(R,S)-azolides as novel substrates for lipase-catalyzed hydrolytic resolution in organic solvents

Pei Yun Wang, Ying Ju Chen, An Chi Wu, Yi Sheng Lin, Min Fang Kao, Jin Ru Chen, Jyun Fen Ciou, Shau Wei Tsai*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

37 Scopus citations

Abstract

Azolides, that is, N-acylazoles, as versatile acylation reagents are well characterized in the literature, in which the azole structure can not only act as a better leaving group but also make the carbonyl carbon more electrophilic and susceptible to nucleophilic attack. It is therefore desirable to combine this unique property and lipase resolution ability in the development of a new resolution process for preparing optically pure carboxylic acids. With the Candida antarctica lipase B (CALB)-catalyzed hydrolysis of (R,S)-N- profenylazoles in organic solvents as the model system, (R,S)-N-profenyl-l,2,4- triazoles instead of their corresponding ester analogues were exploited as the best substrates for preparing optically pure profens, i.e., 2-arylpropionic acids. The structure-reactivity correlations for the (R,S)-azolides in water-saturated methyl tert-butyl ether (MTBE) at 45°C coupled with a thorough kinetic analysis were further employed for elucidating the rate-limiting formation of a tetrahedral adduct without C-N bond breaking or with moderate C-N bond breaking concerted with C-O bond formation in the acylation step. The advantages of easy substrate preparation, high enzyme reactivity and enantioselectivity, and easy recovery of the product and remaining substrate by aqueous extraction demonstrate the potential of using (R,S)-azolides as novel substrates for the enzymatic resolution process.

Original languageEnglish
Pages (from-to)2333-2341
Number of pages9
JournalAdvanced Synthesis and Catalysis
Volume351
Issue number14-15
DOIs
StatePublished - 2009

Keywords

  • (r,s)-azolides
  • (r,s)-profens
  • Candida antarctica lipase b
  • Hydrolytic resolution
  • Improved activity and enantioselectivity

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