Teresa Olejniczak

Lactones. Part 15: Synthesis of chiral spirolactones with a carane system—insect feeding deterrents

Abstract Starting from (+)-3-carene 1 several spirolactones with carane backbone were synthesized. δ-Hydroxy-γ-lactone 5 was obtained by acidic lactonization of a γ,δ-epoxy ester. Iodolactone 8 and bromolactone 9 were products of iodolactonization of γ,δ-unsaturated acid 7 and bromolactonization of γ,δ-unsaturated ester 3 respectively. The halo lactones were subjected to reductive dehalogenation with tributyltin hydride and dehydrohalogenation with DBU. The structures of the lactones obtained were confirmed by X-ray analysis and spectral data.

Synthesis and Fungistatic Activity of Bicyclic Lactones and Lactams against Botrytis cinerea, Penicillium citrinum, and Aspergillus glaucus

Six analogues of natural trans-4-butyl-cis-3-oxabicyclo[4.3.0]nonan-2-one (3) and three derivatives, 11, 12, and 13, of Vince lactam (10) were synthesized and tested as fungistatic agents against Botrytis cinerea AM235, Penicillium citrinum AM354, and six strains of Aspergillus. Moreover, bioresolution carried out by means of whole cell microorganisms and commercially available enzymes afforded opposite enantiomerically enriched (-) and (+) isomers of Vince lactam (10), respectively. The effect of compound structures and stereogenic centers on biological activity has been discussed. The highest fungistatic activity was observed for four lactones: 3, 4, 7, and 8 (IC50 = 104.6-115.2 μg/mL) toward B. cinerea AM235. cis-5,6-Epoxy-2-aza[2.2.1]heptan-3-one (13) indicated significant fungistatic activity (IC50 = 107.1 μg/mL) against Aspergillus glaucus AM211. trans-4-Butyl-cis-3-oxabicyclo[4.3.0]nonan-2-one (3) and trans-4-butyl-cis-3-oxabicyclo[4.3.0]non-7-en-2-one (7) exhibited high fungistatic activity (IC50 = 143.2 and 110.2 μg/mL, respectively) against P. citrinum AM354 as well.

Fungistatic Activity of Bicyclo[4.3.0]-γ-lactones

Five optically active and sixteen racemic lactones (nine of them new) of bicyclo[4.3.0]nonane structure were synthesized. IC(50) values for the following phytopathogens were determined: Aspergillus ochraceus AM 456, Fusarium culmorum AM 282, Fusarium oxysporum AM 13, Fusarium tricinctum AM 16. Effect of compound structures, especially stereogenic centers, on fungistatic activity has been discussed. The highest fungistatic activity was observed for trans-7,8-dibromo-cis-3-oxabicyclo[4.3.0]nonan-2-one (3c), IC(50) = 30.1 μg/mL (0.10 μM/mL), and cis-7,8-epoxy-cis-3-oxabicyclo[4.3.0]nonan-2-one (3b), IC(50) = 72.2 μg/mL (0.47 μM/mL), toward F. oxysporum AM 13.

Lactones 12. ☆: Enzymatic lactonization of γ,δ-epoxy esters by the apple fruit and Jerusalem artichoke bulb

Abstract The enzymatic lactonization of three acyclic γ,δ-epoxy esters (ethyl 3,7-dimethyl-4,5-epoxyoctanoate, ethyl 3,7,7-trimethyl-4,5-epoxyoctanoate, and ethyl 3,3,7-trimethyl-4,5-epoxyoctanoate) by apple fruit ( Malus silvestris ) and Jerusalem artichoke bulb ( Helianthus tuberosus L.) was investigated. The substrates were transformed into a mixture of isomeric δ-hydroxy-γ-lactones and γ-hydroxy-δ-lactones. The γ-lactones (yields ranging from 45–70%) predominated over δ-lactones (yields ranging from 8–40%). The composition of the product mixture depended on the structure of substrate as well as the biocatalyst. The enzymatic system in these biocatalysts also exhibited diastereoselectivity and enantioselectivity.

Biological Activity of Japanese Quince Extract and Its Interactions with Lipids, Erythrocyte Membrane, and Human Albumin.

The aim of the study was to determine in vitro biological activity of fruit ethanol extract from Chaenomeles speciosa (Sweet) Nakai (Japanese quince, JQ) and its important constituents (−)-epicatechin (EC) and chlorogenic acid (CA). The study also investigated the structural changes in phosphatidylcholine (PC) liposomes, dipalmitoylphosphatidylcholine liposomes, and erythrocyte membranes (RBC) induced by the extract. It was found that the extract effectively inhibits oxidation of RBC, induced by 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH), and PC liposomes, induced by UVB radiation and AAPH. Furthermore, JQ extract to a significant degree inhibited the activity of the enzymes COX-1 and COX-2, involved in inflammatory reactions. The extract has more than 2 times greater activity in relation to COX-2 than COX-1 (selectivity ratio 0.48). JQ extract stimulated growth of the beneficial intestinal bacteria Lactobacillus casei and Lactobacillus plantarum. In the fluorimetric method by means of the probes Laurdan, DPH and TMA-DPH, and 1H-NMR, we examined the structural changes induced by JQ and its EC and CA components. The results show that JQ and its components induce a considerable increase of the packing order of the polar heads of lipids with a slight decrease in mobility of the acyl chains. Lipid membrane rigidification could hinder the diffusion of free radicals, resulting in inhibition of oxidative damage induced by physicochemical agents. JQ extract has the ability to quench the intrinsic fluorescence of human serum albumin through static quenching. This report thus could be of huge significance in the food industry, pharmacology, and clinical medicine.

Lactones 7: 1. Enantioselective lactonization of racemic ethyl (5,5-dimethyl-2,3-epoxycyclohex-1-yl)acetate

Abstract Seven fungi strains were checked as biocatalysts of lactonization of ethyl (5,5-dimethyl-2,3-epoxycyclohex-1-yl)acetate. Two of them transformed the racemic substrate with high efficiency and enantioselectivity. Rhodotorula rubra transformed preferentially the (−) enantiomer of substrate, whereas Fusarium semitectum , the (+) one.

Microbial synthesis of a useful optically active (+)-isomer of lactone with bicyclo[4.3.0]nonane structure

Lactone 2a of a bicyclo[4.3.0]nonane structure is a good starting material for synthesis of many attractive compounds. Enantiomerically enriched (−)-(3aR,7aS)-lactone 2a is produced by whole cells of bacteria. In order to examine the impact of the absolute configuration on biological activity we evaluated the process affording the opposite isomer. To this purpose Candida pelliculosa ZP22 characterized by high dehydrogenase activity was used. The goal of presented work was to perform bioreactor scale microbial one-pot oxidation of diol with selected yeast strain C. pelliculosa ZP22 to obtain chiral (+)-(3aS,7aR)-lactone 2a. The idea was to influence on alcohol dehydrogenase activity by increasing the activity of pro-(+)-ADH and simultanously diminishing the activity of pro-(−)-ADH. The optimization of biotransformation conditions involved the manipulation of the nutritional and physical parameters. Selection of the optimal medium in order to improve yield and process enantioselectivity was based on a two-level factorial design methodology. We have also studied the relationship between microbial growth and biosynthesis of lactone 2a. Preparative oxidation of diol 3a (400 mg/L, 2.9 mM) catalyzed by C. pelliculosa ZP22 in an optimized conditions afforded enantiomerically enriched (+)-(3aS,7aR)-isomer of lactone 2a with the isolated yield (30%).

Improving of hydrolases biosythesis by solid-state fermentation of Penicillium camemberti on rapeseed cake

The study show usefulness of rapeseed cake, rich in fats and proteins byproduct generated after oil production, which may be used as a microbial medium for lipase and protease biosynthesis. Of 26 different filamentous fungi screened by solid-state fermentation, Penicillium camemberti AM83 was found to abundantly produce lipase and protease. Various process parameters were then optimized to maximize lipase and protease secretion, including carbon and nitrogen source, C/N ratio, metal ions, temperature, moisture content, initial pH, and inoculum size. Lipase production increased approximately 11.2-fold in solid-state cultures on rapeseed cake supplemented with lactose and calcium chloride, alkalinized to pH 8, hydrated to 80%, and inoculated with 1.2 × 106 spores/mL. Similarly, protease production increased approximately 8.4-fold in optimized cultures inoculated with 3.2 × 108 spores/mL, and grown on rapeseed cake with lactose and ammonium sulfate at pH 9 and moisture content 60%. The results highlight the potential economic value of solid-state fermentation on rapeseed cake to produce industrial hydrolases.

Antimicrobial activity of extracts and phthalides occurring in Apiaceae plants: Antimicrobial activity of phthalides

Apiaceae plants exhibit a broad spectrum of activities, for instance, antithrombotic, hypotensive, antioxidant, and insecticidal. They also provide a source of phthalides, which display antimicrobial activity. Considering the fact of rising resistance of both bacteria and fungi against commonly used antibiotics, developing of new naturally derived compounds is undeniably attractive approach. To our best knowledge, there are no other reviews concerning this subject in the literature. In view of above, an attempt to summarize an antimicrobial potential of isolated compounds and extracts from Apiaceae plants has been made, by specifying techniques of activity determination and methods of extraction. Techniques of antimicrobial activity evaluation are mainly based on bioautography, diffusion, and dilution methods. Therefore, we focused on in vitro data described in literature so far.

A Novel Approach for Microbial Synthesis of Enantiomerically Pure Whisky Lactones Based on Solid-State Fermentation

In this study, solid-state fermentation (SSF) was proposed as an alternative approach to obtain optically pure forms of one of the most common aroma compounds, whisky lactone. Filamentous fungi were used for enantioselective hydrolysis of a racemate of trans and cis whisky lactones, utilizing rapeseed cake as a growth medium. Among the tested fungi, Fusarium oxysporum AM13 and Papularia rosea AM17 were chosen for further studies. Various process parameters, including temperature, moisture content of solid media, and substrate concentration were optimized to maximize the efficiency of the kinetic resolution process. After optimization of the culture conditions (33 °C temperature, 60% moisture content, and substrate concentration of 3 mg/g oilseed cake), F. oxysporum AM13 resolved a mixture of trans-(+)-(4S,5R) and cis-(+)-(4R,5R) whisky lactones with enantiomeric excess (ee), ee > 99% and ee = 98%, respectively. This study presents an inexpensive and environmentally friendly method for the production of enantiomerically pure aroma lactones via the solid-state fermentation of oilseed cake. The results revealed that SSF is an effective method for acquiring highly valued and industrially demanded compounds with negligible economic cost.