Browsing by Author "Mehmetoglu, Ulku"

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Optimization of the Asymmetric Synthesis of Chiral Aromatic Alcohol Using Freeze-Dried Carrots as Whole-Cell Biocatalysts
(Walter de Gruyter Gmbh, 2016) Kazici, Hilal Celik; Bayraktar, Emine; Mehmetoglu, Ulku
Asymmetric reduction of ketones is an important transformation in organic synthesis, because chiral carbinols are useful bioactive compounds. In this study, bioreduction of acetophenone (ACP) for production of enantiomerically pure (S)-1-phenyl-ethanol was investigated and freeze-dried carrots were used as a source of alcohol dehydrogenases (ADHs). However, production of product was investigated systematically using response surface methodology (RSM). Before RSM, the effects of the initial substrate concentration, reaction time, temperature and pH on the bioreduction were studied. The best results for enantiomeric excesses (ee) and conversion (c) were obtained with >99% and 58%, respectively, for the reaction time 48 h, initial substrate concentration 1 mm, reaction temperature 33 degrees C and pH 7. In the RSM, initial substrate concentration, concentration of plant cell, reaction time and stirring rate were chosen as independent variables. The predicted optimum conditions for a higher ee (>99%) and conversion (57.8%) were as follows: initial substrate concentration, 1 mm; concentration of plant cell, 25 g/l; reaction time, 52 h and stirring rate, 200 rpm. As a result of repeated experiments, the product was obtained as 0.6 mm at this optimum point and the values obtained demonstrated conformity with 0.578 mm value calculated by the model equation.
Production of Precursors for Anti-Alzheimer Drugs: Asymmetric Bioreduction in a Packed-Bed Bioreactor Using Immobilized D. Carota Cells
(Taylor & Francis inc, 2017) Kazici, Hilal Celik; Bayraktar, Emine; Mehmetoglu, Ulku
(S)-1-Phenylethanol derivatives, which are the precursors of many pharmacological products, have also been used as anti-Alzheimer drugs. Bioreduction experiments were performed in a batch and packed-bed bioreactor. Then, the kinetics constants were determined by examining the reaction kinetics in the batch system with free and immobilized carrot cells. Also, the effective diffusion coefficient (De) of acetophenone in calcium alginate-immobilized carrot cells was investigated. Kinetics constants for free cells, which are intrinsic values, are reaction rate V-max - 0.052 mmol L-1 min(-1), and constants of the Michaelis-Menten K-M = 2.31 mmol L-1. Kinetics constants for immobilized cells, which are considered apparent values, are V-max,V- app = 0.0407 mmol L-1 min(-1), K-M,K- app = 3.0472 mmol L-1 for 2 mm bead diameter, and V-max,V- app = 0.0453 mmol L-1 min(-1), K-M,K- app = 4.9383 mmol L-1 for 3 mm bead diameter. Average value of effective diffusion coefficient of acetophenone in immobilized beads was determined as 1.97 x 10(-6) cm(2) s(-1). Using immobilized carrot cells in an up-flow packed-bed reactor, continuous production of (S)-1-phenylethanol through asymmetric bioreduction of acetophenone was performed. The effects of the residence time and concentrations of substrate were investigated at pH 7.6 and 33 degrees C. Enantiomerically pure (S)-1-phenylethanol (ee > 99%) was produced with 75% conversion at 4-hr residence time.
Use of the Plant as Biocatalysts for Producing Enantiomerically Pure Seconder Alcohol
(Gazi Univ, Fac Engineering Architecture, 2015) Kazici, Hilal Celik; Mehmetoglu, Ulku
In this study, enantiomerically pure (S)-1-Phenylethanol was produced with bioreduction of acetophenone that the precursor of many pharmacological product. Derivatives of (S)-1-Phenylethanol (secondary alcohol) is used as the active ingredient of drug of anti alzheimer. Production of (S)-1-Phenylethanol was conducted with the asymmetric reduction reaction of acetophenone that biocatalyst for there action is enzyme of alcohol dehydrogenase (ADH). In this study, a variety of fruits and vegetables were used as source of enzyme (ADH) for reduction of the carbonyl group and ADH enzyme activities were determined of different plants (carrots, potatoes, grapes, radishes) for selection of suitable plant which it has the highest intra cellular enzyme activity. At the end of this election carrot has been considered as a biocatalyst which has highest ADH activity. The effects of size of biyocatalyst, source of enzyme, substrate concentration, temperature, reaction time, pH of there action and the amount of biocatalyst have been investigated on the production of (S)-1-Phenylethanol. It was found that ADH enzyme in fresh carrots catalysed the bioselective asymmetric reduction reactions at high conversion and high enantioselectively (>% 99 ee and 92% c), under the conditions of 2mM substrate concentration, 200 g/L biocatalyst concentration, 1,52 mm biyocatalyst size, reaction temperature 33 degrees C, pH=7 and 150 rpm agitation speed.