Effect of chemical structure of benzofuran derivatives and reaction conditions on enantioselective properties of Aureobasidium pullulans microorganism contained in Boni Protect antifungal agent

Abstract

Bioorganic asymmetric reduction of carbonyl compounds is one of the most important fundamental and practical reactions for producing chiral alcohols. The stereoselective bioreduction of prochiral ketones of benzofuran derivatives in the presence of yeast‐like fungus Aureobasidium pullulans contained in the antifungal Boni Protect agent was studied. Biotransformations were carried out under moderate conditions in an aqueous and two‐phase system and without multiplication of the bioreagent. Despite similar chemical structure, each of the used ketone has been reduced with varying efficiency and selectivity. One of the reasons for these results is the presence of a whole set of oxidoreductases in A. pullulans cells that are sensitive to the smallest changes in the structure of prochiral substrate. The unsymmetrical methyl ketones were biotransformed with the highest selectivity. Aureobasidium pullulans microorganism is less effective in the reduction of unsymmetrical halomethyl ketones. The presence of a heteroatom in the alkyl group significantly decreases the selectivity of the process. Finally, as a result of the preferred hydride ion transfer from the dihydropyridine ring of the cofactor to the carbonyl double bond on the re side, secondary alcohols of the S and R configuration were obtained with moderate to high enantioselectivity (55‐99%).

Synthesis, Absolute Configuration, Antibacterial, and Antifungal Activities of Novel Benzofuryl β-Amino Alcohols

“…Due to the fact that, as an asymmetric reduction method, bioreduction is also in our field of interest [ 53 , 54 , 55 ], we decided to check the possibilities of the benzofuryl α -amino ketones reduction with the fungi of Saccharomyces cerevisiae and Aureobasidium pullulans species. Reduction with the use of baker’s yeast ( Saccharomyces cerevisiae ) is the best known and commonly used method of the microbiological chiral reduction [ 56 ].…”

“…Reduction with the use of baker’s yeast ( Saccharomyces cerevisiae ) is the best known and commonly used method of the microbiological chiral reduction [ 56 ]. In turn, the Boni Protect ® antimycotic agent containing living cells of Aureobasidium pullulans showed unusual catalytic abilities in the enantioselective reduction of various carbonyl compounds [ 53 , 55 ]. Three α -azole ketones, 1-(7-ethylbenzofuran-2-yl)-2-(1 H -imidazol-1-yl)ethanone ( 6 ), 1-(benzofuran-2-yl)-2-(1 H -1,2,4-triazol-1-yl)ethanone ( 9 ), and 1-(3,5-dimethylbenzofuran-2-yl)-2-(1 H -1,2,4-triazol-1-yl)ethanone ( 12 ) were selected for the microbiological reduction with the aforementioned reagents and the results are summarized in Table 1 .…”

“…The microbiological reduction was carried out in an aqueous medium using a phosphate buffer solution of pH = 7 in the presence of glucose as the energy source. The bioreduction with the use of A. pullulans was performed without and with additional substances (ethyl (9-antryl)glyoxylate (AMA-1), allyl alcohol, ethyl chloroacetate, cysteine) to improve enantioselectivity, i.e., additives which inhibit oxidoreductases (present in A. pullulans ) with a specific stereopreference [ 53 , 55 ]. The reduction of α -imidazole ketone 6 catalyzed by A. pullulans in the presence of cysteine gave the best results.…”

“…Reduction with the use of baker's yeast (Saccharomyces cerevisiae) is the best known and commonly used method of the microbiological chiral reduction [56]. In turn, the Boni Protect ® antimycotic agent containing living cells of Aureobasidium pullulans showed unusual catalytic abilities in the enantioselective reduction of various carbonyl compounds [53,55]. Three α-azole ketones, 1-(7-ethylbenzofuran-2-yl)-2-(1H- Due to the fact that, as an asymmetric reduction method, bioreduction is also in our field of interest [53][54][55], we decided to check the possibilities of the benzofuryl α-amino ketones reduction with the fungi of Saccharomyces cerevisiae and Aureobasidium pullulans species.…”

Microbial Synthesis of (S)- and (R)-Benzoin in Enantioselective Desymmetrization and Deracemization Catalyzed by Aureobasidium pullulans Included in the Blossom Protect™ Agent

“…Previously, we described an effective biotransformation of prochiral sp 2 hybridized compounds using the Boni Protect preparation as a catalyst. Chiral secondary alcohols and α- and β-hydroxy esters were obtained with high optical purity [ 36 , 37 , 38 , 39 ].…”