注册 English

Direct construction of 3',4'-dihydrospiro[pyrrol-3,2'-oxindoles] through a cascade Michael/cyclization reaction of 3-aminoindolin-2-ones with enones/enals

Dao-Cai Wang ,  Hang Song ,  Chun-Yun Xu ,  Hui Dong ,  Jie Liu

downloadPDF
Citation:  Dao-Cai Wang, Hang Song, Chun-Yun Xu, Hui Dong, Jie Liu. Direct construction of 3',4'-dihydrospiro[pyrrol-3,2'-oxindoles] through a cascade Michael/cyclization reaction of 3-aminoindolin-2-ones with enones/enals[J]. Chinese Chemical Letters, 2015, 26(8): 1050-1053. doi: 10.1016/j.cclet.2015.04.014 shu

Direct construction of 3',4'-dihydrospiro[pyrrol-3,2'-oxindoles] through a cascade Michael/cyclization reaction of 3-aminoindolin-2-ones with enones/enals

    • 通讯作者: Jie Liu,
  • 基金项目:

    Financial support for this work by the National Natural Science Foundation of China (No. 81202403)  (No. 81202403)

    Technology Department Translational Medicine Innovation Foundation (No. ZH13039) are gratefully acknowledged. We also thank Sichuan University Analytical & Testing Center for the NMR analysis. (No. ZH13039)

摘要: A simple and efficient cascade Michael/cyclization reaction of 3-aminoindolin-2-ones with enones/enals was identified for the synthesis of potentially biologically active 3',4'-dihydrospiro[pyrrol-3,2'-oxindoles], using DBU as an efficient catalyst and ethylene glycol as an environmentally benign solvent. More diverse 3',4'-dihydrospiro[pyrrol-3,2'-oxindoles] analog libraries were prepared in good yields (up to 97%). The structure of 3',4'-dihydrospiro[pyrrol-3,2'-oxindoles] was confirmed by mass spectrometry analysis, NMR analysis and single crystal X-ray diffraction. The main advantages of this method include the availability of startingmaterials, simple experimental operation, short reaction time, as well as high yields observed.

English

  • 

    1. [1] R. Rojas-Duran, G. Gonzalez-Aspajo, C. Ruiz-Martel, et al., Anti-inflammatory activity of mitraphylline isolated from Uncaria tomentosa bark, J. Ethnopharmacol. 143 (2012) 801-804.[1] R. Rojas-Duran, G. Gonzalez-Aspajo, C. Ruiz-Martel, et al., Anti-inflammatory activity of mitraphylline isolated from Uncaria tomentosa bark, J. Ethnopharmacol. 143 (2012) 801-804.

    2. [2] I. Gulcin, S. Beydemir, F. Topal, et al., Apoptotic, antioxidant and antiradical effects of majdine and isomajdine from Vinca herbacea Waldst. and kit, J. Enzyme Inhib. Med. Chem. 27 (2012) 587-594.[2] I. Gulcin, S. Beydemir, F. Topal, et al., Apoptotic, antioxidant and antiradical effects of majdine and isomajdine from Vinca herbacea Waldst. and kit, J. Enzyme Inhib. Med. Chem. 27 (2012) 587-594.

    3. [3] J.H. Lu, J.Q. Tan, S.S.K. Durairajan, et al., Isorhynchophylline, a natural alkaloid, promotes the degradation of α-synuclein in neuronal cells via inducing autophagy, Autophagy 8 (2012) 98-108.[3] J.H. Lu, J.Q. Tan, S.S.K. Durairajan, et al., Isorhynchophylline, a natural alkaloid, promotes the degradation of α-synuclein in neuronal cells via inducing autophagy, Autophagy 8 (2012) 98-108.

    4. [4] G.G. Cheng, Y.L. Zhao, Y. Zhang, et al., Indole alkaloids from cultivated Vinca major, Tetrahedron 70 (2014) 8723-8729.[4] G.G. Cheng, Y.L. Zhao, Y. Zhang, et al., Indole alkaloids from cultivated Vinca major, Tetrahedron 70 (2014) 8723-8729.

    5. [5] H.J. Cong, Q. Zhao, S.W. Zhang, et al., Terpenoid indole alkaloids from Mappianthus iodoides Hand. -Mazz., Phytochemistry 100 (2014) 76-85.[5] H.J. Cong, Q. Zhao, S.W. Zhang, et al., Terpenoid indole alkaloids from Mappianthus iodoides Hand. -Mazz., Phytochemistry 100 (2014) 76-85.

    6. [6] Y. Arun, K. Saranraj, C. Balachandran, et al., Novel spirooxindole-pyrrolidine compounds: synthesis, anticancer and molecular docking studies, Eur. J. Med. Chem. 74 (2014) 50-64.[6] Y. Arun, K. Saranraj, C. Balachandran, et al., Novel spirooxindole-pyrrolidine compounds: synthesis, anticancer and molecular docking studies, Eur. J. Med. Chem. 74 (2014) 50-64.

    7. [7] J.M. Yang, Y. Hu, Q. Li, et al., Efficient and regioselective synthesis of novel functionalized dispiropyrrolidines and their cytotoxic activities, ACS Comb. Sci. 16 (2014) 139-145.[7] J.M. Yang, Y. Hu, Q. Li, et al., Efficient and regioselective synthesis of novel functionalized dispiropyrrolidines and their cytotoxic activities, ACS Comb. Sci. 16 (2014) 139-145.

    8. [8] B. Yu, X.J. Shi, P.P. Qi, et al., Design, synthesis and biological evaluation of novel steroidal spiro-oxindoles as potent antiproliferative agents, J. Steroid Biochem. Mol. Biol. 141 (2014) 121-134.[8] B. Yu, X.J. Shi, P.P. Qi, et al., Design, synthesis and biological evaluation of novel steroidal spiro-oxindoles as potent antiproliferative agents, J. Steroid Biochem. Mol. Biol. 141 (2014) 121-134.

    9. [9] Y. Kia, H. Osman, R.S. Kumar, et al., Synthesis and discovery of highly functionalized mono-and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors, Bioorg. Med. Chem. Lett. 24 (2014) 1815-1819.[9] Y. Kia, H. Osman, R.S. Kumar, et al., Synthesis and discovery of highly functionalized mono-and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors, Bioorg. Med. Chem. Lett. 24 (2014) 1815-1819.

    10. [10] A. Kaur, B. Singh, B. Vyas, et al., Synthesis and biological activity of 4-aryl-3-benzoyl-5-phenylspiro［pyrrolidine-2.3'-indolin］-2'-one derivatives as novel potent inhibitors of advanced glycation end product, Eur. J. Med. Chem. 79 (2014) 282-289.[10] A. Kaur, B. Singh, B. Vyas, et al., Synthesis and biological activity of 4-aryl-3-benzoyl-5-phenylspiro［pyrrolidine-2.3'-indolin］-2'-one derivatives as novel potent inhibitors of advanced glycation end product, Eur. J. Med. Chem. 79 (2014) 282-289.

    11. [11] A.V. Velikorodov, V.A. Ionova, O.V. Degtyarev, et al., Synthesis and antimicrobial and antifungal activity of carbamate-functionized spiro compounds, Pharm. Chem. J. 46 (2013) 715-719.[11] A.V. Velikorodov, V.A. Ionova, O.V. Degtyarev, et al., Synthesis and antimicrobial and antifungal activity of carbamate-functionized spiro compounds, Pharm. Chem. J. 46 (2013) 715-719.

    12. [12] Y. Arun, G. Bhaskar, C. Balachandran, et al., Facile one-pot synthesis of novel dispirooxindole-pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line, Bioorg. Med. Chem. Lett. 23 (2013) 1839-1845.[12] Y. Arun, G. Bhaskar, C. Balachandran, et al., Facile one-pot synthesis of novel dispirooxindole-pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line, Bioorg. Med. Chem. Lett. 23 (2013) 1839-1845.

    13. [13] R. Murugan, S. Anbazhagan, S.S. Narayanan, Synthesis and in vivo antidiabetic activity of novel dispiropyrrolidines through ［3 + 2］ cycloaddition reactions with thiazolidinedione and rhodanine derivatives, Eur. J. Med. Chem. 44 (2009) 3272-3279.[13] R. Murugan, S. Anbazhagan, S.S. Narayanan, Synthesis and in vivo antidiabetic activity of novel dispiropyrrolidines through ［3 + 2］ cycloaddition reactions with thiazolidinedione and rhodanine derivatives, Eur. J. Med. Chem. 44 (2009) 3272-3279.

    14. [14] R. Rajesh, R. Raghunathan, Synthesis of β-lactam-tethered polycyclic fused heterocycles through a rearrangement by a one-pot tandem ［3 + 2］ cycloaddition reaction, Eur. J. Org. Chem. 13 (2013) 2597-2607.[14] R. Rajesh, R. Raghunathan, Synthesis of β-lactam-tethered polycyclic fused heterocycles through a rearrangement by a one-pot tandem ［3 + 2］ cycloaddition reaction, Eur. J. Org. Chem. 13 (2013) 2597-2607.

    15. [15] K. Suman, L. Srinu, S. Thennarasu, Lewis acid catalyzed unprecedented ［3 + 2］ cycloaddition yields 3,3'-pyrrolidinyldispirooxindoles containing four contiguous chiral stereocenters with two contiguous quaternary spirostereocenters, Org. Lett. 16 (2014) 3732-3735.[15] K. Suman, L. Srinu, S. Thennarasu, Lewis acid catalyzed unprecedented ［3 + 2］ cycloaddition yields 3,3'-pyrrolidinyldispirooxindoles containing four contiguous chiral stereocenters with two contiguous quaternary spirostereocenters, Org. Lett. 16 (2014) 3732-3735.

    16. [16] A. Hemamalini, S. Nagarajan, T.M. Das, A novel class of sugar-based ether-linkeddispirooxindolo-pyrrolidines/pyrrolizidines through ［3 + 2］-cycloaddition of azomethine ylides, Carbohydr. Res. 352 (2012) 12-17.[16] A. Hemamalini, S. Nagarajan, T.M. Das, A novel class of sugar-based ether-linkeddispirooxindolo-pyrrolidines/pyrrolizidines through ［3 + 2］-cycloaddition of azomethine ylides, Carbohydr. Res. 352 (2012) 12-17.

    17. [17] S. Purushothaman, R. Prasanna, S. Lavanya, et al., Regio-and stereoselective synthesis of spiro-pyrrolidine/pyrrolizidine/thiazolidine-grafted macrocycles through intramolecular 1,3-dipolar cycloaddition reaction, Tetrahedron Lett. 54 (2013) 5744-5747.[17] S. Purushothaman, R. Prasanna, S. Lavanya, et al., Regio-and stereoselective synthesis of spiro-pyrrolidine/pyrrolizidine/thiazolidine-grafted macrocycles through intramolecular 1,3-dipolar cycloaddition reaction, Tetrahedron Lett. 54 (2013) 5744-5747.

    18. [18] H.B. Yang, Y. Wei, M. Shi, Construction of spiro［indoline］oxindoles through onepot thermal-induced ［3 + 2］ cycloaddition/silica gel-promoted fragmentation sequence between isatin ketonitrones and electron-deficient alkynes, Tetrahedron 69 (2013) 4088-4097.[18] H.B. Yang, Y. Wei, M. Shi, Construction of spiro［indoline］oxindoles through onepot thermal-induced ［3 + 2］ cycloaddition/silica gel-promoted fragmentation sequence between isatin ketonitrones and electron-deficient alkynes, Tetrahedron 69 (2013) 4088-4097.

    19. [19] Y.M. Cao, F.F. Shen, F.T. Zhang, et al., Catalytic asymmetric Michael addition/ cyclization of isothiocyanato oxindoles: highly efficient and versatile approach for the synthesis of 3,2'-pyrrolidinyl mono-and bi-spirooxindole frameworks, Chem. Eur. J. 19 (2013) 1184-1188.[19] Y.M. Cao, F.F. Shen, F.T. Zhang, et al., Catalytic asymmetric Michael addition/ cyclization of isothiocyanato oxindoles: highly efficient and versatile approach for the synthesis of 3,2'-pyrrolidinyl mono-and bi-spirooxindole frameworks, Chem. Eur. J. 19 (2013) 1184-1188.

    20. [20] F. Tan, L.Q. Lu, Q.Q. Yang, et al., Enantioselective cascade Michael addition/ cyclization reactions of 3-nitro-2H-chromenes with 3-isothiocyanato oxindoles: efficient synthesis of functionalized polycyclic spirooxindoles, Chem. Eur. J. 20 (2014) 3415-3420.[20] F. Tan, L.Q. Lu, Q.Q. Yang, et al., Enantioselective cascade Michael addition/ cyclization reactions of 3-nitro-2H-chromenes with 3-isothiocyanato oxindoles: efficient synthesis of functionalized polycyclic spirooxindoles, Chem. Eur. J. 20 (2014) 3415-3420.

    21. [21] Y. Sun, J. Sun, C.G. Yan, Synthesis of 1'-aryl-2'-(2-oxoindolin-3-yl)spiro［indoline-3,5'-pyrroline］-2,3'-dione via one-pot reaction of arylamines, acetone, and isatins, Tetrahedron Lett. 53 (2012) 3647-3649.[21] Y. Sun, J. Sun, C.G. Yan, Synthesis of 1'-aryl-2'-(2-oxoindolin-3-yl)spiro［indoline-3,5'-pyrroline］-2,3'-dione via one-pot reaction of arylamines, acetone, and isatins, Tetrahedron Lett. 53 (2012) 3647-3649.

    22. [22] D. Chen, M.H. Xu, Zn-mediated asymmetric allylation of N-tert-butanesulfinyl ketimines: an efficient and practical access to chiral quaternary 3-aminooxindoles, Chem. Commun. 49 (2013) 1327-1329.[22] D. Chen, M.H. Xu, Zn-mediated asymmetric allylation of N-tert-butanesulfinyl ketimines: an efficient and practical access to chiral quaternary 3-aminooxindoles, Chem. Commun. 49 (2013) 1327-1329.

    23. [23] B. Zhang, P. Feng, L.H. Sun, et al., N-Heterocyclic carbene-catalyzed homoenolate additions with N-aryl ketimines as electrophiles: efficient synthesis of spirocyclic γ-lactam oxindoles, Chem. Eur. J. 18 (2012) 9198-9203.[23] B. Zhang, P. Feng, L.H. Sun, et al., N-Heterocyclic carbene-catalyzed homoenolate additions with N-aryl ketimines as electrophiles: efficient synthesis of spirocyclic γ-lactam oxindoles, Chem. Eur. J. 18 (2012) 9198-9203.

    24. [24] H. Lv, B. Tiwari, J.M. Mo, et al., Highly enantioselective addition of enals to isatinderived ketimines catalyzed by N-heterocyclic carbenes: synthesis of spirocyclic γ-lactams, Org. Lett. 14 (2012) 5412-5415.[24] H. Lv, B. Tiwari, J.M. Mo, et al., Highly enantioselective addition of enals to isatinderived ketimines catalyzed by N-heterocyclic carbenes: synthesis of spirocyclic γ-lactams, Org. Lett. 14 (2012) 5412-5415.

    25. [25] N. Sharma, Z.H. Li, U.K. Sharma, et al., Facile access to functionalized spiro［indoline-3,2'-pyrrole］-2,5'-diones via post-Ugi domino Buchwald-Hartwig/Michael reaction, Org. Lett. 16 (2014) 3884-3887.[25] N. Sharma, Z.H. Li, U.K. Sharma, et al., Facile access to functionalized spiro［indoline-3,2'-pyrrole］-2,5'-diones via post-Ugi domino Buchwald-Hartwig/Michael reaction, Org. Lett. 16 (2014) 3884-3887.

    26. [26] A. Srivastava, S.M. Mobin, S. Samanta, (+/-)-CSA catalyzed one-pot synthesis of 6,7-dihydrospiro［indole-3,1'-isoindoline］-2,3',4(1H,5H)-trione derivatives: easy access of spirooxindoles and ibophyllidine-like alkaloids, Tetrahedron Lett. 55 (2014) 1863-1867.[26] A. Srivastava, S.M. Mobin, S. Samanta, (+/-)-CSA catalyzed one-pot synthesis of 6,7-dihydrospiro［indole-3,1'-isoindoline］-2,3',4(1H,5H)-trione derivatives: easy access of spirooxindoles and ibophyllidine-like alkaloids, Tetrahedron Lett. 55 (2014) 1863-1867.

    27. [27] M.S. Poslusney, B.J. Melancon, P.R. Gentry, et al., Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule, Bioorg. Med. Chem. Lett. 23 (2013) 1860-1864.[27] M.S. Poslusney, B.J. Melancon, P.R. Gentry, et al., Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule, Bioorg. Med. Chem. Lett. 23 (2013) 1860-1864.

    28. [28] H.A. Soliman, T.A. Salama, Silicon-mediated highly efficient synthesis of 1,8-dioxo-octahydroxanthenes and their transformation to novel functionalized pyrano-tetrazolo ［1,5-a］ azepine derivatives, Chin. Chem. Lett. 24 (2013) 404-406.[28] H.A. Soliman, T.A. Salama, Silicon-mediated highly efficient synthesis of 1,8-dioxo-octahydroxanthenes and their transformation to novel functionalized pyrano-tetrazolo ［1,5-a］ azepine derivatives, Chin. Chem. Lett. 24 (2013) 404-406.

    29. [29] V.M. Joshi, R.L. Magar, P.B. Throat, et al., Novel one-pot synthesis of 4H-chromene derivatives using amino functionalized silica gel catalyst, Chin. Chem. Lett. 25 (2014) 455-458.[29] V.M. Joshi, R.L. Magar, P.B. Throat, et al., Novel one-pot synthesis of 4H-chromene derivatives using amino functionalized silica gel catalyst, Chin. Chem. Lett. 25 (2014) 455-458.

    30. [30] D.C. Wang, Y.M. Xie, C. Fan, et al., Efficient and mild cyclization procedures for the synthesis of novel 2-amino-4H-pyran derivatives with potential antitumor activity, Chin. Chem. Lett. 25 (2014) 1011-1013.[30] D.C. Wang, Y.M. Xie, C. Fan, et al., Efficient and mild cyclization procedures for the synthesis of novel 2-amino-4H-pyran derivatives with potential antitumor activity, Chin. Chem. Lett. 25 (2014) 1011-1013.

    31. [31] B.D. Cui, W.Y. Han, Z.J. Wu, et al., Enantioselective synthesis of quaternary 3-aminooxindoles via organocatalytic asymmetric Michael addition of 3-monosubstituted 3-aminooxindoles to nitroolefins, J. Org. Chem. 78 (2013) 8833-8839.[31] B.D. Cui, W.Y. Han, Z.J. Wu, et al., Enantioselective synthesis of quaternary 3-aminooxindoles via organocatalytic asymmetric Michael addition of 3-monosubstituted 3-aminooxindoles to nitroolefins, J. Org. Chem. 78 (2013) 8833-8839.

    32. [32] B.D. Cui, J. Zuo, J.Q. Zhao, et al., Tandem Michael addition-ring transformation reactions of 3-hydroxyoxindoles/3-aminooxindoles with olefinic azlactones: direct access to structurally diverse spirocyclic oxindoles, J. Org. Chem. 79 (2014) 5305-5314.[32] B.D. Cui, J. Zuo, J.Q. Zhao, et al., Tandem Michael addition-ring transformation reactions of 3-hydroxyoxindoles/3-aminooxindoles with olefinic azlactones: direct access to structurally diverse spirocyclic oxindoles, J. Org. Chem. 79 (2014) 5305-5314.

  • 加载中
WeChat 扫一扫看文章
计量
  • PDF下载量:  0
  • 文章访问数:  1388
  • HTML全文浏览量:  18
文章相关
  • 发布日期:  2015-04-19
  • 收稿日期:  2015-01-20
  • 网络出版日期:  2015-04-03
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

/

返回文章

All Rights Reserved by the Chinese Chemical Society   中国化学会 版权所有 京ICP备05002797号

本系统由北京仁和汇智信息技术有限公司开发    技术支持: info@rhhz.net