；13C NMR(100MHz,CDCl3)δ170.8,169.9,169.7,159.3,144.7,134.6,130.2,127.6,126.9,125.2,124.9,121.9,114.3,88.0,70.6,68.6,68.2,63.0,55.5,44.5,21.8,21.7,21.0,20.9,20.4.ESI(+)-HRMS m/z calcd for C28H31NO10SNa[M+Na]+596.1561,found 596.1542。
Figure GDA0003463908940000071
Spectral data of 3d white solid,yield 45％,m.p.63-64℃,1H NMR(400MHz,CDCl3)δ7.79(d,J＝8.4Hz,2H),7.39-7.34(m,3H),7.29(dd,J＝7.6,2.0Hz,1H),7.24(dd,J＝8.0,1.6Hz,1H),7.19(dd,J＝8.0,2.0Hz,1H),7.09(d,J＝2.0Hz,1H),5.71(d,J＝8.4Hz,1H),4.95(t,J＝4Hz,1H),4.87(dd,J＝8.4,4.4Hz,1H),4.05(dd,J＝12.0,4.4Hz,1H),3.90-3.84(m,2H),3.78(dd,J＝12.0,2.8Hz,1H),2.45(s,3H),2.08(s,3H),1.88(s,3H),1.74(s,3H)；13C NMR(100MHz,CDCl3)δ170.8,169.8,169.6,145.0,134.8,134.5,134.3,130.2,128.0,127.7,127.6,125.7,123.5,120.7,88.4,70.9,68.8,67.9,62.7,44.3,21.8,21.0,20.4.ESI(+)-HRMS m/z calcd for C27H28NO9SClNa[M+Na]+600.1066,found600.1061.
Figure GDA0003463908940000072
Spectral data of 3e white solid,yield 53％,m.p.194-195℃,1H NMR(400MHz,CDCl3)δ7.77(d,J＝8.4Hz,2H),7.36(s,1H),7.33(d,J＝4.8Hz,1H),7.24-7.20(m,2H),6.98(d,J＝1.2Hz,1H),5.60(d,J＝8.8Hz,1H),5.10(t,J＝4.8Hz,1H),4.91(dd,J＝8.8,4.4Hz,1H),4.17(dd,J＝12.4,4.4Hz,1H),3.94-3.89(m,2H),3.58(dd,J＝8.8,4.8Hz,1H),2.44(s,3H),2.09(s,3H),1.96(s,3H),1.71(s,3H)；13C NMR(150MHz,CDCl3)δ170.8,169.9,169.6,145.0,134.8,134.5,134.3,130.2,128.0,127.7,125.6,123.5,120.8,88.4,70.9,68.9,68.0,62.8,44.3,21.8,20.9,20.4.ESI(+)-HRMS m/z calcd forC27H28NO9SClNa[M+Na]+600.1066,found 600.1043。
Figure GDA0003463908940000073
Spectral data of 3f white solid,yield 80％,m.p.214-215℃,1H NMR(600MHz,CDCl3)δ7.82(d,J＝8.4Hz,2H),7.52(d,J＝8.4Hz,2H),7.35-7.31(m,2H),7.24(t,J＝7.2Hz,1H),6.91(s,1H),5.63(d,J＝9.0Hz,1H),5.16(t,J＝4.2Hz,1H),4.87(dd,J＝8.4,3.8Hz,1H),4.18(dd,J＝12.0,5.4Hz,1H),4.02(dd,J＝12.0,2.4Hz,1H),3.98(ddd,J＝8.4,5.4,3.0Hz,1H),3.68(dd,J＝7.2,4.2Hz,1H),2.10(s,3H),1.96(s,3H),1.61(s,3H),1.58(s,3H)；13C NMR(100MHz,CDCl3)δ170.8,169.9,169.5,144.9,134.7,133.4,130.9,130.2,129.8,129.1,127.6,127.4,126.8,126.6,120.7,88.1,70.4,68.6,68.1,62.9,44.2,21.8,21.0,20.9,20.4.ESI(+)-HRMS m/z calcd for C27H28NO9SClNa[M+Na]+600.1066,found 600.1059。
Figure GDA0003463908940000081
Spectral data of 3h white solid,yield 73％,m.p.119-120℃,1H NMR(400MHz,CDCl3)δ7.76(d,J＝8.0Hz,2H),7.34-7.30(m,4H),7.02(t,J＝8.4Hz,2H),6.88(s,1H),5.61(d,J＝8.8Hz,1H),5.09(t,J＝4.0Hz,1H),4.88(dd,J＝8.4,3.6Hz,1H),4.15(dd,J＝12.0,5.2Hz,1H),3.95-3.91(m,1H),3.60(dd,J＝7.6,4.8Hz,1H),2.43(s,3H),2.09(s,3H),1.95(s,3H),1.67(s,3H)；13C NMR(100MHz,CDCl3)δ170.8,169.9,169.5,144.9,134.7,130.2,128.6,127.6,127.3,127.2,126.6,120.9,116.0,115.8,88.0,70.6,68.6,68.1,62.9,44.4,21.8,21.0,20.9,20.4.ESI(+)-HRMS m/z:calcd for C27H28FNO9SNa[M+Na]+584.1347,found 584.1361。
Figure GDA0003463908940000082
Spectral data of 3j white solid,yield 74％,m.p.1H NMR(600MHz,CDCl3)δ7.76(d,J＝7.8Hz,2H),7.45(d,J＝7.8Hz,2H),7.34(d,J＝7.8Hz,2H),7.22(d,J＝7.8Hz,2H),6.96(s,1H),5.63(d,J＝8.4Hz,1H),5.09(t,J＝4.2Hz,1H),4.88(dd,J＝8.4,3.6Hz,1H),4.14(dd,J＝12.0,4.8Hz,1H),3.92-3.90(m,2H),3.60(dd,J＝7.8,4.8Hz,1H),2.44(s,3H),2.09(s,3H),1.96(s,3H),1.68(s,3H)；13C NMR(100MHz,CDCl3)δ170.8,169.9,169.6,145.0,134.7,132.0,130.2,129.8,127.6,127.4,127.0,126.6,121.4,120.7,88.1,70.4,68.7,68.1,62.9,44.2,21.8,21.0,20.9,20.4.ESI(+)-HRMS m/z:calcd forC27H28BrNO9SNa[M+Na]+644.0544,found 644.0560。
Figure GDA0003463908940000091
Spectral data of 3l white solid,yield 84％,m.p.178-179℃,1H NMR(600MHz,CDCl3)δ7.75(d,J＝7.8Hz,2H),7.32(d,J＝8.4Hz,2H),7.23(d,J＝7.8Hz,2H),7.12(d,J＝7.8Hz,2H),6.89(s,1H),5.59(d,J＝9.0Hz,1H),5.14(t,J＝4.2Hz,1H),4.87(dd,J＝7.8,3.6Hz,1H),4.17(dd,J＝12.0,4.8Hz,1H),3.99-3.93(m,2H),3.60(dd,J＝7.2,5.4Hz,1H),2.43(s,3H),2.31(s,3H),2.10(s,3H),1.95(s,3H),1.64(s,3H)；13C NMR(150MHz,CDCl3)δ170.9,169.9,169.7,144.7,137.7,134.7,130.2,129.6,127.6,126.0,125.6,88.1,70.5,68.6,68.2,63.0,44.3,21.8,21.3,21.0,20.9,20.4.ESI(+)-HRMS m/z:calcd for C28H31NO9SNa[M+Na]+580.1612,found 580.1606。
Figure GDA0003463908940000092
Spectral data of 3m white solid,yield 47％,m.p.184-185℃,1H NMR(400MHz,CDCl3)δ7.77(d,J＝8.4Hz,2H),7.35(d,J＝8.0Hz,2H),7.30-7.28(m,1H),7.13(d,J＝8.4Hz,1H),7.05(d,J＝10.0Hz,1H),6.98(d,J＝1.6Hz,1H),6.95-6.9(m,1H),5.62(d,J＝8.4Hz,1H),5.12(t,J＝4.8Hz,1H),4.91(dd,J＝9.2,4.4Hz,1H),4.16(dd,J＝12.0,4.8Hz,1H),3.96-3.89(m,2H),3.60(dd,J＝8.4,5.2Hz,1H),2.44(s,3H),2.09(s,3H),1.97(s,H),1.69(s,3H)；13C NMR(100MHz,CDCl3)δ170.8,169.9,169.4,145.1,136.1,134.7,130.3,129.0,127.6,125.9,125.6,120.2,88.1,70.2,68.7,68.1,62.8,44.1,21.8,20.9,20.8,20.3.ESI(+)-HRMS m/z:calcd for C28H28F3NO9SNa[M+Na]+634.1330,found634.1329。
Figure GDA0003463908940000093
Spectral data of 3o white solid,yield 70％,m.p.140-142℃,1H NMR(600MHz,CDCl3)δ7.76(d,J＝7.8Hz,2H),7.33(d,J＝8.4Hz,2H),7.30(dd,J＝4.8,3.0Hz,1H),7.22(s,1H),7.12(d,J＝5.4Hz,1H),6.87(d,J＝1.8Hz,1H),5.58(d,J＝9.0Hz,1H),5.24(t,J＝4.8Hz,1H),4.88(dd,J＝7.8,4.8Hz,1H),4.17(dd,J＝12.0,4.8Hz,1H),3.99-3.92(m,2H),3.50(dd,J＝8.4,4.8Hz,1H),2.43(s,3H),2.09(s,3H),2.00(s,3H),1.68(s,3H)；13C NMR(150MHz,CDCl3)δ170.9,170.0,169.8,144.8,134.6,133.6,130.2,127.6,126.6,126.3,125.2,120.5,117.9,88.0,70.4,68.5,68.2,63.0,45.0,21.8,21.0,20.9,20.3.ESI(+)-HRMS m/z:calcd for C25H27NNaO9S2[M+Na]+572.1019,found 572.1023。
Figure GDA0003463908940000101
Spectral data of 3r white solid,yield 61％,m.p.124-125℃,1H NMR(400MHz,CDCl3)δ7.39-7.32(m,4H),7.25-7.22(m,1H),6.86(d,J＝2.4Hz,1H),6.05(d,J＝8.8Hz,1H),5.23(dd,J＝3.6,2.4Hz,1H),4.81-4.78(m,1H),4.20-4.18(m,2H),4.06-3.98(m,2H),3.18(s,3H),2.06(s,3H),2.05(s,3H),1.53(s,3H)；13C NMR(150MHz,CDCl3)δ170.4,169.84,169.4,132.3,129.0,127.6,126.4,125.6,120.3,86.8,69.0,68.7,68.3,64.4,44.1,41.9,21.0,20.8,20.1.ESI(+)-HRMS m/z:calcd for C21H25NO9SNa[M+Na]+490.1142,found 490.1127。
Figure GDA0003463908940000102
Spectral data of 3s white solid,yield 57％,m.p.154-155℃,1H NMR(600MHz,CDCl3)δ7.38-7.33(m,,4H),7.23(t,J＝7.2Hz,1H),6.80(d,J＝1.8Hz,1H),6.07(d,J＝9.0Hz,1H),5.24(s,1H),4.79(d,J＝7.8Hz,1H),4.17(d,J＝4.8Hz,2H),4.04-4.0(m,2H),3.46-3.41(m,1H),2.09(s,3H),2.07(s,3H),1.49(s,3H),1.48(d,J＝6.6Hz,6H)；13C NMR(150MHz,CDCl3)δ170.5,169.9,169.5,132.5,129.0,127.8,127.5,125.6,120.1,86.7,68.8,68.7,68.2,64.5,55.7,43.9,21.1,20.8,20.1,17.0,16.1.ESI(+)-HRMS m/z:calcd for C23H29NO9SNa[M+Na]+518.1455,found 518.1443。
Figure GDA0003463908940000111
Spectral data of 3t white solid,yield 70％,m.p.179-180℃,1H NMR(400MHz,CDCl3)δ7.81(d,J＝8.8Hz,2H),7.35-7.29(m,4H),7.24-7.19(m,1H),6.99(d,J＝8.8Hz,2H),6.94(d,J＝1.6Hz,1H),5.60(d,J＝8.4Hz,1H),5.15(t,J＝4.8Hz,1H),4.88(dd,J＝8.0,4.0Hz,1H),4.17(dd,J＝14.4,6.0Hz,1H),4.0-3.95(m,2H),3.87(s,3H),3.64(dd,J＝8.4,4.8Hz,1H),2.09(s,3H),1.94(s,3H),1.62(s,3H)；13C NMR(150MHz,CDCl3)δ170.9,169.9,169.7,163.8,132.4,129.8,129.1,128.9,128.8,127.7,126.9,125.6,121.9,114.8,114.4,88.1,70.6,68.7,68.2,63.0,55.9,44.3,21.0,20.9,20.3.ESI(+)-HRMS m/z:calcd for C27H29NO10SNa[M+Na]+582.1404,found 582.1393。
Figure GDA0003463908940000112
Spectral data of 3u white solid,yield 54％,m.p.67-68℃,1H NMR(600MHz,CDCl3)δ7.83(d,J＝8.4Hz,2H),7.52(d,J＝8.4Hz,2H),7.35-7.31(m,4H),7.24(t,J＝6.6Hz,1H),6.91(s,1H),5.63(d,J＝8.4Hz,1H),5.16(t,J＝4.2Hz,1H),4.87(dd,J＝8.4,4.2Hz,1H),4.18(dd,J＝12.0,5.4Hz,1H),4.02(dd,J＝12.0,3.0Hz,1H),3.99-3.96(m,1H),3.68(dd,J＝7.8,4.8Hz,1H),2.10(s,3H),1.96(s,3H),1.61(s,3H)；13C NMR(150MHz,CDCl3)δ170.8,169.8,169.6,140.4,136.2,132.1,130.0,129.0,129.0,127.9,126.3,125.7,122.6,88.0,70.2,68.8,68.2,63.0,44.2,20.9,20.9,20.3.ESI(+)-HRMS m/z:calcd for C26H26ClNO9SNa[M+Na]+586.0909,found 586.0889。
Figure GDA0003463908940000121
Spectral data of 3v white solid,yield 72％,m.p.174-175℃,1H NMR(600MHz,CDCl3)δ7.90(d,J＝7.8Hz,2H),7.64(t,J＝7.8Hz,1H),7.55(t,J＝7.8Hz,2H),7.35-7.31(m,4H),7.23(t,J＝7.2Hz,1H),6.96(s,1H),5.67(d,J＝9.0Hz,1H),5.16(t,J＝4.2Hz,1H),4.87(dd,J＝8.4,4.2Hz,1H),4.13(dd,J＝12.0,4.8Hz,1H),3.95-3.89(m,2H),3.67(dd,J＝6.0,4.2Hz,1H),2.09(s,3H),1.96(s,3H),1.61(s,3H).13C NMR(150MHz,CDCl3)δ170.8,169.9,169.6,137.9,133.7,129.6,129.0,127.8,127.6,126.7,125.6,122.0,88.0,70.3,68.6,68.2,63.0,44.2,21.0,20.9,20.3.ESI(+)-HRMS m/z:calcd forC26H27NO9SNa[M+Na]+552.1299,found 552.1291。
Figure GDA0003463908940000122
Spectral data of 3w white solid,yield 80％,m.p.159-160℃,1H NMR(400MHz,CDCl3)δ8.04(d,J＝8.0,Hz,1H),7.52(t,J＝7.6,1H),7.39-7.30(m,6H),7.22(t,J＝6.8Hz,1H),7.02(d,J＝1.6Hz,1H),5.85(d,J＝8.8Hz,1H),5.15(t,J＝4.4Hz,1H),4.86(dd,J＝8.0,3.6Hz,1H),4.00(dd,J＝12.0,4.8Hz,1H),3.78(dd,J＝8.8,4.8Hz,1H),3.72-3.68(m,1H),3.56(dd,J＝12.0,3.2Hz,1H),2.69(s,3H),2.05(s,3H),1.94(s,3H),1.62(s,3H)；13C NMR(150MHz,CDCl3)δ170.7,169.8,169.6,138.0,136.9,133.8,132.9,132.4,130.4,128.9,127.6,126.8,126.8,125.6,121.1,88.3,70.8,68.7,68.0,62.6,44.5,20.9,20.8,20.3.ESI(+)-HRMS m/z:calcd for C27H29NO9SNa[M+Na]+566.1455,found 566.1434。
Figure GDA0003463908940000123
Spectral data of 4b white solid,yield 38％,m.p.112-113℃,1H NMR(600MHz,CDCl3)δ8.05(d,J＝7.2Hz,2H),8.03(d,J＝7.8Hz,2H),7.82(d,J＝8.4Hz,2H),7.59(t,J＝7.8Hz,1H),7.50-7.48(m,4H),7.42(t,J＝7.8Hz,2H),7.33(d,J＝8.4Hz,2H),7.29(dd,J＝14.4,7.8Hz,4H),7.26(d,J＝3.6Hz,2H),7.24-7.21(m,1H),7.18(d,J＝9.6Hz,1H),7.14(d,J＝2.4Hz,1H),6.82(t,J＝7.8Hz,1H),5.96(d,J＝9.6Hz,1H),5.72-5.67(m,1H),5.51(d,J＝8.0Hz,1H),4.38(dd,J＝12.0,3.6Hz,1H),4.31(dd,J＝12.0,4.8Hz,1H),4.16-4.13(m,1H),3.96(d,J＝9.0Hz,1H),2.42(s,3H)；13C NMR(150MHz,CDCl3)δ166.3,165.5,165.1,144.7,135.6,133.7,133.4,133.1,132.0,130.3,130.0,129.9,129.8,129.4,129.0,128.7,128.7,128.4,128.2,127.6,127.4,127.3,125.5,120.6,87.0,69.6,69.1,68.6,64.2,44.1,21.7.ESI(+)-HRMS m/z:calcd for C42H35NO9SNa[M+Na]+752.1925,found 752.1910。
Figure GDA0003463908940000131
Spectral data of 4c white solid,yield 60％,m.p.38-39℃,1H NMR(400MHz,CDCl3)δ7.76(d,J＝8.4Hz,2H),7.33(d,J＝4.0Hz,4H),7.30-7.27(m,4H),7.22-7.16(m,8H),7.14-7.10(m,4H),6.85(s,1H),6.78(d,J＝6.8Hz,2H),5.70(d,J＝8.4Hz,1H),4.62(d,J＝4.4Hz,1H),4.59(d,J＝4.8Hz,1H),4.49(d,J＝12.0Hz,1H),4.21(dd,J＝15.2,9.2Hz,3H),3.81(t,J＝4.4Hz,1H),3.76-3.69(m,2H),3.57-3.50(m,2H),3.33(dd,J＝11.2,2.4Hz,1H),2.37(s,3H)；13C NMR(100MHz,CDCl3)δ144.2,138.3,138.0,137.8,135.2,133.2,129.9,128.8,128.5,128.5,128.3,128.2,128.1,128.0,127.9,127.8,127.7,127.6,127.1,126.3,125.7,123.3,89.3,75.8,73.5,72.9,72.8,71.7,69.0,46.1,21.7.ESI(+)-HRMS m/z:calcd for C42H41NO6SNa[M+Na]+710.2547,found 710.2529。
Figure GDA0003463908940000132
Spectral data of 4f white solid,yield 72％,m.p.37-38℃,1H NMR(600MHz,CDCl3)δ7.75(d,J＝7.8Hz,2H),7.34(d,J＝7.8Hz,2H),7.30(d,J＝7.2Hz,4H),7.20(d,J＝7.2Hz,1H),6.87(s,1H),5.37(d,J＝8.4Hz,1H),3.68(d,J＝7.8Hz,1H),3.52(d,J＝10.2Hz,1H),3.39(s,3H),3.38-3.35(m,3H),3.29(d,J＝6.6Hz,1H),3.27(s,3H),3.21(s,3H),2.41(s,3H)；13C NMR(150MHz,CDCl3)δ144.4,134.0,133.1,129.9,128.6,128.0,127.3,125.8,125.7,124.7,90.6,82.9,77.5,72.0,71.1,59.4,59.3,58.9,46.4,21.7.ESI(+)-HRMS m/z:calcd for C24H29NO6SNa[M+Na]+482.1608,found 482.1592。
Figure GDA0003463908940000141
Spectral data of 4g colorless oil,yield 22％,1H NMR(400MHz,CDCl3)δ7.75(d,J＝8.0Hz,2H),7.34(d,J＝7.8Hz,2H),7.30-7.27(m,4H),7.19(t,J＝7.2Hz,1H),6.88(s,1H),5.96-5.89(m,1H),5.72-5.56(m,2H),5.37(d,J＝8.0Hz,1H),5.29(dd,J＝13.2,1.6Hz,1H),5.19(d,J＝10.4Hz,1H),5.12-5.03(m,4H),2.41(s,3H)；13C NMR(150MHz,CDCl3)δ144.4,134.8,134.7,134.6,133.9,133.2,130.0,128.6,128.0,127.3,125.9,125.8,125.0,117.5,117.4,116.9,90.9,81.1,75.6,73.1,72.6,72.5,72.4,68.6,46.7,21.7.ESI(+)-HRMS m/z:calcd for C30H35NO6SNa[M+Na]+560.2077,found 560.2069。
Figure GDA0003463908940000142
Spectral data of 4j white solid,yield 88％,m.p.149-150℃,1H NMR(400MHz,CDCl3)δ7.73(d,J＝8.0Hz,2H),7.34(d,J＝8.0Hz,2H),7.31-7.28(m,3H),7.25(d,J＝6Hz,1H),7.19(t,J＝7.2Hz,1H),6.95(s,1H),5.32(d,J＝2.8Hz,1H),5.15(d,J＝7.2Hz,1H),5.07(dd,J＝9.6,3.2Hz,1H),4.37(t,J＝6.8Hz,1H),4.15-4.06(m,2H),3.22(dd,J＝9.6,7.2Hz,1H),2.43(s,3H),2.14(s,3H),2.09(s,3H),1.64(s,3H)；13C NMR(150MHz,CDCl3)δ170.7,170.3,169.5,144.9,132.5,132.4,130.1,128.5,128.2,127.7,126.4,125.5,125.0,91.8,73.2,69.8,64.9,61.6,40.7,21.8,20.9,20.8,20.4.ESI(+)-HRMS m/z:calcd for C27H29NO9SNa[M+Na]+566.1455,found 566.1431。
Figure GDA0003463908940000143
Spectral data of 4k white solid,yield 51％,m.p.109-110℃,1H NMR(400MHz,CDCl3)δ8.07-8.03(m,4H),7.81(d,J＝8.0Hz,2H),7.60(t,J＝7.6Hz,1H),7.50-7.46(m,4H),7.42(ddd,J＝8.0,4.4,3.2Hz,4H),7.33-7.27(m,6H),7.23(t,J＝8.0Hz,1H),7.16(t,J＝7.6Hz,1H),7.12(d,J＝2.4Hz,1H),5.96(d,J＝9.2Hz,1H),5.75(dd,J＝2.8,2.0Hz,1H),5.50(dt,J＝8.0,1.6Hz,1H),4.41(dd,J＝12.0,3.2Hz,1H),4.33(dd,J＝12.0,5.2Hz,1H),4.20-4.17(m,1H),3.99(d,J＝8.8Hz,1H),2.41(s,3H)；13C NMR(100MHz,CDCl3)δ166.2,165.5,165.2,145.1,134.6,134.5,133.7,133.3,133.2,132.8,130.2,130.1,130.0,129.9,129.7,129.6,129.3,129.0,128.7,128.5,128.3,128.2,127.8,123.5,120.9,114.3,114.1,112.4,112.2,91.8,73.4,70.1,65.7,62.6,41.6,21.8.ESI(+)-HRMSm/z:calcd for C42H35NO9SNa[M+Na]+752.1925,found 752.1913。
Figure GDA0003463908940000151
Spectral data of 4l white solid,yield 54％,m.p.45-46℃,1H NMR(400MHz,CDCl3)δ7.69(d,J＝8.0Hz,2H),7.34-7.14(m,21H),6.89(s,1H),6.80(d,J＝6.8Hz,2H),5.04(d,J＝7.2Hz,1H),4.87(d,J＝11.2Hz,1H),4.58(d,J＝11.6Hz,1H),4.51(d,J＝11.6Hz,1H),4.45-4.38(m,2H),4.15(dd,J＝8.4,5.2Hz,1H),4.07-4.02(m,2H),3.70(t,J＝8.8Hz,1H),3.62-3.55(m,2H),3.31(dd,J＝9.2,6.8Hz,1H),2.37(s,3H)；13C NMR(100MHz,CDCl3)δ144.5,138.6,138.1,137.4,133.6,132.4,129.9,129.1,128.6,128.5,128.4,128.2,128.1,128.1,127.9,127.8,127.7,127.2,127.1,126.2,125.9,125.8,92.6,82.9,74.5,73.6,72.3,72.1,69.7,68.2,42.6,21.7.ESI(+)-HRMS m/z:calcd forC42H41NO6SNa[M+Na]+710.2547,found 710.2525。
Figure GDA0003463908940000152
Spectral data of 4m white solid,yield 42％,m.p.171-173℃,1H NMR(600MHz,CDCl3)δ7.78(d,J＝7.8Hz,2H),7.33(d,J＝7.2Hz,4H),2.29(d,J＝7.2Hz,2H),7.21(t,J＝7.2Hz,1H),6.94(s,1H),5.60(d,J＝8.4Hz,1H),5.12(s,1H),4.61(t,J＝4.2Hz,1H),3.75(t,J＝6.0Hz,1H),3.60(s,1H),2.43(s,3H),1.92(s,3H),1.63(s,3H),1.05(d,J＝6.0Hz,3H)；13C NMR(150MHz,CDCl3)δ169.9,144.5,135.2,132.6,130.0,128.8,127.6,127.5,126.8,125.6,122.1,88.3,73.6,71.1,66.7,44.4,21.7,20.9,20.4,18.8.ESI(+)-HRMS m/z:calcd for C25H27NNaO7S[M+Na]+508.1400,found 508.1410。
以上实施例描述了本发明的基本原理、主要特征及优点，本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。

Claims (2)

1.手性稠环吡喃并二氢吡咯类化合物的制备方法，其特征在于具体步骤为：向装有磁子的烧瓶中加入烯糖类化合物2和催化剂Rh2(TFA)4，再加入溶剂DCE进行溶解，于60～100℃搅拌反应，将1,2,3-三氮唑类化合物1的DCE溶液滴加到上述混合体系中，滴加完毕后继续反应0.5小时，TLC检测反应完毕后减压蒸馏除去溶剂，经硅胶柱色谱分离得到目标产物；
合成过程中的反应方程式如下：
Figure FDA0003463908930000011
对应目标产物的化学式如下：
Figure FDA0003463908930000012
Figure FDA0003463908930000021
2.根据权利要求1所述的手性稠环吡喃并二氢吡咯类化合物的制备方法，其特征在于：所述化合物1、化合物2与催化剂的投料摩尔比为2～3:1:0.02。
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102276673A (zh) * 2011-06-21 2011-12-14 中国科学院成都生物研究所 一种2-脱氧-β-D-吡喃葡萄糖基***类化合物的制备方法
CN106866670A (zh) * 2017-04-28 2017-06-20 遵义医学院 一种螺[3,5`‑吡咯[2,1‑a]异喹啉‑氧化吲哚]类化合物及其制备方法
CN109180653A (zh) * 2018-10-16 2019-01-11 江苏师范大学 一种铜催化制备苯并呋喃-吡咯类化合物的方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102276673A (zh) * 2011-06-21 2011-12-14 中国科学院成都生物研究所 一种2-脱氧-β-D-吡喃葡萄糖基***类化合物的制备方法
CN106866670A (zh) * 2017-04-28 2017-06-20 遵义医学院 一种螺[3,5`‑吡咯[2,1‑a]异喹啉‑氧化吲哚]类化合物及其制备方法
CN109180653A (zh) * 2018-10-16 2019-01-11 江苏师范大学 一种铜催化制备苯并呋喃-吡咯类化合物的方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
C-Branched pyrrolidines from 2-C-acetylmethyl-glycosylazides. Reduction of imines formed by monosaccharide ring opening;Shao Huawu et al.;《Carbohydrate Research》;20061231;第341卷;第2434-2438页 *
Diastereoselective Synthesis of Tetrahydrofurano- and Tetrahy-dropyrano-dihydropyrroles Containing N,O-Acetal Moieties via Rhodium-Catalyzed Transannulation of N-Sulfonyl-1,2,3-triazoles with Oxacycloalkenes;Kim Cheol-Eui et al.;《Advanced Synthesis & Catalysis》;20141127;第357卷;第211页Table 1、第213页Scheme 5、左栏第2段，第217页右栏第5段， *

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