Kinetic Resolution of Pipecolic Acid Using Partially-Purified Lipase from Aspergillus niger

M. Christine Ng-Youn-Chen, Alessio N. Serreqi, Qingli Huang, Romas J. Kazlauskas

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Synthesis of biologically active peptides, alkaloids, and immunosuppresants such as FK506 requires enantiomerically-pure pipecolic acid (2-piperidinecarboxylic acid). We report an efficient kinetic resolution of pipecolic acid esters by enzyme-catalyzed hydrolysis. We screened commercially available hydrolases and identified crude lipase from Aspergillus niger (ANL) as the most enantioselective catalyst for the hydrolysis of (±)-methyl pipecolate, E = 20 ± 4 in favor of the (S)-enantiomer at pH7. Changing of the ester group to n-pentyl or n-octyl did not increase the enantioselectivity, while addition of an N-acetyl group decreased the enantioselectivity. Partial purification of ANL by fractional precipitation with ammonium sulfate (25-45 % saturation) increased the enantioselectivity to >100. A synthetic scale resolution of (±)-n-octyl pipecolate using this partially purified ANL gave (S)-(–)-pipecolic acid (93 % ee, 0.89 g) and (R)-(+)-pipecolic acid (97 % ee,1.20g). Further purification of ANL confirmed that the lipase (apparent molecular weight of 32 kDa), and not an impurity, was responsible for the enantioselective hydrolysis of octyl pipecolate.

Original languageEnglish (US)
Pages (from-to)2075-2081
Number of pages7
JournalJournal of Organic Chemistry
Volume59
Issue number8
DOIs
StatePublished - Apr 1 1994

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