Asymmetric synthesis and antiviral activity of novel chiral amino-pyrimidine derivatives

• Published in: Tetrahedron letters Vol. 59; no. 33; pp. 3179 - 3183
• Main Authors: Bai, Song, Liu, Shan, Zhu, Yunying, Wu, Qin
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.08.2018; Elsevier
• Subjects: Amino-pyrimidine derivatives; Antiviral activity; antiviral properties; Asymmetric synthesis; catalysts; chemical reactions; Chemistry; Chemistry, Organic; Cinchona; Cinchona alkaloid catalyst; enantiomers; enantioselectivity; organic compounds; Physical Sciences; Science & Technology; Tobacco mosaic virus; Asymmetric synthesis; Tobacco mosaic virus; Amino-pyrimidine derivatives; Antiviral activity; Cinchona alkaloid catalyst; ENANTIOSELECTIVE SYNTHESIS; BOND DONOR CATALYSTS; SAR; DOCKING; ORGANOCATALYSIS; PESTICIDES; ANTIMALARIAL ACTIVITY; INHIBITORS; HEME-BINDING; HYBRIDS
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2018.07.020

[Display omitted] •Employing chiral cinchona alkaloid-squaramide as catalyst.•Both enantiomers of the products can be obtained.•High yields and up to 98% ee.•The chiral products exhibit significant antiviral activity. By using a chiral cinchona alkaloid-squaramide catalyst, a series of both enantiomers of novel amino-pyrimidine derivatives can be obtained in an enantioselective three-component one-pot Mannich reaction with high yields and excellent enantioselectivities. In addition, these chiral derivatives were found to exhibit higher antiviral activities against tobacco mosaic virus (TMV) in vivo than the commercial agent ningnanmycin. In particular, chiral compounds (R)-4b and (R)-4e showed excellent antiviral activity against TMV at a concentration of 500 μg/mL, with a curative activity of 56.8% and 55.2%, respectively, a protection activity of 69.1% and 67.1%, respectively, and an inactivation activity of 91.5% and 94.3%, respectively. These values are superior to those of the agent ningnanmycin (which has curative, protective, and inactivation activities of 52.9%, 62.8%, and 90.4%, respectively). The antiviral mechanisms and enhanced antiviral activities of these chiral derivatives are interesting subjects for future investigation.