Synlett 2018; 29(14): 1921-1925
DOI: 10.1055/s-0037-1609910
letter
© Georg Thieme Verlag Stuttgart · New York

Antiviral Bioactivity of Chiral β-Amino Acid Ester Derivatives Synthesized through a One-Pot, Solvent-Free Asymmetric Mannich Reaction

Song Bai  *
a   School of Chemical Engineering, Guizhou Institute of Technology, Guiyang 550003, P. R. of China   Email: Basonmail@163.com
b   Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, P. R. of China
,
Shan Liu
c   Drug identification Center of Guiyang Municipal Public Security Bureau, Guiyang Municipal Public Security Bureau, Guiyang 550081, P. R. of China
,
Yunying Zhu
a   School of Chemical Engineering, Guizhou Institute of Technology, Guiyang 550003, P. R. of China   Email: Basonmail@163.com
b   Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, P. R. of China
,
Kunhong Zhao
a   School of Chemical Engineering, Guizhou Institute of Technology, Guiyang 550003, P. R. of China   Email: Basonmail@163.com
,
Qin Wu
a   School of Chemical Engineering, Guizhou Institute of Technology, Guiyang 550003, P. R. of China   Email: Basonmail@163.com
b   Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, P. R. of China
› Author Affiliations
We are grateful for financial support from the National Natural Science Foundation of China (Grant No. 21602039), Natural Science Foundation of Guizhou Province, China (Grant No. Qian Ke He Ji Chu[2017]1066), the Opening Foundation of the Key Laboratory of Green Pesticide and Agricultural Bioengineering, the Ministry of Education, Guizhou University (Grant No. 2016GDGP0103), and the Research Center for Microreaction Engineering of Guizhou Colleges and Universities (Grant No. Qian Jiao He KY Zi[2015]339).
Further Information

Publication History

Received: 16 June 2018

Accepted after revision: 24 June 2018

Publication Date:
23 July 2018 (online)


Abstract

A series of both enantiomers of chiral β-amino acid ester derivatives containing a 4-(piperidin-1-yl)pyrimidine moiety was prepared in high yield and excellent enantioselectivity excess (up to >99% enantiomeric excess) using a chiral cinchona alkaloid thiourea catalyst under one-pot solvent-free conditions. Antiviral bioassay experimental results showed that some of the chiral products exhibited higher antiviral activities against tobacco mosaic virus (TMV) in vivo than the commercial antiviral agent ningnanmycin.

Supporting Information

 
  • References and Notes

    • 1a Villalba ML. Enrique AV. Higgs J. Castaño RA. Goicoechea S. Taborda FD. Gavernet L. Lick ID. Marder M. Bruno Blanch LE. Eur. J. Pharmacol. 2016; 774: 55
    • 1b Stachulski AV. Swift K. Cooper M. Reynolds S. Norton D. Slonecker SD. Rossignol JF. Eur. J. Med. Chem. 2016; 126: 154
    • 1c Khattab SN. Haiba NS. Asal AM. Bekhit AA. Amer A. Abdel-Rahman HM. El-Faham A. Bioorg. Med. Chem. 2015; 23: 3574
  • 2 Pawlak D. Schielmann M. Wojciechowski M. Andruszkiewicz R. Bioorg. Med. Chem. Lett. 2016; 26: 3586
    • 3a Karuvalam RP. Haridas KR. Nayak SK. Row TN. Rajeesh P. Rishikesan R. Kumari NS. Eur. J. Med. Chem. 2012; 49: 172
    • 3b Sharma S. Pandey AK. Shukla PK. Saxena AK. Bioorg. Med. Chem. Lett. 2011; 21: 6476
    • 3c Gellerman G. Pariente N. Paz Z. Shnaiderman A. Yarden O. J. Agric. Food Chem. 2009; 57: 8303
    • 4a Ma C. Cao R. Shi B. Li S. Chen Z. Yi W. Peng W. Ren Z. Song H. Eur. J. Med. Chem. 2010; 45: 1515
    • 4b Zhao M. Bi L. Wang W. Wang C. Baudy-Floc'H M. Ju J. Peng S. Bioorg. Med. Chem. 2006; 14: 6998
    • 5a Krecmerová M. Holý A. Andrei G. Pomeisl K. Tichý T. Brehová P. Masojídková M. Dracínský M. Pohl R. Laflamme G. J. Med. Chem. 2010; 86: 6825
    • 5b Sekiya K. Takashima H. Ueda N. Kamiya N. Yuasa S. Fujimura Y. Ubasawa M. J. Med. Chem. 2002; 45: 3138
  • 6 Fu X. Jiang S. Li C. Xin J. Yang Y. Ji R. Bioorg. Med. Chem. Lett. 2007; 17: 465
    • 7a Reddy AA. Prasad KR. J. Org. Chem. 2017; 82: 13488
    • 7b Ozeki M. Egawa H. Takano T. Mizutani H. Yasuda N. Arimitsu K. Kajimoto T. Hosoi S. Iwasaki H. Kojima N. Tetrahedron 2017; 73: 2014
    • 7c Zeng JL. Chachignon H. Ma JA. Cahard D. Org. Lett. 2017; 19: 1974
    • 7d Han J. Ai T. Nguyen T. Li G. Chem. Biol. Drug Des. 2008; 72: 120

      For reviews on β-amino acids, see the following:
    • 8a Cole DC. Tetrahedron 1994; 50: 9517
    • 8b Juaristi E. Quintana D. Escalante J. Aldrichimica Acta 1994; 27: 3
    • 8c Cardillo G. Tomasini C. Chem. Soc. Rev. 1996; 25: 117
    • 8d Enantioselective Synthesis of β-Amino Acids. Juaristi E. Wiley-VCH; Weinheim: 1997
    • 8e Abele S. Seebach D. Eur. J. Org. Chem. 2000; 1
    • 8f Cheng RP. Gellman SH. DeGrado WF. Chem. Rev. 2001; 101: 3219
    • 8g Liu M. Sibi MP. Tetrahedron 2002; 58: 7991
    • 8h Ma J.-A. Angew. Chem. Int. Ed. 2003; 42: 4290
    • 8i Weiner B. Szymański W. Janssen DB. Minnaard AJ. Feringa BL. Chem. Soc. Rev. 2010; 39: 1656
    • 8j Kim SM. Yang JW. Org. Biomol. Chem. 2013; 11: 4737
    • 9a Arend M. Westermann B. Risch N. Angew. Chem. Int. Ed. 2010; 37: 1044
    • 9b Sawa M. Morisaki K. Kondo Y. Morimoto H. Ohshima T. Chem. Eur. J. 2017; 23: 17022
    • 9c Wu H. An H. Mo SC. Kodadek T. Chem. Eur. J. 2017; 15: 3255
    • 9d You Y. Zhang L. Cui L. Mi X. Luo S. Angew. Chem. 2017; 56: 13814
    • 10a Lu N. Fang Y. Gao Y. Wei Z. Cao J. Liang D. Lin Y. Duan H. J. Org. Chem. 2017; 83: 1486
    • 10b Xin H. Miao L. Pham K. Zhang X. Yi W. Jasinski JP. Wei Z. J. Org. Chem. 2016; 81: 5362
    • 10c Li J. Du T. Zhang G. Peng Y. Chem. Commun. 2013; 49: 1330
    • 10d Bai S. Liang X. Song B. Bhadury PS. Hu D. Yang S. Tetrahedron: Asymmetry 2011; 42: 518
    • 10e Lou S. Dai P. Schaus SE. J. Org. Chem. 2008; 39: 9998
    • 11a Freedman TB. Cao X. Dukor RK. Nafie LA. Chirality 2003; 15: 743
    • 11b Nugroho AE. Morita H. J. Nat. Med. 2014; 68: 1
    • 12a Gooding GG. Jr. Hebert TT. Phytopathology 1967; 57: 1285
    • 12b Fan ZJ. Shi ZG. Zhang HK. Liu XF. Bao L. Ma L. Zuo XA. Zheng QX. Mi N. J. Agric. Food Chem. 2009; 57: 4279
    • 12c Song B. Zhang H. Wang H. Yang S. Jin L. Hu D. Lili Pang A. Xue W. J. Agric. Food Chem. 2005; 53: 7886
  • 13 General Experimental Procedure for the Preparation of (R)-4a Briefly, 4-methyl-6-(piperidin-1-yl)pyrimidin-2-amine (1, 0.30 mmol), benzaldehyde (2a, 0.30 mmol), dimethyl malonate (3a, 10 equiv, 3 mmol), and chiral catalyst Q4 (10 mol%) were added to capped vials at 60 °C and stirred for 36 h. After completion of the reaction, as observed by TLC, the mixture was directly purified by column chromatography on silica gel (hexane/EtOAc = 8:1), affording the product (R)-4a. However, the product (S)-4a was obtained using the Q5 catalyst. Enantiomeric excess of the product was determined by HPLC analysis using a Chiralpak IA column.