Developments of Kinetic Resolution Process for Preparing Stereo- and Regio-Isomers via Combinations of Azole and Enzyme Characteristics

Recently, we combined azole chemical characteristics with lipase enantioselective ability for developing the kinetic resolution process, in which excellent lipase performances were obtained when using (R,S)-N-acylazoles containing an aryl group to the α-chiral center as the substrate. This successful result has induced our motivation to submit the research proposal. In the following three years, we will focus on the topic of “Developments of lipase-catalyzed resolution platform for preparing chiral carboxylic acids and alcohols, as well as the azole regionisomers.”In the first-year project in order to find out the limitation and substrate range of the resolution platform, (R,S)-N-acylazoles without containing an aryl or aryloxy moiety to the α-chiral center, as well as containing a β-chiral center, are employed, in which effects of the acyl and leaving azole groups on lipase performances will be studied and compared with those previously obtained via kinetic and thermodynamic analysis. In the second year, (R,S)-azole-N-carboxylates are first synthesized from (R,S)-alcohols and then employed as the substrate for performing the lipase-catalyzed hydrolytic resolution. This approach is different from the conventional resolution using (R,S)-alcohol as an acyl acceptor, i.e. (R)- and (S)-alcohol in the acyl part of (R,S)-azole-N-carboxylate now acting as an acyl donor. This may act as an alternative in comparison with the conventional one to enhance the lipase enantioselectivity. In the third year, a new resolution platform for preparing azole-derivative regioisomers is proposed, in which (R,S)-azole-N-carboxylat containing azole tautomers are employed as the substrate for carrying out the lipase-catalyzed hydrolysis. It stresses that all chiral compounds and regioisomers play as important drugs or intermediates for the synthesis of drug, agrochemicals, or reagents in coordinate chemistry.

Project ID:PB10007-2278
External Project ID:NSC100-2221-E182-026-MY2