Dynamic Induction of Optical Activity in Triarylmethanols and Their Carbocations.

A series of artificial triarylmethanols has been synthesized and studied toward the possibility of exhibiting an induced optical activity. The observed chiroptical response of these compounds resulted from the chiral conformation of a triarylmethyl core. The chirality induction from a permanent chirality element to the liable triarylmethyl core proceeds as a cooperative and cascade process. The OH···O(R) and/or (H)O···HorthoC hydrogen bond formation along with the C-H···π interactions seem to be the most important factors that control efficiency of the chirality induction. The position of chiral and methoxy electron-donating groups within a trityl skeleton affects the amplitude of observed Cotton effects and stability of the trityl carbocations. In the neutral environment, the most intense Cotton effects are observed for ortho-substituted derivatives, which undergo a rapid decomposition associated with the complete decay of ECD signals upon acidification. From all of the in situ generated stable carbocations, only two exhibit intense Cotton effects in the low energy region at around 450 nm. The formation of carbocations is reversible; after alkalization, the ions return to the original neutral forms. Unlike most triarylmethyl derivatives known so far, in the crystal, the triarylmethanol, para-substituted with the chiral moiety, shows a propensity for a solid-state sorting phenomenon.

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).

Trityl-Containing Alcohols-An Efficient Chirality Transmission Process from Inductor to the Stereodynamic Propeller and their Solid-State Structural Diversity.

The cascade process of a dynamic chirality transmission from the permanent chirality center to the stereodynamic triphenylmethyl group has been studied for series of optically active trityl derivatives. The structural analysis, carried out with the use of complementary methods, enabled us to determine the mechanism of chirality transfer. The process of chirality transmission involves a set of weak but complementary electrostatic interactions. The induction of helicity in a trityl propeller is revealed by rising non-zero cotton effects in the area of trityl UV-absorption. The presence of an additional stereogenic center in close proximity to the trityl-containing stereogenic center significantly affects the sign and, to a lesser extent, magnitude of the respective cotton effects. Despite the bulkiness of the trityl, in the crystalline phase, the molecules under study strictly fill the space. In the crystal, molecules form aggregates stabilized by OH•••O hydrogen bonds. However, the presence of two trityl groups precludes formation of OH•••O hydrogen bonding. Additionally, the trityl group seems to be responsible for the formation of the solid solutions by e.g., racemates of trans- and cis-2-tritylcyclohexanol. Therefore, the trityl group acts as a supramolecular protective group, which in turn can be used in the crystal engineering.

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.