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

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.

Key words

one-pot - solvent-free - chiral β-amino ester derivatives - Mannich reaction - antiviral bioactivity

• References and Notes

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• 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.