On the enzymatic hydrolysis of methyl 2-fluoro-2-arylpropionates by lipases

• Published in: Tetrahedron Vol. 61; no. 33; pp. 8005 - 8012
• Main Authors: Bellezza, Francesca, Cipiciani, Antonio, Ricci, Giacomo, Ruzziconi, Renzo
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.08.2005; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Enzymatic hydrolysis; Fluorinated compounds; Lipases; Physical Sciences; Profens; Science & Technology; α-hydroxyacids; α-hydroxyacids; Lipases; Enzymatic hydrolysis; Profens; Fluorinated compounds; ENANTIOSELECTIVITY; alpha-hydroxyacids; ACIDS; ANALOGS; lipases; KINETIC RESOLUTION; CANDIDA-RUGOSA LIPASE; FLUORINE; fluorinated compounds; enzymatic hydrolysis; profens
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2005.06.007

The enzymatic hydrolysis of methyl 2-fluoro-2-arylpropionates was performed using lipases from Candida rugosa and Candida cylindracea (OF-360). A careful analysis of the reaction products revealed that racemic 2-hydroxy-2-arylpropionic acid and traces of 2-arylacrylic acid are formed, in addition to the expected 2-aryl-2-fluoropropionic acid. The presence of powerful electron-releasing groups in the aromatic ring of the substrate increase the amount of 2-hydroxypropionic acid. A mechanistic hypothesis has been formulated according to which the enzyme facilitates the elimination of fluoride ion from the hydrolysed acid with the formation of an α-carboxy-stabilized carbocation which provides 2-hydroxypropionic acids by nucleophilic attack of H 2O and 2-arylacrylic acids by a β-elimination process. Graphical Abstract