CN105272953A - 一种合成苯并呋喃萘醌衍生物的方法 - Google Patents

一种合成苯并呋喃萘醌衍生物的方法 Download PDF

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CN105272953A
CN105272953A CN201510717080.7A CN201510717080A CN105272953A CN 105272953 A CN105272953 A CN 105272953A CN 201510717080 A CN201510717080 A CN 201510717080A CN 105272953 A CN105272953 A CN 105272953A
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naphthoquinone
cumarone
acid
raw material
cdcl
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马大友
刘苏友
龙丽君
谢朵朵
刘丽君
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Central South University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/92—Naphthofurans; Hydrogenated naphthofurans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
    • C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
    • C07J73/003—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by oxygen as hetero atom

Abstract

本发明公开了一种合成苯并呋喃萘醌衍生物的方法，是以2-羟基-3-取代乙烯基-1，4-萘醌为原料，在单质碘的作用下，于有机溶剂中环合成角型的苯并呋喃萘醌衍生物；或者以2-羟基-3-取代乙烯基-1，4-萘醌为原料，先在单质碘的作用下，于有机溶剂中环合成角型苯并呋喃萘醌衍生物，然后将角型苯并呋喃萘醌衍生物在酸性条件下合成直型苯并呋喃萘醌衍生物。该方法实验步骤少，操作简单，选择性高且产率高，具有较高的应用价值。

Description

一种合成苯并呋喃萘醌衍生物的方法
技术领域
本发明属于化学领域，具体涉及一种合成苯并呋喃萘醌衍生物的方法。
背景技术
苯并呋喃萘醌衍生物具有广泛的生理活性，如抗肿瘤、神经保护，抗动脉粥样硬化，抗菌、抗炎等。如从紫葳科(Bignoniaceae)植物中提取的直型呋喃萘醌1-4显示了较好的抗肿瘤活性(Phytochemistry1994,36,323-325；J.Nat.Prod.1993,56,1500-1505；Chem.Pharm.Bull.2013,61,670-673；Bioorg.Med.Chem.2009,17,6286-6291.)。尤其是化合物3最近作为一种新型肿瘤干细胞抑制剂进入了Ib期临床研究(Proc.Natl.Acad.Sci.USA.2015,112,1839-1844.)。
角形苯并呋喃萘醌化合物5也显示了较强的抗肿瘤活性，其作用机制可能是抑制EGFRandPI3K/Akt信号通路(Clin.Exp.Pharmacol.Physiol.2014,41,716-726；Eur.J.Pharmacol.2010,636,52-58；LifeSci.2010,86,207-213.).角形苯并呋喃萘醌化合物丹参酮IIA(6)在临床上用于治疗心血管疾病，如冠心病、心绞痛、心肌梗死、室性早搏等(ExpertOpin.Ther.Patents2013,23,19-29.)。
化合物1,3可以较简便的通过角型苯并呋喃萘醌化合物8a氧化制备得到。角型苯并呋喃萘醌化合物8b和直型苯并呋喃萘醌化合物9b也显示了较好的抗肿瘤活性(J.Med.Chem.1987,30,2005-2008)。
现已经报导的苯并呋喃萘醌衍生物的合成方法有很多种，如通过2-羟基-1，4-萘醌、异腈和醛的三组分反应；通过2-羟基-1，4萘醌和3，4-二溴-2-丁酮的缩合反应；硝酸铈介导的2-羟基-1，4萘醌和烯基硫醚或烯醇醚的缩合反应；2-羟基-3-碘-1，4萘醌和末端炔烃的耦合关环反应等(Tetrahedron2007,63,10269-10275；J.Chem.Soc.,PerkinTrans.I2001,2946-2957；Synth.Commun.2003,33,4123-4135；TetrahedronLett.1997,38,837-840；J.Chem.Soc.,PerkinTrans.I1990,441-445；J.Org.Chem.1993,58,4614-4618)。但是这些方法有着很多的缺点，如直型产物和角形产物选择性低、反应步数多操作复杂、产率低下、需要毒性大的重金属等。
因此，研制一种新的合成方法来制备苯并呋喃萘醌衍生物具有重要意义。
发明内容
本发明旨在克服上述现有技术中的不足，提供一种合成苯并呋喃萘醌衍生物的方法。
为了达到上述目的，本发明提供的技术方案为：
所述合成苯并呋喃萘醌衍生物的方法是以2-羟基-3-取代乙烯基-1，4-萘醌(可参考文献方法合成J.Chem.Soc.,PerkinTrans.I1986,659-664)为原料，在单质碘的作用下，于有机溶剂中环合成角型的苯并呋喃萘醌衍生物；或者以2-羟基-3-取代乙烯基-1，4-萘醌为原料，先在单质碘的作用下，于有机溶剂中环合成角型苯并呋喃萘醌衍生物，然后将角型苯并呋喃萘醌衍生物在酸性条件下合成(优选一锅法)直型苯并呋喃萘醌衍生物；所述有机溶剂选自四氢呋喃、乙腈、二氯甲烷、氯仿、二氧六环、乙醇、甲醇、异丙醇、DMSO、甲苯、二甲苯、N，N-二甲基甲酰胺、N，N-二甲基乙酰胺、醋酸中的一种或多种。
所述2-羟基-3-取代乙烯基-1，4-萘醌结构式如式(Ⅰ)所示：
其中，R1，R2分别或独立的为氢、烷基、苯基或取代苯基，或R1,R2成环为(CH2)4，其中取代苯基中苯环上的取代基选自C1--C6的烷基、C1--C6的烷氧基、卤原子
优选地，所述式(Ⅰ)具体为式(7a)至(7j)所示的如下化合物：
其中，所述的酸选自盐酸、硫酸、磷酸、醋酸、氢溴酸、三氟醋酸中的一种或多种。
所述方法中合成反应的温度为0℃-150℃，优选为25-100℃。
所述单质碘与原料的摩尔比为(1～3)：1，所述有机溶剂与原料的质量比为(10～180)：1，所述酸与原料的质量比为(1～300)：1。
下面对本发明作进一步说明：
为实现上述发明目的，本发明的技术方案是：
本发明所述合成苯并呋喃萘醌衍生物的方法，具体如下合成路线：
合成角型苯并呋喃萘醌衍生物的具体路线为：
其中，R1，R2为分别或独立的可以是氢、烷基、苯及取代苯基等。或R1,R2组合为(CH2)4。
在角型苯并呋喃萘醌衍生物的基础上进一步合成直型苯并呋喃萘醌衍生物的具体路线为：
其中，R1,R2为分别或独立的可以是氢、烷基、苯及取代苯基等。或R1,R2组合为(CH2)4。
本发明以2-羟基-3-取代乙烯基-1，4-萘醌为原料，选取廉价易得的试剂和溶剂，通过控制反应温度、时间、试剂和溶剂的类型等条件，高效、选择性制备直型和角形苯并呋喃萘醌衍生物的方法。该方法实验步骤少，操作简单，且产率较高，具有很大的应用价值。
与现有技术相比，本发明的优势在于：
(1)本发明提供了一种新的合成路线；
(2)本发明和选择性制备直型和角形的苯并呋喃萘醌衍生物；
(3)本发明的合成方法实验步骤少，操作简单，且产率较高，具有较高的应用价值。
具体实施方式实施例中所用原料均为按现有文献报道而合成的
实施例1
114mg(0.5mmol)2-羟基-3-丁烯-1-基-1,4-萘醌7a溶于5mL四氢呋喃中，加入单质碘127mg(0.5mmol,).室温搅拌2小时后，TLC显示原料反应完全，加入30mL水,用乙酸乙酯萃取反应液(15mLX3).合并乙酸乙酯萃取液，加入无水硫酸镁干燥，过滤，浓缩后用硅胶柱层析进行纯化，洗脱剂为石油醚：乙酸乙酯(15:1)，得角形苯并呋喃萘醌化合物2-ethylnaphtho[1,2-b]furan-4,5-dione8a:红色固体,产率89％,mp136-138℃,1HNMR(400MHz,CDCl3)δ8.08(d,J＝8.0Hz,1H),7.69(d,J＝7.2Hz,1H),7.65(t,J＝7.2Hz,1H),7.45(td,J＝7.2,1.2Hz,1H),6.48(s),2.78(q,J＝7.6Hz,2H),1.34(t,J＝7.6Hz,3H)；13CNMR(100MHz,CDCl3)δ180.8,174.5,161.5,159.6,135.3,130.4,129.8,128.8,128.7,122.5,122.0,103.0,21.3,11.7；HRMS(ESI)m/z[M+H]+calcd.forC14H11O3,227.0708,found227.0699.
对以上制备8a的反应条件的温度，原料配比，溶剂等条件进行了优化，具体结果如表1所示.
表1
实施例2
参照实施例1的方法，2-methylnaphtho[1,2-b]furan-4,5-dione8b:红色固体,产率93％,mp162-163℃,1HNMR(500MHz,CDCl3)δ8.07(dd,J＝7.5,1.0Hz,1H),7.69-7.63(m,2H),7.44(td,J＝7.6,1.5Hz,1H),6.47(q,J＝1.5Hz,1H),2.45(d,J＝1.5Hz,3H)；13CNMR(100MHz,CDCl3)δ180.8,174.4,159.7,155.9,135.3,130.5,129.8,128.8,128.7,122.7,122.0,104.6,13.6；HRMS(ESI)m/z[M+H]+calcd.forC13H9O3,213.0552,found213.0543.
实施例3
参照实施例1的方法，2-isopropylnaphtho[1,2-b]furan-4,5-dione8c:红色固体,产率64％,mp92-94℃,1HNMR(400MHz,CDCl3)δ8.06(d,J＝7.6Hz,1H),7.69(d,J＝7.2Hz,1H),7.64(t,J＝7.2Hz,1H),7.43(t,J＝7.2Hz,1H),6.46(s,1H),3.09-3.01(m,1H),1.36(s,3H),1.35(s,3H)；13CNMR(125MHz,CDCl3)δ180.8,175.6,165.4,159.5,135.3,130.5,129.8,128.9,128.8,122.4,122.0,101.9,27.9,20.7；HRMS(ESI)m/z[M+H]+calcd.ForC15H13O3,241.0865,found241.0853.
实施例4
参照实施例1的方法，7,8,9,10-tetrahydrobenzo[d]naphtho[1,2-b]furan-5,6-dione8d:红色固体,产率45％,mp159-161℃,1HNMR(500MHz,CDCl3)δ8.05(dd,J＝8.0,1.0Hz,1H),7.67-7.60(m,2H),7.43-7.39(m,1H),2.76-2.68(m,4H),1.95-1.89(m,2H),1.83-1.77(m,2H)；13CNMR(100MHz,CDCl3)δ181.0,175.3,158.9,154.5,135.3,130.3,129.3,129.1,128.5,121.8,121.2,118.1,23.0,22.4,22.2,21.2；HRMS(ESI)m/z[M+H]+calcd.ForC16H13O3,253.0865,found253.0855.
实施例5
参照实施例1的方法，2-phenylnaphtho[1,2-b]furan-4,5-dione[5]8e:红色固体,产率63％,mp219-220℃,1HNMR(400MHz,CDCl3)δ8.13(dd,J＝7.6,0.8Hz,1H),7.85(d,J＝7.6Hz,1H),7.80-7.78(m,2H),7.74-7.70(m,1H),7.52-7.48(m,3H),7.45-7.41(m,1H),7.09(s,1H)；13CNMR(100MHz,CDCl3)δ180.5,174.5,159.8,156.8,135.5,130.7,130.2,129.3,129.0,128.9,128.7,128.5,124.5,123.4,122.3,102.9；HRMS(ESI)m/z[M+H]+calcd.forC18H11O3,275.0708,found:275.0699.
实施例6
参照实施例1的方法，2-(4-methoxyphenyl)naphtho[1,2-b]furan-4,5-dione8f:红色固体,产率91％,mp206-207℃,1HNMR(400MHz,CDCl3)δ8.11(dd,J＝7.7,0.9Hz,1H),7.81(d,J＝7.0Hz,1H),7.74-7.67(m,3H),7.48(td,J＝7.6,1.1Hz,1H),7.05–6.99(m,2H),6.94(s,1H),3.90(s,3H)；13CNMR(100MHz,CDCl3)δ180.6,174.6,160.5,159.4,156.9,135.4,130.6,130.0,128.8,128.7,126.1,123.5,122.1,121.6,114.5,101.2,55.4；HRMS(ESI)m/z[M+H]+calcd.ForC19H12O4,305.0814,found305.0812.
实施例7
参照实施例1的方法，2-(3,4-dimethoxyphenyl)naphtho[1,2-b]furan-4,5-dione8g:红色固体,产率57％,mp194-195℃,1HNMR(500MHz,CDCl3)δ8.11(dd,J＝7.7,0.8Hz,1H),7.82(dd,J＝7.6,0.8Hz,1H),7.70(td,J＝7.6,1.2Hz,1H),7.48(td,J＝7.5,1.0Hz,1H),7.38(dd,J＝8.3,2.0Hz,1H),7.24(d,J＝2.0Hz,1H),6.97(d,J＝5.8Hz,1H),6.96(s,1H),4.01(s,3H),3.97(s,3H)；13CNMR(125MHz,CDCl3)δ180.5,174.5,159.4,156.9,150.2,149.4,135.4,130.7,130.0,128.9,128.6,123.5,122.1,121.8,117.7,111.5,107.7,101.6,56.1；HRMS(ESI)m/z[M+H]+calcd.forC20H15O5,335.0920,found335.0924.
实施例8
参照实施例1的方法，2-(2-methylphenyl)naphtho[1,2-b]furan-4,5-dione8h:红色固体,产率91％,mp240-241℃,1HNMR(400MHz,CDCl3)δ8.12(d,J＝7.6Hz,1H),7.84-7.77(m,2H),7.70(t,J＝7.4Hz,1H),7.50(t,J＝7.5Hz,1H),7.39-7.31(m,3H),6.98(s,1H),2.58(s,3H)；13CNMR(100MHz,CDCl3)δ180.5,174.6,160.0,156.4,135.5,135.4,131.6,130.7,130.3,129.2,129.0,128.5,128.1,127.4,126.3,123.2,122.3,106.4,21.9；HRMS(ESI)m/z[M+H]+calcd.forC19H13O3,289.0865,found289.0865.
实施例9
参照实施例1的方法，2-(4-methylphenyl)naphtho[1,2-b]furan-4,5-dione8i:红色固体,产率90％,mp263-264℃,1HNMR(500MHz,CDCl3)δ8.11(dd,J＝7.7,0.7Hz,1H),7.83(d,J＝7.6Hz,1H),7.72-7.66(m,3H),7.49(td,J＝7.6,1.0Hz,1H),7.29(d,J＝8.0Hz,1H),7.02(s,1H),2.44(s,3H)；13CNMR(126MHz,CDCl3)δ180.5,174.5,159.5,157.1,139.5,135.4,130.6,130.1,129.7,128.9,128.6,126.0,124.5,123.4,122.2,102.2,21.4；HRMS(ESI)m/z[M+H]+calcd.ForC19H13O3,289.0865,found289.0867.
实施例10
参照实施例1的方法，2-(2-bromophenyl)naphtho[1,2-b]furan-4,5-dione8j:红色固体,产率86％,mp230-231℃,1HNMR(500MHz,CDCl3)δ8.14(d,J＝7.4Hz,1H),7.88(dd,J＝7.9,1.5Hz,1H),7.84(d,J＝7.5Hz,1H),7.75(d,J＝7.5Hz,1H),7.71(td,J＝7.6,0.9Hz,1H),7.56(s,1H),7.52(t,J＝7.3Hz,1H),7.48(t,J＝7.3Hz,1H),7.31–7.26(m,1H)；13CNMR(125MHz,CDCl3)δ180.4,174.5,160.0,154.3,135.5,134.5,130.7,130.5,130.2,129.4,129.2,129.1,128.3,127.6,122.9,122.4,120.6,108.4；HRMS(ESI)m/z[M+H]+calcd.forC18H10BrO3,352.9813,found:352.9819.
实施例11
114mg(0.5mmol)2-羟基-3-丁烯-1-基-1,4-萘醌7a溶于5mL四氢呋喃中，加入单质碘127mg(0.5mmol,).室温搅拌2小时后，TLC显示原料反应完全，加入5mL浓HCl,50℃下搅拌1小时,加入30mL水,用乙酸乙酯萃取反应液(15mLX3).合并乙酸乙酯萃取液，加入无水硫酸镁干燥，过滤，浓缩后用硅胶柱层析进行纯化，洗脱剂为石油醚：乙酸乙酯(15:1)，得直形苯并呋喃萘醌化合物2-ethylnaphtho[2,3-b]furan-4,9-dione9a:黄色固体,产率73％,mp145-146℃,1HNMR(400MHz,CDCl3)δ8.25-8.22(m,1H),8.20-8.18(m,1H),7.79-7.73(m,2H),6.65(s),2.87(q,J＝7.6Hz,2H),1.39(t,J＝7.6Hz,3H)；13CNMR(100MHz,CDCl3)δ180.9,173.1,165.8,151.6,133.8,133.5,133.1,132.6,131.8,126.84,126.77,103.5,21.8,11.6；HRMS(ESI)m/z[M+H]+calcd.ForC14H11O3,227.0708,found:227.0699.
实施例12
参照实施例11的方法，2-methylnaphtho[2,3-b]furan-4,9-dione9b:黄色固体,产率75％,mp243-245℃,1HNMR(400MHz,CDCl3)δ8.24-8.22(m,1H),8.20-8.18(m,1H),7.79-7.73(m,2H),6.64(q,J＝0.8Hz,1H),2.54(d,J＝0.4Hz,3H)；13CNMR(100MHz,CDCl3)δ180.8,174.4,159.7,155.9,135.3,130.5,129.8,128.8,128.7,122.7,122.0,104.6,13.6；HRMS(ESI)m/z[M+H]+calcd.ForC13H9O3,213.0552,found:213.0542.
实施例13
参照实施例11的方法，2-isopropylnaphtho[2,3-b]furan-4,9-dione9c:黄色固体,产率56％,mp101-103℃,1HNMR(400MHz,CDCl3)δ8.24-8.22(m,1H),8.19-8.17(m,1H),7.78-7.72(m,2H),6.63(s,1H),3.19-3.11(m,1H),1.40(s,3H),1.39(s,3H)；13CNMR(100MHz,CDCl3)δ181.0,173.2,169.8,151.1,133.8,133.5,133.1,132.7,131.7,126.9,126.8,102.3,28.4,20.7；HRMS(ESI)m/z[M+H]+calcd.forC15H13O3,241.0865,found:241.0854.
实施例14
参照实施例11的方法，1,2,3,4-tetrahydrobenzo[d]naphtho[2,3-b]furan-6,11-dione9d:黄色固体,产率26％,mp209-210℃,1HNMR(500MHz,CDCl3)δ8.23-8.21(m,1H),8.17-8.15(m,1H),7.78-7.71(m,2H),2.87-2.83(m,2H),2.82-2.78(m,2H),1.99-1.93(m,2H),1.88-1.83(m,2H)；13CNMR(125MHz,CDCl3)δ182.1,173.2,159.8,151.1,133.6,133.4,133.3,132.8,129.4,126.7,126.6,118.7,23.5,22.2,22.1,21.3；HRMS(ESI)m/z[M+H]+calcd.ForC16H13O3,253.0865,found:253.0854.
实施例15
参照实施例11的方法，2-phenylnaphtho[2,3-b]furan-4,9-dione9e:黄色固体,产率47％,mp249-251℃,1HNMR(400MHz,CDCl3)δ8.29-8.28(m,1H),8.24-8.22(m,1H),7.94-7.91(m,2H),7.82-7.76(m,2H),7.55-7.46(m,3H),7.23(s,1H)；13CNMR(125MHz,CDCl3)δ180.8,173.0,160.4,151.6,134.0,133.6,133.1,132.9,132.4,130.3,129.1,128.4,127.0,126.9,125.6,102.9；HRMS(ESI)m/z[M+H]+calcd.ForC18H11O3,275.0708,found:275.0699.
实施例16
参照实施例11的方法，2-(4-methoxyphenyl)naphtho[2,3-b]furan-4,9-dione9f:黄色固体,产率86％,mp215-216℃,1HNMR(400MHz,CDCl3)δ8.23(m,2H),7.88-7.83(m,2H),7.81-7.71(m,2H),7.08(s,1H),7.05-6.98(m,2H),3.90(s,3H)；13CNMR(100MHz,CDCl3)δ181.0,172.8,161.3,160.6,151.1,133.9,133.5,133.1,132.9,132.7,127.3,126.9,126.8,121.1,114.6,101.4,55.5；HRMS(ESI)m/z[M+H]+calcd.ForC19H12O4,305.0814,found:305.0818.
实施例17
参照实施例11的方法，2-(3,4-dimethoxyphenyl)naphtho[2,3-b]furan-4,9-dione9g:黄色固体,产率50％,mp217-218℃,1HNMR(500MHz,CDCl3)δ8.27(dd,J＝7.4,1.5Hz,1H),8.22(dd,J＝7.4,1.6Hz,1H),7.82-7.74(m,2H),7.51(dd,J＝8.4,2.0Hz,1H),7.41(d,J＝2.0Hz,1H),7.12(s,1H),6.99(d,J＝8.4Hz,1H),4.02(s,3H),3.98(s,3H)；13CNMR(125MHz,CDCl3)δ181.0,172.8,160.6,151.1,151.0,149.5,134.0,133.5,133.1,133.0,132.8,126.9,126.8,121.3,119.2,111.5,108.3,101.8,56.2,56.1；HRMS(ESI)m/z[M+H]+calcd.ForC20H15O5,335.0920,found:335.0924.
实施例18
参照实施例11的方法，2-(2-methylphenyl)naphtho[2,3-b]furan-4,9-dione9h:黄色固体,产率75％,mp240-241℃,1HNMR(500MHz,CDCl3)δ8.28-8.20(m,2H),7.93-7.90(m,1H),7.82-7.74(m,2H),7.41-7.32(m,3H),7.12(s,1H),2.62(s,3H)；13CNMR(125MHz,CDCl3)δ181.0,173.1,160.1,151.3,136.3,134.0,133.6,133.2,132.9,132.1,131.6,130.0,128.4,127.8,126.9,126.8,126.4,106.3,21.92；HRMS(ESI)m/z[M+H]+calcd.ForC19H13O3,289.0865,found:289.0868.
实施例19
参照实施例11的方法，2-(4-methylphenyl)naphtho[2,3-b]furan-4,9-dione9i:黄色固体,产率78％,mp266-267℃,1HNMR(500MHz,CDCl3)δ8.26(dd,J＝7.3,1.5Hz,1H),8.21(dd,J＝7.3,1.5Hz,1H),7.82-7.73(m,4H),7.30(d,J＝8.0Hz,2H),7.15(s,1H),2.43(s,3H)；13CNMR(125MHz,CDCl3)δ181.0,173.0,160.7,151.3,140.7,133.9,133.5,133.1,132.9,132.5,129.8,126.9,126.8,125.6,125.5,102.3,21.5；HRMS(ESI)m/z[M+H]+calcd.forC19H13O3,289.0865,found:289.0868.
实施例20
114mg(0.5mmol)2-羟基-3-丁烯-1-基-1,4-萘醌7a溶于5mL四氢呋喃中，加入单质碘127mg(0.5mmol,).室温搅拌2小时后，TLC显示原料反应完全，加入5mL50％硫酸,50℃下搅拌1小时,加入30mL水,用乙酸乙酯萃取反应液(15mLX3).合并乙酸乙酯萃取液，加入无水硫酸镁干燥，过滤，浓缩后用硅胶柱层析进行纯化，洗脱剂为石油醚：乙酸乙酯(15:1)，得直形苯并呋喃萘醌化合物9a:黄色固体,产率70％。
实施例21
114mg(0.5mmol)2-羟基-3-丁烯-1-基-1,4-萘醌7a溶于5mL醋酸中，加入单质碘127mg(0.5mmol,).室温搅拌2小时后，TLC显示原料反应完全，加入5mL三氟醋酸,80℃下搅拌3小时,加入30mL水,用乙酸乙酯萃取反应液(15mLX3)。合并乙酸乙酯萃取液，加入无水硫酸镁干燥，过滤，浓缩后用硅胶柱层析进行纯化，洗脱剂为石油醚：乙酸乙酯(15:1)，得直形苯并呋喃萘醌化合物9a:黄色固体,产率68％。

Claims (8)

1.一种合成苯并呋喃萘醌衍生物的方法，其特征在于，所述方法是以2-羟基-3-取代乙烯基-1，4-萘醌为原料，在单质碘的作用下，于有机溶剂中环合成角型苯并呋喃萘醌衍生物；所述有机溶剂选自四氢呋喃、乙腈、二氯甲烷、氯仿、二氧六环、乙醇、甲醇、异丙醇、DMSO、甲苯、二甲苯、N，N-二甲基甲酰胺、N，N-二甲基乙酰胺、醋酸中的一种或多种；所述2-羟基-3-取代乙烯基-1，4-萘醌结构式如式(Ⅰ)所示：
其中，R1，R2分别或独立的为氢、C1--C6烷基、苯基或取代苯基，或R1,R2成环为(CH2)4，其中取代苯基中苯环上的取代基选自C1--C6的烷基、C1--C6的烷氧基、卤原子。
2.如权利要求1所述的方法，其特征在于，所述式(Ⅰ)具体为式(7a)至(7j)所示的如下化合物：
3.如权利要求1或2所述的方法，其特征在于，所述方法是以2-羟基-3-取代乙烯基-1，4-萘醌为原料，先在单质碘的作用下，于有机溶剂中环合成角型苯并呋喃萘醌衍生物，然后将角型苯并呋喃萘醌衍生物在酸性条件下合成直型苯并呋喃萘醌衍生物。
4.如权利要求3所述的方法，其特征在于，所述的酸选自盐酸、硫酸、磷酸、醋酸、氢溴酸、三氟醋酸中的一种或多种。
5.如权利要求3所述的方法，其特征在于，所述方法中合成反应的温度为0℃-150℃。
6.如权利要求5所述的方法，其特征在于，所述方法中合成反应的温度为25-100℃。
7.如权利要求3所述的方法，其特征在于，所述单质碘与原料的摩尔比为(1～3)：1，所述有机溶剂与原料的质量比为(10～180)：1。
8.如权利要求3所述的方法，其特征在于，所述酸与原料的质量比为(1～300)：1。
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Publication number Priority date Publication date Assignee Title
CN106380456A (zh) * 2016-08-29 2017-02-08 中南大学 一种合成苯并呋喃萘醌衍生物的方法
CN107973788A (zh) * 2018-01-09 2018-05-01 沈阳药科大学 Bbi608衍生物及其制备与用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
S. LIU ET AL.: "The iodine-mediated highly regioselective synthesis of angular and linear naphthofuroquinones", 《TETRAHEDRON LETTERS》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106380456A (zh) * 2016-08-29 2017-02-08 中南大学 一种合成苯并呋喃萘醌衍生物的方法
CN106380456B (zh) * 2016-08-29 2019-03-26 中南大学 一种合成苯并呋喃萘醌衍生物的方法
CN107973788A (zh) * 2018-01-09 2018-05-01 沈阳药科大学 Bbi608衍生物及其制备与用途
CN107973788B (zh) * 2018-01-09 2021-07-09 沈阳药科大学 Bbi608衍生物及其制备与用途

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