Chemo-enzymatic synthesis and biological activity evaluation of propenylbenzene derivatives.

Propenylbenzenes, including isosafrole, anethole, isoeugenol, and their derivatives, are natural compounds found in essential oils from various plants. Compounds of this group are important and valuable, and are used in the flavour and fragrance industries as well as the pharmaceutical and cosmetic industries. The aim of this study was to develop an efficient process for synthesising oxygenated derivatives of these compounds and evaluate their potential biological activities. In this paper, we propose a two-step chemo-enzymatic method. The first step involves the synthesis of corresponding diols 1b-5b from propenylbenzenes 1a-5avia lipase catalysed epoxidation followed by epoxide hydrolysis. The second step involves the microbial oxidation of a diasteroisomeric mixture of diols 1b-5b to yield the corresponding hydroxy ketones 1c-4c, which in this study was performed on a preparative scale using Dietzia sp. DSM44016, Rhodococcus erythropolis DSM44534, R. erythropolis PCM2150, and Rhodococcus ruber PCM2166. Application of scaled-up processes allowed to obtain hydroxy ketones 1-4c with the following yield range 36-62.5%. The propenylbenzene derivatives thus obtained and the starting compounds were tested for various biological activities, including antimicrobial, antioxidant, haemolytic, and anticancer activities, and their impact on membrane fluidity. Fungistatic activity assay against selected strains of Candida albicans results in MIC50 value varied from 37 to 124 µg/mL for compounds 1a, 3a-c, 4a,b, and 5a,b. The highest antiradical activity was shown by propenylbenzenes 1-5a with a double bond in their structure with EC50 value ranged from 19 to 31 µg/mL. Haemolytic activity assay showed no cytotoxicity of the tested compounds on human RBCs whereas, compounds 2b-4b and 2c-4c affected the fluidity of the RBCs membrane. The tested compounds depending on their concentration showed different antiproliferative activity against HepG2, Caco-2, and MG63. The results indicate the potential utility of these compounds as fungistatics, antioxidants, and proliferation inhibitors of selected cell lines.

Trametes hirsuta as an Attractive Biocatalyst for the Preparative Scale Biotransformation of Isosafrole into Piperonal.

Piperonal is a compound of key industrial importance due to its attractive olfactory and biological properties. It has been shown that among the fifty-six various fungal strains tested, the ability to cleave the toxic isosafrole into piperonal through alkene cleavage is mainly found in strains of the genus Trametes. Further studies involving strains isolated directly from different environments (decaying wood, fungal fruiting bodies, and healthy plant tissues) allowed the selection of two Trametes strains, T. hirsuta Th2_2 and T. hirsuta d28, as the most effective biocatalysts for the oxidation of isosafrole. The preparative scale of biotransformation with these strains provided 124 mg (conv. 82%, isolated yield 62%) and 101 mg (conv. 69%, isolated yield 50.5%) of piperonal, respectively. Due to the toxic impact of isosafrole on cells, preparative scale processes with Trametes strains have not yet been successfully performed and described in the literature.

Stereoselective synthesis of whisky lactone isomers catalyzed by bacteria in the genus Rhodococcus.

Whisky lactone is a naturally occurring fragrance compound in oak wood and is widely used as a sensory additive in food products. However, safe and efficient methods for the production of its individual enantiomers for applications in the food industry are lacking. The aim of this study was to develop an efficient and highly stereoselective process for the synthesis of individual enantiomeric forms of whisky lactones. The proposed three-step method involves (1) column chromatography separation of a diastereoisomeric mixture of whisky lactone, (2) chemical reduction of cis-and trans-whisky lactones to corresponding syn-and anti-diols, and (3) microbial oxidation of racemic diols to individual enantiomers of whisky lactone. Among various bacteria in the genera Dietzia, Gordonia, Micrococcus, Rhodococcus, and Streptomyces, R. erythropolis DSM44534 and R. erythropolis PCM2150 effectively oxidized anti-and syn-3-methyl-octane-1,4-diols (1a-b) to corresponding enantiomerically pure cis-and trans-whisky lactones, indicating high alcohol dehydrogenase activity. Bio-oxidation catalyzed by whole cells of these strains yielded enantiomerically pure isomers of trans-(+)-(4S,5R) (2a), trans-(-)-(4R,5S) (2b), and cis-(+)-(4R,5R) (2d) whisky lactones. The optical density of bacterial cultures and the impact of the use of acetone powders as catalysts on the course of the reaction were also evaluated. Finally, the application of R. erythropolis DSM44534 in the form of an acetone powder generated the enantiomerically enriched cis-(-)-(4S,5S)-isomer (2c) from the corresponding syn-diol (1b). The newly developed method provides an improved approach for the synthesis of chiral whisky lactones.