Çolak, Nida Sezin; Kalay, Erbay; Şahin, Engin

Asymmetric bioreduction of aromatic and heteroaromatic ketones is an important process in the production of precursors of biologically active molecules. In this study, the bioreduction of aromatic and hetero aromatic prochiral ketones into optically active alcohols was investigated using Lactobacillus senmaizukei as a whole-cell catalyst, since whole-cells are less expensive than pure enzymes. The study indicates enantioselective bioreduction of various substituted aromatic ketones (1–16) to the corresponding (R)-and (S)-chiral secondary alcohols (1a–16a) in low to excellent enantioselectivity (6–94%) with good yields (58–95%). In addition, heteroaromatic prochiral ketones 1-(pyridin-2-yl)ethanone (17) and 1-(furan-2-yl)ethanone (18) were reduced to (R)-17a and (R)-18a in enantiopure form with excellent conversion (>99%) and yields. These findings show that L. senmaizukei is a very important biocatalyst for asymmetric reduction of both 6-membered and 5-member heteroaromatic methyl ketones. This method promising a green synthesis for the synthesis of biologically important secondary chiral alcohols in an environmentally friendly and inexpensive process.

AtıfScopus20·WoS20·OpenAlex19

İncele

Şahin, Engin

Candida zeylanoides P1 was investigated as whole cell biocatalyst for the bioreduction of biaryl prochiral ketones into chiral carbinols, which can be used as pharmaceutical intermediate. Bioreduction of different biaryl ketones was carried out to their corresponding chiral biaryl carbinols such as (S)-(4-chlorophenyl) (phenyl) methanol (2a), which can be used in the synthesis of L-cloperastine drug, with antitussive, antiepidemic activity and bronchial musculature relaxant characteristics, in gram scale, enantiopure form (>99%) and excellent yields. The selectivity of C. zeylanoides P1 in enantioselective reduction of biaryl ketones was not affected by the steric and electronic effects of substrates. The current method demonstrates an encouraging green chemistry approach for the production of biaryl secondary chiral alcohols of pharmaceutical importance in mild, inexpensive and environmentally friendly process. The present study has many benefits since this yeast biocatalyst were successfully applied bioreduction of structurally bulky prochiral substrates, which cannot be reducted by chemical catalysis.

AtıfScopus10·WoS9·OpenAlex10

İncele

Şahin, Engin

Aryl and heteroaryl chiral carbinols are useful precursors in the synthesis of drugs. Lactobacillus paracasei BD87E6, which is obtained from a cereal based fermented beverage, was investigated as whole cell biocatalyst for the bioreduction of different ketones (including aromatic, hetero-aromatic and fused bicyclic ketone) into chiral carbinols, which can be used as a pharmaceutical intermediate. The study shows that bioreduction of aryl, heteroaryl and fused bicyclic ketone (1–5) to their corresponding chiral carbinols (1a–5a) in excellent enantioselectivity (>99%) with high yields. This study gave the first example for an enantiopure production of (S)-6-chlorochroman-4-ol (3a), which has many antioxidant activity, by a biological method. For asymmetric bioreduction of other prochiral ketones, these results open way to use of L. paracasei BD87E6 as biocatalysts. Also, the present process shows a hopeful and alternative green synthesis for the production of enantiopure carbinols in a mild, inexpensive and environmentally friendly process.

AtıfScopus21·WoS18·OpenAlex20

İncele

Baydaş, Yasemin; Dertli, Enes; Şahin, Engin

Biocatalytic reduction is a very important field of research in synthetic organic chemistry. Herein, three different Lactic Acid Bacteria (LAB) strains were evaluated for their bioreduction potential using acetophenone as a model substrate. Among these strains, Lactobacillus kefiri P2 strain was determined as the best asymmetric reduction biocatalyst. Reaction optimization parameters such as reaction time, temperature, agitation speed and pH were systematically optimized using Lactobacillus kefiri P2 strain and model substrate acetophenone. Under these optimized reaction conditions, secondary chiral alcohols were obtained by bioreduction of various prochiral ketones with results up to 99% enantiomeric excess. In addition, the steric and electronic effects of substituents on enantioselectivity and conversion were evaluated. It has been shown that Lactobacillus kefiri P2 biocatalyst was an effective catalyst for asymmetric reduction. This method provides an environmentally friendly method for the synthesis of optically pure alcohols and an alternative approach to chemical catalysts.

AtıfScopus24·WoS22·OpenAlex22

İncele

Burmaoǧlu, Serdar; Çelik, Hülya; Göiksu, Süleyman; Maraş, Ahmet; Altundaş, Ramazan; Seçen, Hasan

The first total synthesis of (4E,6E)-1,7-bis(3,4-dihydroxyphenyl)-hepta-4, 6-dien-3-one and an alternative synthesis of (4E,6E)-1,7-bis(4-hydroxyphenyl)- hepta-4,6-dien-3-one, two natural diarylheptanoids, mainly based on Claisen-Schmidt condensation were described. The crucial steps of the syntheses were the condensation of OH-protected 4-aryl-2-butanones with OH-protected 3-aryl-acrylaldehydes by the in situ enamination and then deprotection of OH groups to give the corresponding natural diarylheptanoids.

AtıfScopus6·WoS5·OpenAlex7

İncele