Rasemik 1-fenil 1-propanolün lipaz katalizörlüğünde enantiyoseçimli esterleşme tepkimesiyle kinetik rezolüsyonu

• Main Author: Karadeniz, Fatma
• Other Authors: Mehmetoğlu, Ülkü, Biyoteknoloji
• Format: Master Thesis
• Language: Turkish
• Published: Biyoteknoloji Enstitüsü 2007
• Subjects: fenil; propanol; enantiyoseçimlilik; esterleşme; kinetik rezolüsyon; lipaz; liyofilize; mikrobiyal hücreler; enantioselectivity; phenyl; esterification; kinetic resolution; lipase; lyophilized microbial cells; Antarc*; Antarctica
• Online Access: https://hdl.handle.net/20.500.12575/78760

The enantiomerically pure chiral alcohols are building blocks in pharmaceutical compounds. In this study, resolution of (R,S)- 1-phenyl 1-propanol by enantioselective esterification with lipase-catalyzed was achieved. Derivates of 1-phenyl 1-propanol are used to cure of cancer cells and its another derivate (-)-Ephedrine HCI belongs to the group of medicines known as bronchodilators. The biological activities of enantiomeric pairs are greatly different. One enantiomer is usually provided the desired activity and the opposite enantiyomer may possess different and even harmful properties. Thus, it is important to produce enantiomerically pure 1-phenyl 1-propanol. In this work, the effects of enzyme source, acyl donor and solvent type, amount of added moleculer sieves, acyl donor /alcohol molar ratio, temperature and amount of enzyme were investigated on the enantioselective esterification of racemic 1-phenyl 1-propanol. Then, lyophilized microbial cells of Candida antarctica (Pseudozyma aphidis DSM 70725) was used as a biocatalyst in the esterification of (R,S)-1-phenyl 1-propanol. Microbial celles offer economical and technical benefits. To investigate the effect of lipase type, three different lipases were used (Novozym 435, Amano Lipase AK, Amano Lipase PS). Novozym 435 exhibited the highest enantioselectivity for resolution of (R,S)-1-phenyl 1-propanol. Novozym 435 was highyl selective toward (R)-1-phenyl 1-propanol, while (S)-1-phenyl 1-propanol remained unchanged. Enantioselectivity was determined by varying acyl length of fatty acid from C12 to C16, organic solvent with Log P values from 0.5 to 4.5 (THF, toluene, hexane, heptane, isooctane), acyl donor/alcohol molar ratio (1:1, 3:2, 2:1, 3:1), amount of added moleculer sieves (0-400 mg) and temperature (10-60oC). Moleculer sieves very commonly are used to remove the produced water as a drying agents in reaction mixture. Enantiomeric excess of substrate increased dramatically with increasing amount of moleculer sieves. And reaction time dropped at higher ...