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化学进展 2019, Vol. 31 Issue (10): 1362-1371 DOI: 10.7536/PC190519 前一篇   后一篇

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Ugi/Diels-Alder串联反应在构建杂环化合物中的应用

商天奕1, 吕琪妍2, 刘琰1,**(), 於兵2,**()   

  1. 1. 信阳农林学院生物与制药工程学院 信阳 464000
    2. 郑州大学化学与分子工程学院 郑州 450001
  • 收稿日期:2019-05-18 出版日期:2019-10-15 发布日期:2019-08-05
  • 通讯作者: 刘琰, 於兵
  • 基金资助:
    国家自然科学基金项目(21501010); 中国博士后科学基金项目(2019M652561); 河南省高等学校重点科研项目(20B150021); 信阳农林学院青年教师科研基金项目(201701009)
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Application of Ugi/Diels-Alder Tandem Reaction in the Construction of Heterocyclic Compounds

Tianyi Shang1, Qiyan Lv2, Yan Liu1,**(), Bing Yu2,**()   

  1. 1. College of Biological and Pharmaceutical Engineering, Xinyang Agriculture and Forestry University, Xinyang 464000, China
    2. College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, China
  • Received:2019-05-18 Online:2019-10-15 Published:2019-08-05
  • Contact: Yan Liu, Bing Yu
  • About author:
    ** E-mail: (Yan Liu);
    (Bing Yu)
  • Supported by:
    National Natural Science Foundation of China(21501010); China Postdoctoral Science Foundation(2019M652561); Key Research Project of Higher Education Institutions in Henan Province(20B150021); Research Fund of Xinyang Agriculture and Forestry University for Young Teachers(201701009)

杂环化合物广泛存在于天然产物和药物分子中,许多杂环化合物还具有潜在生物活性和药理作用。因此,如何快速高效地构建小分子杂环化合物库成为当今有机合成和药物化学领域的研究热点。Ugi反应在多样性导向合成方面具有得天独厚的优势,能够解决待合成化合物数量庞大、结构复杂的难题;同时,Diels-Alder [4+2]环加成反应能够高效构建碳-碳键,以较高的立体选择性和区域选择性合成六元环系。目前,集二者于一身的Ugi/Diels-Alder串联反应在构建杂环化合物方面展现出了巨大优势和无穷潜能。本文以不同类型的DA反应分类:按照呋喃作为双烯体、吡咯作为双烯体、噻吩为双烯体、口恶唑作为双烯体、 1,2,4-三嗪作为双烯体、苯作为双烯体、不饱和键和芳环共同作为双烯体等对UDA串联反应的研究进行了综述。

关键词： 杂环化合物, Ugi反应, Diels-Alder反应, 串联反应

Heterocyclic compounds are widely present in natural products and drug molecules and many of them also have potential biological activities and pharmacological effects. Therefore, methodologies toward rapid and efficient construction of heterocyclic compound libraries have become one of the research hotspots in the fields of organic synthesis and pharmaceutical chemistry. Ugi reaction has unique advantages in diversity-oriented synthesis to generate a large number of target products with structural complexity. Meanwhile, Diels-Alder [4+2] cycloaddition reaction can efficiently form carbon-carbon bonds to access various heterocyclic rings with good stereo- and region-selectivity. Nowadays, Ugi/Diels-Alder tandem reaction, which combine merits of the two, presents enormous advantages and infinite potential in synthesis of heterocyclic compounds. In this paper, the recent advances in Ugi/Diels-Alder tandem reaction is summarized and reviewed according to the types of dienes in DA reactions, such as furan, pyrrole, thiophene, oxazole, 1,2,4-triazine, benzene, and unsaturated bond with aromatic ring.

Key words: heterocyclic compounds, Ugi reaction, Diels-Alder reaction, tandem reaction
()
图式1 经典Ugi四组分反应
Scheme. 1 Classical Ugi four-component reaction
图1 Ugi分子内双官能团参与的杂环化合物构建
Fig. 1 Construction of heterocyclic compounds via intramolecular bifunctional groups in Ugi adducts
图式2 通过UDA串联反应合成化合物2和3[35, 36]
Scheme. 2 Synthesis of 2 and 3 via UDA tandem reaction[35, 36]
图式3 UDA消除芳构化历程[37]
Scheme. 3 A UDA/deselenization/aromatization sequence[37]
图式4 通过US/IMDA串联反应合成化合物6[39]
Scheme. 4 Synthesis of 6 via US/IMDA tandem reaction[39]
图式5 通过UDA串联反应固相合成化合物8[35]
Scheme. 5 Solid phase synthesis of 8 via UDA tandem reaction[35]
图式6 Solid phase synthesis of 11 via UDA tandem reaction[40]
Scheme. 6 通过UDA串联反应固相合成化合物11[40]
图式7 通过UDA串联反应固相合成化合物14[41]
Scheme. 7 Solid phase synthesis of 14 via UDA tandem reaction[41]
图式8 通过UDA串联反应合成化合物19[42]
Scheme. 8 Synthesis of 19 via UDA tandem reaction[42]
图式9 通过UDA串联反应合成化合物22[44]
Scheme. 9 Synthesis of 22 via UDA tandem reaction[44]
图式10 炔基与吡咯参与的UDA串联反应通式[44, 45]
Scheme. 10 UDA tandem reaction formula via addition of the alkyne and pyrrole[44, 45]
图式11 通过UDA串联反应合成化合物24[46]
Scheme. 11 Synthesis of 24 via UDA tandem reaction[46]
图式12 通过三组分反应构建多取代口恶唑[49,50,51,52]
Scheme. 12 Synthesis of polysubstituted oxazole via three component reaction[49,50,51,52]
图式13 通过UDA串联反应合成化合物27[55]
Scheme. 13 Synthesis of 27 via UDA tandem reaction[55]
图式14 通过UDA串联反应合成化合物29[53]
Scheme. 14 Synthesis of 29 via UDA tandem reaction[53]
图式15 通过UDA串联反应合成HMBA[56]
Scheme. 15 Synthesis of HMBA via UDA tandem reaction[56]
图式16 通过UDA串联反应合成化合物30[54]
Scheme. 16 Synthesis of 30 via UDA tandem reaction[54]
图式17 通过UDA串联反应合成化合物34[57]
Scheme. 17 Synthesis of 34 via UDA tandem reaction[57]
图式18 通过UDA串联反应合成化合物35[58]
Scheme. 18 Synthesis of 35 via UDA tandem reaction[58]
图式19 通过UDA串联反应合成化合物36[59]
Scheme. 19 Synthesis of 36 via UDA tandem reaction[59]
图式20 通过UDA串联反应合成化合物39[60]
Scheme. 20 Synthesis of 39 via UDA tandem reaction[60]
图式21 通过UDA串联反应合成化合物40[61]
Scheme. 21 Synthesis of 40 via UDA tandem reaction[61]
图式22 Ugi/Diels-Alder/HCl消除的多米诺反应[62]
Scheme. 22 Ugi/Diels-Alder/HCl elimination donimo reaction[62]
图式23 通过Ugi/retro Diels-Alder串联反应合成化合物42[63]
Scheme. 23 Synthesis of 42 via Ugi/retro Diels-Alder tandem reaction[63]
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