CN104447749B - 一种通过嘌呤对乙烯基环丙烷的选择性开环构建非环核苷的方法 - Google Patents

一种通过嘌呤对乙烯基环丙烷的选择性开环构建非环核苷的方法 Download PDF

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CN104447749B
CN104447749B CN201410673286.XA CN201410673286A CN104447749B CN 104447749 B CN104447749 B CN 104447749B CN 201410673286 A CN201410673286 A CN 201410673286A CN 104447749 B CN104447749 B CN 104447749B
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郭海明
杜聪
谢明胜
王东超
牛红英
渠桂荣
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Abstract

本发明公开了一种通过嘌呤对乙烯基环丙烷的选择性开环构建非环核苷的方法，反应方程式如下：

Description

一种通过嘌呤对乙烯基环丙烷的选择性开环构建非环核苷的方法
技术领域
本发明属于化学与医药技术领域，具体涉及一种通过通过嘌呤对乙烯基环丙烷的选择性开环构建非环核苷的方法。
背景技术
核苷类药物在抗病毒和抗肿瘤化疗药物中具有非常重要的地位，尤其是近十几年来这方面的药物发展速度很快。对天然核苷的结构改造是寻找新的，更加有效地抗病毒药物的重要手段，在目前已上市及处于临床试验阶段的抗病毒药物中，绝大多数都是核苷衍生物，非环核苷衍生物也因此成为最具抗病毒潜能的化合物。但是此类药物还是普遍存在着不良反应多、生物利用度低、易产生耐药性、代谢快等问题。因此对核苷类似物的各个部位进行改性以优化核苷类药物的生物活性具有重要意义。
发明内容
寻求到一种简便、绿色、高效的方法来合成非环核苷类似物，立足于解决此类化合物合成过程中原料昂贵，过程复杂的问题，对核苷类药物的合成及应用提供了参考价值，为新型抗病毒及抗肿瘤药物的研究提供了原料。
为了实现本发明的目的，本发明采用以下技术方案：一种通过嘌呤对乙烯基环丙烷的选择性开环构建非环核苷的方法，反应方程式如下：
其中：R1选自下列基团中的一种：F、Cl、Br、I、H、甲氧基、乙氧基、哌啶、吗啉、
二甲胺基、丙硫基、苯基、萘基；
R2选自下列基团中的一种：H、NH2、Cl、F；
R3选自下列基团中的一种：甲基、乙基、异丙基、叔丁基、苄基。
本发明的进一步改进包括：
所述反应方程中两个X相同。
所述反应方程中两个X不同，虚线表示的键为单键或者双键，并且虚线所在的环为芳环。
所述的方法具体为：(a)以二恶烷作溶剂，氮气保护下以加入Pd2(dba)3·CHCl3和配体L，然后依次加入两种反应物，30摄氏度反应18小时；
其中：配体L的结构式为：(b)以二恶烷作溶剂，氮气保护下以加入AlCl3，然后依次加入两种反应物，85摄氏度反应18小时；(c)以二恶烷作溶剂，氮气保护下以加入MgI2，然后依次加入两种反应物，85摄氏度反应18小时。
所述的非环核苷及其类似物选自下列38个具体化合物中的一个：
本发明通过使用特定的催化剂，则能以高产率和高化学选择性得到目标产物。该反应具有操作简单、反应条件温和、催化剂便宜易得等几个优点，为合成非环核苷类似物提供了一条简洁实用的合成方法。
具体实施方式
本发明为非环核苷及其类似物的合成提供了一种具有优秀化学选择性和高产率的方法，其特征在于反应方程式如下：
其中：R1选自下列基团中的一种：F、Cl、Br、I、H、甲氧基、乙氧基、哌啶、吗啉、二甲胺基、丙硫基、苯基、萘基；
R2选自下列基团中的一种：H、NH2、Cl、F；
R3选自下列基团中的一种：甲基、乙基、异丙基、叔丁基、苄基。
两个X可以相同，也可以不同，虚线表示的键为单键或者双键，并且虚线所在的环为芳环。
在本发明的一个优选实施方式中，所述的手性环核苷及其类似物选自38个具体化合物中的一个。
在本发明的一个优选实施方式中，所述的方法具体反应条件为：
(a)取一休朗克反应管，氮气保护下加入5mol％的Pd2(dba)3·CHCl3和10mol％的配体L，2-乙烯基环丙烷-1,1-二羧酸二乙酯(0.1mmol)、6-氯嘌呤(0.15mmol)，以重蒸的二恶烷作溶剂，30摄氏度反应18小时；通过薄层板检测(TLC)；经过柱层析得到目标产物，收率82％。
其中：配体L的结构式为：
(b)取一休朗克反应管，氮气保护下加入AlCl3(0.1mmol)，2-乙烯基环丙烷-1,1-二羧酸二乙酯(0.3mmol)、6-氯嘌呤(0.1mmol)，以重蒸的二恶烷作溶剂，85摄氏度反应18小时；通过薄层板检测(TLC)；经过柱层析得到目标产物，收率79％；
(c)取一休朗克反应管，氮气保护下加入10mol％MgI2，2-乙烯基环丙烷-1,1-二羧酸二乙酯(0.5mmol)、6-氯嘌呤(0.1mmol)，以重蒸的二恶烷作溶剂，85摄氏度反应18小时；通过薄层板检测(TLC)；经过柱层析得到目标产物，收率72％。
(E)-dimethyl2-(4-(6-chloro-9H-purin-9-yl)but-2-en-1-yl)malonate(3a)
1HNMR(400MHz,CDCl3):δ8.75(s,1H),8.12(s,1H),5.87-5.75(m,2H),4.84(d,J＝5.2Hz,2H),3.72(s,6H),3.47(t,J＝7.2Hz,1H),2.69(t,J＝6.4Hz,2H)ppm.13CNMR(100MHz,CDCl3):δ168.8,151.9,151.5,151.0,144.7,132.6,131.5,125.8,52.6,50.8,45.5,31.2ppm.HRMS:calcdforC14H15ClN4O4Na[M+Na]+361.0674,found361.0677.
(E)-diethyl2-(4-(6-chloro-9H-purin-9-yl)but-2-en-1-yl)malonate(3b)
1HNMR(400MHz,CDCl3):δ8.75(s,1H),8.12(s,1H),5.88-5.75(m,2H),4.84(d,J＝5.2Hz,2H),4.21-4.14(m,4H),3.42(t,J＝7.2Hz,1H),2.68(t,J＝6.4Hz,2H),1.24(t,J＝6.8Hz,6H)ppm.13CNMR(100MHz,CDCl3):δ168.3,151.7,151.4,150.7,144.7,132.7,131.3,125.5,61.4,51.0,45.4,31.0,13.9ppm.HRMS:calcdforC16H19ClN4O4Na[M+Na]+389.0987,found389.0987.
(E)-diisopropyl2-(4-(6-chloro-9H-purin-9-yl)but-2-en-1-yl)malonate(3c)
1HNMR(400MHz,CDCl3):δ8.75(s,1H),8.12(s,1H),5.88-5.74(m,2H),5.07-4.98(m,2H),4.83(d,J＝5.6Hz,2H),3.34(t,J＝7.2Hz,1H),2.65(t,J＝6.4Hz,2H),1.21(t,J＝3.2Hz,12H)ppm.13CNMR(100MHz,CDCl3):δ168.0,152.0,151.6,151.0,144.8,133.1,131.6,125.4,69.2,51.5,45.6,31.1,21.6,21.5ppm.HRMS:calcdforC18H23ClN4O4Na[M+Na]+417.1300,found417.1301.
(E)-di-tert-butyl2-(4-(6-chloro-9H-purin-9-yl)but-2-en-1-yl)malonate(3d)
1HNMR(400MHz,CDCl3):δ8.75(s,1H),8.13(s,1H),5.87-5.74(m,2H),4.84(d,J＝5.2Hz,2H),3.22(t,J＝7.2Hz,1H),2.59(t,J＝6.4Hz,2H),1.42(s,18H)ppm.13CNMR(100MHz,CDCl3):δ167.9,152.0,151.0,144.8,133.4,125.0,81.8,53.1,45.7,31.2,27.9ppm.HRMS:calcdforC20H27ClN4O4Na[M+Na]+445.1613,found445.1606.
(E)-bis(2,2,2-trifluoroethyl)2-(4-(6-chloro-9H-purin-9-yl)but-2-en-1-yl)malonate(3e)
1HNMR(400MHz,CDCl3):δ8.75(s,1H),8.09(s,1H),5.88–5.72(m,2H),4.85(d,J＝5.6Hz,2H),4.53(q,J＝8.0Hz,4H),3.67(t,J＝7.2Hz,1H),2.76(t,J＝6.8Hz,2H)ppm.13CNMR(100MHz,CDCl3):δ166.1,152.1,151.2,144.7,130.6,127.2,61.3,60.9,50.3,45.4,31.0ppm.HRMS:calcdforC16H13ClF6N4O4Na[M+Na]+497.0422,found497.0412.
(E)-dimethyl2-(4-(6-iodo-9H-purin-9-yl)but-2-en-1-yl)malonate(3f)
1HNMR(400MHz,CDCl3):δ8.63(s,1H),8.12(s,1H),5.80(q,J＝5.3Hz,2H),4.81(d,J＝4.6Hz,2H),3.72(s,6H),3.46(t,J＝7.2Hz,1H),2.68(t,J＝6.2Hz,2H)ppm.13CNMR(100MHz,CDCl3):δ168.9,152.0,147.8,144.1,138.6,132.6,125.8,122.1,52.7,50.9,45.6,31.2ppm.HRMS:calcdforC14H15IN4O4Na[M+Na]+453.0030,found453.0032.
(E)-diethyl2-(4-(6-(propylthio)-9H-purin-9-yl)but-2-en-1-yl)malonate(3g)
1HNMR(400MHz,CDCl3):δ8.69(s,1H),7.91(s,1H),5.81-5.71(m,2H),4.77(d,J＝4.4Hz,2H),4.22-4.10(m,4H),3.41-3.34(m,3H),2.66(t,J＝6.4Hz,2H),1.86-1.77(m,2H),1.22(t,J＝7.2Hz,6H),1.07(t,J＝7.2Hz,3H)ppm.13CNMR(100MHz,CDCl3):δ168.5,161.6,151.9,148.1,142.0,131.9,131.3,126.3,61.6,51.3,45.0,31.2,30.6,22.9,14.0,13.4ppm.HRMS:calcdforC19H26N4O4SNa[M+Na]+429.1567,found429.1569.
(E)-diethyl2-(4-(2-chloro-6-(pyrrolidin-1-yl)-9H-purin-9-yl)but-2-en-1-yl)malonate(3h)
1HNMR(400MHz,CDCl3):δ7.63(s,1H),5.77–5.69(m,2H),4.68(s,2H),4.17–4.16(m,6H),3.74(s,2H),3.39(t,J＝7.2Hz,1H),2.64(t,J＝6.4Hz,2H),2.06-1.97(m,4H),1.23(t,J＝7.2Hz,6H)ppm.13CNMR(100MHz,CDCl3):δ168.6,154.2,153.3,151.1,138.6,131.4,126.7,119.0,61.5,51.4,48.9,47.7,44.8,31.2,26.1,24.1,14.0ppm.HRMS:calcdforC20H26ClN5O4Na[M+Na]+458.1566,found458.1563.
(E)-diethyl2-(4-(2-chloro-6-(piperidin-1-yl)-9H-purin-9-yl)but-2-en-1-yl)malonate(3i)
1HNMR(400MHz,CDCl3):δ7.63(s,1H),5.78-5.66(m,2H),4.66(d,J＝4.8Hz,2H),4.23-4.141(m,4H),3.39(t,J＝7.2Hz,1H),2.65(t,J＝6.4Hz,2H),1.70(s,6H),1.23(t,J＝7.2Hz,6H)ppm.13CNMR(100MHz,CDCl3):δ168.6,154.0,153.9,151.8,137.8,131.4,126.6,118.5,61.5,51.3,44.8,31.2,26.1,24.6,14.0ppm.HRMS:calcdforC21H28ClN5O4Na[M+Na]+472.1722,found472.1728.
(E)-diethyl2-(4-(2-chloro-6-morpholino-9H-purin-9-yl)but-2-en-1-yl)malonate(3j)
1HNMR(400MHz,CDCl3):δ7.66(s,1H),5.73(dd,J＝7.6,5.0Hz,2H),4.68(d,J＝4.3Hz,2H),4.22-4.15(m,8H),3.82(t,J＝4.8Hz,4H),3.40(t,J＝7.2Hz,1H),2.70–2.60(m,2H),1.24(t,J＝7.2Hz,6H)ppm.13CNMR(100MHz,CDCl3):δ168.6,154.0,153.9,152.0,138.4,131.7,126.5,118.7,66.9,61.6,51.4,44.9,31.2,14.1ppm.HRMS:calcdforC20H26ClN5O5Na[M+Na]+474.1515,found474.1518.
(E)-dimethyl2-(4-(6-phenyl-9H-purin-9-yl)but-2-en-1-yl)malonate(3k)
1HNMR(400MHz,CDCl3):δ9.02(s,1H),8.77(d,J＝7.6Hz,2H),8.10(s,1H),7.60–7.51(m,3H),5.87–5.75(m,2H),4.86(d,J＝4.4Hz,2H),3.71(s,6H),3.47(t,J＝7.2Hz,1H),2.69(t,J＝6.4Hz,2H)ppm.13CNMR(100MHz,CDCl3):δ168.9,154.9,152.4,152.2,143.9,135.6,131.8,131.0,131.0,129.7,128.6,126.5,52.7,51.0,45.0,31.3ppm.HRMS:calcdforC20H20N4O4Na[M+Na]+403.1377,found403.1371.
(E)-diethyl2-(4-(6-(phenanthren-9-yl)-9H-purin-9-yl)but-2-en-1-yl)malonate(3l)
1HNMR(400MHz,CDCl3):δ9.17(s,1H),8.77(dd,J＝19.6,8.4Hz,2H),8.27(s,1H),8.22(d,J＝8.0Hz,1H),8.11(s,1H),7.98(d,J＝7.6Hz,1H),7.75-7.55(m,4H),5.92-5.83(m,2H),4.92(d,J＝3.2Hz,2H),4.23-4.14(m,4H),3.45(t,J＝7.2Hz,1H),2.71(t,J＝5.6Hz,2H),1.24(t,J＝7.2Hz,6H)ppm.13CNMR(100MHz,CDCl3):δ168.5,158.0,152.3,151.9,144.4,132.9,132.3,131.3,131.3,131.1,130.9,129.6,129.6,128.5,127.7,126.8,126.8,126.7,126.5,126.2,122.9,122.6,61.6,51.3,45.2,31.2,14.1ppm.HRMS:calcdforC30H28N4O4Na[M+Na]+531.2003,found531.2002.
(E)-diethyl2-(4-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)but-2-en-1-yl)malonate(3m)
1HNMR(400MHz,CDCl3):δ7.53(s,1H),5.84-5.73(m,2H),4.87(d,J＝4.0Hz,2H),4.21-4.13(m,4H),3.58(s,3H),3.42-3.38(m,4H),2.66(t,J＝6.4Hz,2H),1.24(t,J＝7.2Hz,6H)ppm.13CNMR(100MHz,CDCl3):δ168.6,155.2,151.7,148.8,140.5,132.2,126.8,106.8,61.6,51.3,48.3,31.2,29.8,28.0,14.1ppm.HRMS:calcdforC18H24N4O6Na[M+Na+]415.1588,found415.1587.
(E)-dimethyl2-(4-(2-chloro-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)malonate(3n)
1HNMR(400MHz,CDCl3):δ7.71–7.69(m,1H),7.30–7.26(m,3H),5.71–5.56(m,2H),4.76(d,J＝5.2Hz,2H),3.66(s,6H),3.41(t,J＝7.2Hz,1H),2.64(t,J＝7.2Hz,2H)ppm.13CNMR(100MHz,CDCl3):δ168.9,141.7,140.3,134.8,130.2,126.1,123.2,122.7,119.5,109.6,52.5,51.1,45.8,31.2ppm.HRMS:calcdforC16H17ClN2O4Na[M+Na]+359.0769,found359.0763.
(E)-diethyl2-(4-(4-nitro-1H-imidazol-1-yl)but-2-en-1-yl)malonate(3o)
1HNMR(400MHz,CDCl3):δ8.00(s,1H),7.58(s,1H),5.79-5.68(m,2H),4.91(d,J＝4.4Hz,2H),4.22-4.14(m,4H),3.39(t,J＝6.4Hz,1H),2.65(t,J＝7.2Hz,2H),1.25(t,J＝7.2Hz,6H)ppm.13CNMR(100MHz,CDCl3):δ168.5,140.7,133.5,132.7,125.9,61.6,51.2,49.4,31.1,14.0ppm.HRMS:calcdforC14H19N3O6Na[M+Na]+348.1166,found348.1174.
dimethyl2-(2-(6-chloro-9H-purin-9-yl)but-3-en-1-yl)malonate(5a)
1HNMR(400MHz,CDCl3):δ8.74(s,1H),8.12(s,1H),6.23-6.14(m,1H),5.38(d,J＝10.4Hz,1H),5.32-5.28(m,2H),3.73(s,3H),3.63(s,3H),3.24(t,J＝7.2Hz,1H),2.75(t,J＝7.6Hz,2H)ppm.13CNMR(100MHz,CDCl3):δ168.5,168.5,151.9,151.5,151.2,143.8,134.0,131.7,119.8,56.5,52.9,52.9,48.3,32.8ppm.HRMS:calcdforC14H16ClN4O4Na[M+Na]+361.0674,found361.0664.
diethyl2-(2-(6-chloro-9H-purin-9-yl)but-3-en-1-yl)malonate(5b)
1HNMR(400MHz,CDCl3):δ8.74(s,1H),8.12(s,1H),6.23-6.22(m,1H),5.38(d,J＝10.4Hz,1H),5.32-5.28(m,2H),4.23–4.03(m,4H),3.20(t,J＝7.4Hz,1H),2.73(t,J＝8.0Hz,2H),1.26-1.17(m,6H)ppm.13CNMR(100MHz,CDCl3):δ168.1,168.1,151.8,151.5,151.0,143.8,134.1,131.6,119.6,61.9,61.8,56.5,48.6,32.6,13.9,13.8ppm.HRMS:calcdforC16H19ClN4O4Na[M+Na]+389.0987,found389.0978.
diisopropyl2-(2-(6-chloro-9H-purin-9-yl)but-3-en-1-yl)malonate(5c)
1HNMR(400MHz,CDCl3):δ8.73(s,1H),8.13(s,1H),6.23-6.14(m,1H),5.37(dd,J＝10.4,0.7Hz,1H),5.31–5.27(m,2H),5.10-5.00(m,1H),4.98-4.89(m,1H),3.11(t,J＝7.2Hz,1H),2.70(t,J＝7.2Hz,2H),1.24–1.14(m,12H)ppm.13CNMR(100MHz,CDCl3):δ167.8,167.7,151.9,151.5,151.2,143.8,134.2,131.7,119.7,69.7,69.6,56.6,49.0,32.6,21.6,21.5,21.5,21.4ppm.HRMS:calcdforC18H23ClN4O4Na[M+Na]+417.1300,found417.1292.
di-tert-butyl2-(2-(6-chloro-9H-purin-9-yl)but-3-en-1-yl)malonate(5d)
1HNMR(400MHz,CDCl3):δ8.74(s,1H),8.13(s,1H),6.23–6.14(m,1H),5.36(d,J＝10.0Hz,1H),5.30–5.26(m,2H),2.99(t,J＝7.2Hz,1H),2.62(t,J＝7.6Hz,2H),1.45(s,9H),1.39(s,9H)ppm.13CNMR(100MHz,CDCl3):δ167.6,167.5,151.9,151.6,151.2,143.8,134.4,131.8,119.5,82.4,82.4,56.6,50.5,32.8,27.8,27.8ppm.HRMS:calcdforC20H27ClN4O4Na[M+Na]+445.1613,found445.1605.
dimethyl2-(2-(6-iodo-9H-purin-9-yl)but-3-en-1-yl)malonate(5e)
1HNMR(400MHz,CDCl3):δ8.62(s,1H),8.12(s,1H),6.22–6.14(m,1H),5.39–5.24(m,3H),3.73(s,3H),3.63(s,3H),3.23(t,J＝7.4Hz,1H),2.74(t,J＝7.4Hz,2H)ppm.13CNMR(100MHz,CDCl3):δ168.6,168.5,152.0,147.8,143.1,138.7,134.0,122.4,119.8,56.6,53.0,52.9,48.3,32.8ppm.HRMS:calcdforC14H15IN4O4Na[M+Na]+453.0030,found453.0029.
diethyl2-(2-(6-ethoxy-9H-purin-9-yl)but-3-en-1-yl)malonate(5f)
1HNMR(400MHz,CDCl3):δ8.50(s,1H),7.90(s,1H),6.22-6.13(m,1H),5.33–5.21(m,3H),4.66(q,J＝7.2Hz,2H),4.22–4.03(m,4H),3.17(t,J＝7.2Hz,1H),2.70(t,J＝7.4Hz,2H),1.51(t,J＝7.2Hz,3H),1.21(dt,J＝19.9,7.1Hz,6H)ppm.13CNMR(100MHz,CDCl3):δ168.4,168.3,160.9,152.1,151.8,140.6,134.8,121.6,118.8,63.1,61.9,61.9,55.8,48.6,32.9,14.5,14.0,13.9ppm.HRMS:calcdforC18H24N4O5Na[M+Na]+399.1639,found399.1642.
diethyl2-(2-(2-chloro-6-(piperidin-1-yl)-9H-purin-9-yl)but-3-en-1-yl)malonate(5g)
1HNMR(400MHz,CDCl3):δ7.66(s,1H),6.15-6.06(m,1H),5.32-5.21(m,2H),
5.19-5.15(m,1H),4.28–4.01(m,8H),3.16(dd,J＝8.0,6.4Hz,1H),2.70–2.51(m,2H),1.72–1.69(m,6H),1.26(t,J＝7.4Hz,3H),1.19(t,J＝7.4Hz,3H)ppm.13CNMR(100MHz,CDCl3):δ168.4,168.3,154.0,153.8,151.9,136.5,135.0,118.5,61.9,61.8,54.7,48.6,33.1,26.1,24.6,13.9,13.9ppm.HRMS:calcdforC21H28ClN5O4Na[M+Na+]472.1722,found472.1713.
diethyl2-(2-(6-cyclopentyl-9H-purin-9-yl)but-3-en-1-yl)malonate(5h)
1HNMR(400MHz,CDCl3):δ8.87(s,1H),8.00(s,1H),6.24–6.15(m,1H),5.35–5.25(m,3H),4.22–4.14(m,2H),4.11–3.99(m,2H),3.93-3.84(m,1H),3.22(t,J＝7.2Hz,1H),2.79–2.67(m,2H),2.17–1.76(m,8H),1.23(t,J＝7.2Hz,3H),1.16(t,J＝7.2Hz,3H)ppm.13CNMR(100MHz,CDCl3):δ168.4,168.3,166.4,152.5,150.4,142.0,134.8,132.3,119.0,61.9,61.8,55.7,48.8,42.6,32.8,32.8,26.3,14.0,13.9ppm.HRMS:calcdforC21H28N4O4Na[M+Na]+423.2003,found423.1996.
diethyl2-(2-(6-(phenanthren-9-yl)-9H-purin-9-yl)but-3-en-1-yl)malonate(5i)
1HNMR(400MHz,CDCl3):δ9.16(s,1H),8.77(dd,J＝20.0,8.0Hz,2H),8.29–8.25(m,2H),8.12(s,1H),7.99(d,J＝7.6Hz,1H),7.73–7.56(m,4H),6.32-6.24(m,1H),5.44–5.35(m,3H),4.27–4.07(m,4H),3.33(t,J＝7.2Hz,1H),2.88–2.76(m,2H),1.29–1.20(m,6H)ppm.13CNMR(100MHz,CDCl3):δ168.4,168.3,158.2,152.3,151.9,143.3,143.3,134.6,132.9,131.3,131.2,131.2,131.0,131.0,129.6,127.8,126.8,126.8,126.7,126.5,122.9,122.6,119.4,62.0,61.9,56.0,48.8,32.8,14.0,14.0ppm.HRMS:calcdforC30H29N4O4[M+H]+509.2183,found509.2174.
diethyl2-(2-(1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate(5j)
1HNMR(400MHz,CDCl3):δ7.93(s,1H),7.83–7.80(m,1H),7.42-7.40(m,1H),7.31–7.28(m,2H),6.12–6.04(m,1H),5.35(dd,J＝10.4,1.2Hz,1H),5.23(dd,J＝17.2,1.2Hz,1H),5.06–5.01(m,1H),4.21–4.03(m,4H),3.18(dd,J＝8.0,6.4Hz,1H),2.73–2.59(m,2H),1.24-1.18(m,6H)ppm.13CNMR(100MHz,CDCl3):δ168.6,168.4,144.0,141.4,135.0,133.1,123.0,122.4,120.6,118.7,110.5,61.9,61.8,56.1,48.5,32.6,14.0,13.9ppm.HRMS:calcdforC18H22N2O4Na[M+Na]+353.1472,found353.1467.
diethyl2-(2-(5,6-dimethyl-1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate(5k)
1HNMR(400MHz,CDCl3):δ7.79(s,1H),7.55(s,1H),7.13(s,1H),6.09-6.01(m,1H),5.30(dd,J＝10.4,1.2Hz,1H),5.18(dd,J＝17.2,1.2Hz,1H),4.98–4.93(m,1H),4.21–4.05(m,4H),3.16-3.13(m,1H),2.69–2.56(m,2H),2.36-2.35(m,6H),1.23-1.16(m,6H)ppm.13CNMR(100MHz,CDCl3):δ168.5,168.3,142.4,140.6,135.1,132.0,131.4,131.3,120.3,118.2,110.5,61.7,61.7,55.9,48.4,32.4,20.5,20.1,13.8,13.8ppm.HRMS:calcdforC20H27N2O4[M+H+]359.1965,found359.1957
diethyl2-(2-(1H-benzo[d][1,2,3]triazol-1-yl)but-3-en-1-yl)malonate(5l)
1HNMR(400MHz,CDCl3):δ8.06(d,J＝8.4Hz,1H),7.52-7.44(m,2H),7.39-7.35(m,1H),6.22-6.14(m,1H),5.50-5.44(m,1H),5.32(d,J＝10.4Hz,1H),5.23(dd,J＝16.8,0.8Hz,1H),4.20–4.03(m,4H),3.22(dd,J＝8.4,6.4Hz,1H),2.96-2.88(m,1H),2.80-2.73(m,1H),1.22-1.17(m,6H)ppm.13CNMR(100MHz,CDCl3):δ168.6,168.4,146.1,134.8,132.5,127.3,124.1,120.1,118.9,109.7,61.7,61.7,59.7,48.4,32.4,13.9ppm.HRMS:calcdforC17H21N3O4Na[M+Na]+354.1424,found354.1419.
dimethyl2-(2-(6-chloro-7H-purin-7-yl)but-3-en-1-yl)malonate(6a)
1HNMR(400MHz,CDCl3):δ8.93(s,1H),8.36(s,1H),6.13-6.05(m,1H),5.76(d,J＝7.6Hz,1H),5.44(dd,J＝10.4,1.2Hz,1H),5.25(dd,J＝17.2,1.2Hz,1H),3.75(s,3H),3.68(s,3H),3.38(t,J＝7.2Hz,1H),2.78-2.67(m,2H)ppm.13CNMR(100MHz,CDCl3):δ168.4,168.3,161.6,152.5,146.8,142.8,134.7,122.1,120.0,57.3,53.1,53.0,48.2,33.7ppm.HRMS:calcdforC14H15ClN4O4Na[M+Na]+361.0674,found361.0668.
diethyl2-(2-(6-chloro-7H-purin-7-yl)but-3-en-1-yl)malonate(6b)
1HNMR(400MHz,CDCl3):δ8.90(s,1H),8.35(s,1H),6.12–6.03(m,1H),5.74(q,J＝7.2Hz,1H),5.41(d,J＝10.4Hz,1H),5.22(d,J＝17.2Hz,1H),4.23–4.05(m,4H),3.31(t,J＝7.2Hz,1H),2.77–2.68(m,2H),1.25–1.19(m,6H)ppm.13CNMR(100MHz,CDCl3):δ168.0,167.9,161.6,152.3,146.9,142.7,134.8,122.1,119.8,62.1,62.0,57.3,48.5,33.5,13.8ppm.HRMS:calcdforC16H19ClN4O4Na[M+Na]+389.0987,found389.0978.
diisopropyl2-(2-(6-chloro-7H-purin-7-yl)but-3-en-1-yl)malonate(6c)
1HNMR(400MHz,CDCl3):δ8.90(s,1H),8.36(s,1H),6.11-6.03(m,1H),5.76-5.07(m,1H),5.40(dd,J＝10.4,1.2Hz,1H),5.20(dd,J＝16.8,1.2Hz,1H),5.07–4.91(m,2H),3.24(t,J＝7.2Hz,1H),2.76–2.63(m,2H),1.22-1.15(m,12H)ppm.13CNMR(100MHz,CDCl3):δ167.6,161.7,152.5,146.9,142.8,135.0,122.2,119.7,69.9,69.9,57.5,48.9,33.4,21.5,21.5,21.4ppm.HRMS:calcdforC18H23ClN4O4Na[M+Na]+417.1300,found417.1290.
di-tert-butyl2-(2-(6-chloro-7H-purin-7-yl)but-3-en-1-yl)malonate(6d)
1HNMR(400MHz,CDCl3):δ8.90(s,1H),8.36(s,1H),6.10–6.01(m,1H),5.70(q,J＝7.2Hz,1H),5.38(dd,J＝10.4,0.8Hz,1H),5.17(dd,J＝17.2,0.8Hz,1H),3.15(t,J＝7.2Hz,1H),2.68-2.59(m,2H),1.44(s,3H),1.40(s,3H)ppm.13CNMR(100MHz,CDCl3):δ167.5,167.4,161.7,152.4,146.9,142.9,135.3,122.3,119.5,82.7,57.7,50.5,33.4,27.9,27.8ppm.HRMS:calcdforC20H27ClN4O4Na[M+Na]+445.1613,found445.1606.
dimethyl2-(2-(6-iodo-7H-purin-7-yl)but-3-en-1-yl)malonate(6e)
1HNMR(400MHz,CDCl3):δ8.77(s,1H),8.37(s,1H),6.09-6.03(m,2H),5.40(d,J＝9.2Hz,1H),5.16(d,J＝15.6Hz,1H),3.75(s,3H),3.65(s,3H),3.39(t,J＝7.2Hz,1H),2.83–2.71(m,2H)ppm.13CNMR(100MHz,CDCl3):δ168.4,168.4,159.0,152.7,146.9,135.0,127.6,119.6,108.3,55.0,53.2,53.1,48.2,33.5ppm.HRMS:calcdforC14H15IN4O4Na[M+Na]+453.0030,found453.0023.
dimethyl2-(2-(2,6-dichloro-7H-purin-7-yl)but-3-en-1-yl)malonate(6f)
1HNMR(400MHz,CDCl3):δ8.35(s,1H),6.10–6.01(m,1H),5.68(q,J＝6.8Hz,1H),5.44(dd,J＝9.2,1.2Hz,1H),5.23(dd,J＝15.6,1.2Hz,1H),3.73(s,3H),3.68(s,3H),3.35(t,J＝7.2Hz,1H),2.74–2.69(m,2H)ppm.13CNMR(100MHz,CDCl3):δ168.3,168.3,163.3,153.3,148.1,143.6,134.4,121.4,120.3,57.6,53.2,53.1,48.1,33.6ppm.HRMS:calcdforC14H14Cl2N4O4Na[M+Na]+395.0284,found395.0277.diethyl2-(2-(1H-benzo[d][1,2,3]triazol-1-yl)but-3-en-1-yl)malonate(6g)
1HNMR(400MHz,CDCl3):δ8.06(d,J＝8.4Hz,1H),7.52-7.44(m,2H),7.39-7.35(m,1H),6.22-6.14(m,1H),5.50-5.44(m,1H),5.32(d,J＝10.4Hz,1H),5.23(dd,J＝16.8,0.8Hz,1H),4.20–4.03(m,4H),3.22(dd,J＝8.4,6.4Hz,1H),2.96-2.88(m,1H),2.80-2.73(m,1H),1.22-1.17(m,6H)ppm.13CNMR(100MHz,CDCl3):δ168.6,168.4,146.1,134.8,132.5,127.3,124.1,120.1,118.9,109.7,61.7,61.7,59.7,48.4,32.4,13.9ppm.HRMS:calcdforC17H21N3O4Na[M+Na]+354.1424,found354.1419.
diethyl2-(2-(1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate(6h)
1HNMR(400MHz,CDCl3):δ7.93(s,1H),7.83–7.80(m,1H),7.42-7.40(m,1H),7.31–7.28(m,2H),6.12–6.04(m,1H),5.35(dd,J＝10.4,1.2Hz,1H),5.23(dd,J＝17.2,1.2Hz,1H),5.06–5.01(m,1H),4.21–4.03(m,4H),3.18(dd,J＝8.0,6.4Hz,1H),2.73–2.59(m,2H),1.24-1.18(m,6H)ppm.13CNMR(100MHz,CDCl3):δ168.6,168.4,144.0,141.4,135.0,133.1,123.0,122.4,120.6,118.7,110.5,61.9,61.8,56.1,48.5,32.6,14.0,13.9ppm.HRMS:calcdforC18H22N2O4Na[M+Na]+353.1472,found353.1467.
diethyl2-(2-(2-methyl-1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate(6i)
1HNMR(400MHz,CDCl3):δ7.70-7.67(m,1H),7.35-7.33(m,1H),7.23–7.16(m,2H),6.14-6.06(m,1H),5.29(dd,J＝10.4,1.2Hz,1H),5.13–5.06(m,2H),4.23–4.06(m,2H),3.98(q,J＝7.2Hz,2H),3.12-3.01(m,1H),2.84-2.76(m,1H),2.72–2.64(m,1H),2.57(s,3H),1.20(t,J＝7.2Hz,3H),1.13(t,J＝7.2Hz,3H)ppm.13CNMR(100MHz,CDCl3):δ168.6,168.3,151.6,142.7,1346,133.5,122.1,122.0,119.3,118.0,111.1,61.8,61.8,55.6,48.5,31.2,14.6,13.9,13.8ppm.HRMS:calcdforC19H25N2O4[M+H+]345.1809,found345.1800.
diethyl2-(2-(5,6-dimethyl-1H-benzo[d]imidazol-1-yl)but-3-en-1-yl)malonate(6j)
1HNMR(400MHz,CDCl3):δ7.79(s,1H),7.55(s,1H),7.13(s,1H),6.09-6.01(m,1H),5.30(dd,J＝10.4,1.2Hz,1H),5.18(dd,J＝17.2,1.2Hz,1H),4.98–4.93(m,1H),4.21–4.05(m,4H),3.16-3.13(m,1H),2.69–2.56(m,2H),2.36-2.35(m,6H),1.23-1.16(m,6H)ppm.13CNMR(100MHz,CDCl3):δ168.5,168.3,142.4,140.6,135.1,132.0,131.4,131.3,120.3,118.2,110.5,61.7,61.7,55.9,48.4,32.4,20.5,20.1,13.8,13.8ppm.HRMS:calcdforC20H27N2O4[M+H+]359.1965,found359.1957.
diethyl2-(2-(4-nitro-1H-imidazol-1-yl)but-3-en-1-yl)malonate(6k)
1HNMR(400MHz,CDCl3):δ7.79(s,1H),7.48(s,1H),5.99-5.91(m,1H),5.44(d,J＝10.4Hz,1H),5.30(d,J＝17.2Hz,1H),4.83-4.77(m,1H),4.23–4.17(m,4H),3.21(t,J＝7.2Hz,1H),2.53-2.48(m,2H),1.29-1.25(m,6H)ppm.13CNMR(100MHz,CDCl3):δ168.1,168.0,135.1,134.1,120.4,117.6,62.2,62.2,59.1,48.2,33.4,14.0,14.0ppm.HRMS:calcdforC14H219N3O6Na[M+Na+]348.1166,found348.1165.
按照本发明方法，共合成出38个化合物，具体如下:
以上显示和描述了本发明的基本原理和主要特征和本发明的优点。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，在不脱离本发明精神和范围的前提下，本发明还会有各种变化和改进，这些变化和改进都落入要求保护的本发明范围内。本发明要求保护范围由所附的权利要求书及其等效物界定。

Claims (2)

1.一种对乙烯基环丙烷的选择性开环构建非环核苷的方法，其特征在于，反应方程式如下：
其中：R1选自下列基团中的一种：F、Cl、Br、I、H、甲氧基、乙氧基、哌啶、吗啉、二甲胺基、丙硫基、苯基、萘基；
R2选自下列基团中的一种：H、NH2、Cl、F；
所述的方法具体为：
(a)以二噁烷作溶剂，氮气保护下以加入Pd2(dba)3·CHCl3和配体L，然后依次加入两种反应物，30摄氏度反应18小时；
其中：配体L的结构式为：
(b)以二噁烷作溶剂，氮气保护下以加入AlCl3，然后依次加入两种反应物，85摄氏度反应18小时；
(c)以二噁烷作溶剂，氮气保护下以加入MgI2，然后依次加入两种反应物，85摄氏度反应18小时。
2.根据权利要求1所述的方法，其特征在于，所述反应方程中两个X相同。
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0502690A2 (en) * 1991-03-05 1992-09-09 Ajinomoto Co., Inc. Cyclopropane derivative

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0502690A2 (en) * 1991-03-05 1992-09-09 Ajinomoto Co., Inc. Cyclopropane derivative

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Regio- and Enantioselective N-Allylations of Imidazole,Benzimidazole, and Purine Heterocycles Catalyzed by Single-Component Metallacyclic Iridium Complexes;Levi M.Stanley, et al.;《J.AM.CHEM.SOC.》;20091231;第131卷(第25期);第8971-8983页 *
Synthesis and Antiherpetic Activity of (±)-9-[[(Z)-2-Hydroxymethyl)cyclopropyl]methyl]guanine and Related Compounds;Wallace T.Ashton, et al.;《J.Med.Chem.》;19881231;第31卷(第12期);第2304-2315页 *
无环嘌呤核苷化合物2-(2-(6-氨基-2-烷硫基-9H-嘌呤-9-基) 乙基) 丙二酸二甲酯的合成;王馨悦等;《北京化工大学学报( 自然科学版)》;20111231;第38卷(第6期);第29-33页 *

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