Synthesis of γ-hydroxy-α-(arylmethyl)carboxylic acids from lactones: pathway to a structural motif derived from lactic acid and amino acid analogs?

Abstract

Abstract Objective A synthetic pathway to γ-hydroxy-α-(arylmethyl)carboxylic acids starting from α-angelica lactone and γ-butyrolactone was investigated. These γ-hydroxycarboxylic acids resemble structural motifs of lactic acid and amino acids. The possibility of cocondensation with lactic acid towards functionalized poly(lactic acid)s was analyzed. Results The functional γ-hydroxycarboxylates sodium 4-hydroxy-2-((N-methylpyrazol-4-yl)methyl)pentanoate and sodium 4-hydroxy-2-(phenylmethyl)butanoate (2-benzyl-4-hydroxybutanoate) were synthesized in good yields as a proof of concept for the proposed reaction pathway. Additionally, sodium (E)-2-((N-methylpyrazol-4-yl)methylene)-4-oxopentanoate presenting an interesting structural motif was isolated. All products have been fully characterized by mass spectrometry, IR spectroscopy and 2D nuclear magnetic resonance (NMR) techniques. In contrast to the carboxylate anions, the corresponding carboxylic acids obtained after acidification were found to be unstable. The instability was analyzed by NMR experiments. With the help of diffusion ordered NMR spectroscopy, the cocondensation with lactic acid was elucidated. The reaction products were characterized as oligomers of pure lactic acid, while intramolecular condensation of the γ-hydroxycarboxylic acids prevents cocondensation with lactide.

Keywords

• Lactones
• α-Angelica lactone
• γ-Hydroxy-α-(arylmethyl)carboxylic acids
• Lactic acid
• Amino acid analogs
• Poly(lactic acid)