Fluorescent Chitosan Modified with Heterocyclic Aromatic Dyes.

Chitosan is a valuable, functional, and biodegradable polysaccharide that can be modified to expand its applications. This work aimed to obtain chitosan derivatives with fluorescent properties. Three heterocyclic aromatic dyes (based on benzimidazole, benzoxazole, and benzothiazole) were synthesized and used for the chemical modification of chitosan. Emission spectroscopy revealed the strong fluorescent properties of the obtained chitosan derivatives even at a low N-substitution degree of the dye. The effect of high-energy ultraviolet radiation (UV-C) on modified chitosan samples was studied in solution with UV-Vis spectroscopy and in the solid state with FTIR spectroscopy. Moreover, cytotoxicity towards three different cell types was evaluated to estimate the possibilities of biomedical applications of such fluorescent chitosan-based materials. It was found that the three new derivatives of chitosan were characterized by good resistance to UV-C, which suggests the possibility of using these materials in medicine and various industrial sectors.

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

In this study, we examined the Aureobasidium pullulans strains DSM 14940 and DSM 14941 included in the Blossom Protect™ agent to be used in the bioreduction reaction of a symmetrical dicarbonyl compound. Both chiral 2-hydroxy-1,2-diphenylethanone antipodes were obtained with a high enantiomeric purity. Mild conditions (phosphate buffer [pH 7.0, 7.2], 30 °C) were successfully employed in the synthesis of (S)-benzoin using two different methodologies: benzyl desymmetrization and rac-benzoin deracemization. Bioreduction carried out with higher reagent concentrations, lower pH values and prolonged reaction time, and in the presence of additives, enabled enrichment of the reaction mixture with (R)-benzoin. The described procedure is a potentially useful tool in the synthesis of chiral building blocks with a defined configuration in a simple and economical process with a lower environmental impact, enabling one-pot biotransformation.

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

A series of new benzofuryl α-azole ketones was synthesized and reduced by asymmetric transfer hydrogenation (ATH). Novel benzofuryl ß-amino alcohols bearing an imidazolyl and triazolyl substituents were obtained with excellent enantioselectivity (96-99%). The absolute configuration (R) of the products was confirmed by means of electronic circular dichroism (ECD) spectroscopy supported by theoretical calculations. Selected benzofuryl α-azole ketones were also successfully asymmetrically bioreduced by fungi of Saccharomyces cerevisiae and Aureobasidium pullulans species. Racemic and chiral ß-amino alcohols, as well as benzofuryl α-amino and α-bromo ketones were evaluated for their antibacterial and antifungal activities. From among the synthesized ß-amino alcohols, the highest antimicrobial activity was found for (R)-1-(3,5-dimethylbenzofuran-2-yl)-2-(1H-imidazol-1-yl)ethan-1-ol against S. aureus ATCC 25923 (MIC = 64, MBC = 96 µg mL-1) and (R)-1-(3,5-dimethylbenzofuran-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-ol against yeasts of M. furfur DSM 6170 (MIC = MBC = 64 µg mL-1). In turn, from among the tested ketones, 1-(benzofuran-2-yl)-2-bromoethanones (1-4) were found to be the most active against M. furfur DSM 6170 (MIC = MBC = 1.5 µg mL-1) (MIC-minimal inhibitory concentration, MBC-minimal biocidal concentration).

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

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%).

The application of safe for humans and the environment Polyversum antifungal agent containing living cells of Pythium oligandrum for biotransformation of prochiral ketones.

This report presents the whole-cell biotransformation of benzofuranyl-methyl ketone derivatives with the application of Polyversum antifungal agent containing Pythium oligandrum microorganism. Stereochemistry of the reduction of prochiral substrates was modified by the bioconversion conditions (concentration of reagents, a source of the carbon atom, biotransformation medium). In optimized conditions enantioselective process was noted. Secondary alcohols with excellent enantiomeric purity and high yields were obtained. The enantiomeric excess and conversion degree of 1-(benzofuran-2-yl)ethanol, 1-(7-ethylbenzofuran-2-yl)ethanol and 1-(3,7-dimethylbenzofuran-2-yl)ethanol were 99%/98.1%, 94%/94.4% and 99%/72.6%, respectively. In the presence of P. oligandrum, one of the enantiotopic hydrides of the dihydropyridine ring coenzyme is selectively transferred to a re side of the prochiral carbonyl group to give products with S configuration. This study demonstrates an inexpensive, eco-friendly approach in synthesis of optically pure benzofuran derivatives and can be an interesting alternative to organocatalysis. Furthermore, this method can be used in biotechnology processes due to its good chemical performance and a high degree of product isolation.

B-(3,3-difluoroallyl)diisopinocampheylborane for the enantioselective fluoroallylboration of aldehydes.

The fluoroallylboration of aldehydes with B-(3,3-difluoroallyl)diisopinocampheylborane, which was prepared via the hydroboration of 1,1-difluoroallene, provides chiral 2,2-gem-difluorinated homoallylic alcohols in good yields and 91-97% ee.

Asymmetric fluoroallylboration of aldehydes.

Contrary to previous reports, the homologation of benzyloxydifluorovinyllithium with bulky chiral iodomethylboronates readily provides a series of chiral γ,γ-difluoroallylboronates. Asymmetric fluoroallylboration of aldehydes with a 2-phenylbornane-2,3-diol-derived reagent provides gem-difluorinated homoallyl alcohols in good yields and 77-95% ee. Preparation of a chiral α-pyrone in >99% ee has also been described.

Fluoroallylboration-olefination for the synthesis of (Z)-4,4-difluoropent-2-enoates and 5,5-difluoro-5,6-dihydropyran-2-ones.

Horner-Wadsworth-Emmons (HWE) or Still-Gennari olefination of TBS-protected 3,3-difluoro-4-hydroxy-2-ones, derived from the difluoroallylboration of aldehydes, provides the Z-isomer of 4,4,-difluoropent-2-enoates. These, upon hydrolysis, followed by Yamaguchi cyclization, afford 5,5-difluoro-4-methyl-5,6-dihydro-α-pyrones in high yields.