재사용 가능한 촉매들과 고성능 바이오촉매의 개발 및 응용

Abstract

1. Development of Polymer Supported Ruthenium Catalyst and Synthesis of (S)-Rivastigmine via Dynamic Kinetic ResolutionI explored the dynamic kinetic resolution of secondary alcohols using a polymer-supported ruthenium complex as the racemization catalyst. The polymer-bound ruthenium catalyst 15 was prepared by the coupling of polymer-bound benzoyl chloride 13 with [η4-Ph4C4CO]Ru(CO)3 14. This catalyst was several times recyclable for the racemization and DKR of 1-phenylethanol. It was applied to a DKR step for the synthesis of optically pure (S)-rivastigmine 23 which is a useful drug for the treatment of Alzheimer's disease and Parkinson's disease. The synthesis of rivastigmine thus was achieved in 5 steps from 3-hydroxyacetophenone with 57% overall yield and 97% ee.2. Activations and Reuses of α-Chymotrypsin by Magnetic NanoparticlesAn activity of enzyme is very low in organic media because of denaturation and aggregation of enzymes. To overcome this problem, I explored the role of iron oxide nanoparticles (IONs) as the additives for enhancing the enzymatic activity in organic media. It was found that IONs enhanced the specific activity of α-chymotrypsin by 100-fold if they were mixed with enzyme at 99:1 mass ratio. The activity enhancement appears to be due to the effect of water adsorbed on IONs. IONs-activated α-CT was applied to the synthsis of peptides which provided good yields. 3. Developments of Several Ionic Surfactant Coated Enzymes and fast Dynamic Kinetic Resolution with Ionic Surfactant Coated EnzymesI explored the DKR of α-alkyl propagyl alcohols using an ionic-surfactant-coated burkholderia cepacia lipase (ISCBCL) and a ruthenium-based racemization catalyst. ISCBCL was prepared by lyophilizing BCL (20%) in the presence of glycine (5%), ionic surfactant (25%) and dextrin (50%). The DKR reactions were performd with solutions containing substrate (0.3 mmol), Ru catalyst (5 mol%), IPA (1.5 eqiv.) and K2CO3 (1.0 equiv.) in toluene at 60 oC. Seven propagyl alcohols were subjected to DKR. All of them were successfully transformed into their acetates with good yields (91~97%) and good enantiopurities (84~99% ee).