Chalcone-Derived Lactones: Synthesis, Whole-Cell Biotransformation, and Evaluation of Their Antibacterial and Antifungal Activity.

Four compounds with lactone moiety were synthesized from chalcone 1 in three- or four-step synthesis. γ-Bromo-δ-lactone 5 was the only product of bromolactonization of acid 4 whereas bromolactonization of ester 3, apart from lactone 5 also afforded its isomer 6 and two diastereoisomeric δ-hydroxy-γ-lactones 7 and 8. Lactone 8 was also obtained in 88% yield as a product of simultaneous dehalogenation and translactonization of γ-bromo-δ-lactone 5 by Penicillum frequentans AM 359. Chalcone-derived lactones 5-8 were subjected to the tests on antimicrobial activity and the results compared with activity of starting chalcone 1. Obtained lactones 5-8 in most cases limited the growth of tested bacterial and fungal strains. The highest activity was found for δ-hydroxy-γ-lactone 8 which completely inhibited the growth of Staphylococcus aureus, Fusarium graminearum, Aspergillus niger, and Alternaria sp. The introduction of lactone moiety into chalcone scaffold significantly improved antimicrobial activity of the compound: γ-bromo-δ-lactone 6 and δ-hydroxy-γ-lactone 8 were significantly stronger growth inhibitors of S. aureus and F. graminearum. In the case of the latter, a clear positive effect of the lactone function on the antifungal activity was also observed for γ-bromo-δ-lactone 5.

Methoxy-Substituted γ-Oxa-ε-Lactones Derived from Flavanones-Comparison of Their Anti-Tumor Activity In Vitro.

BACKGROUND: The study investigated four flavanone-derived γ-oxa-ε-lactones: a parent unsubstituted compound and its three derivatives with the methoxy group in positions 2', 4' and 8. Our objective was to find out if the introduction of the methoxy group into the aromatic ring affects in vitro anti-tumor potency of the investigated lactones. METHODS: Cytotoxic and pro-apoptotic effects were assessed with cytometric tests with propidium iodide, annexin V, and Western blot techniques. We also investigated potential synergistic potency of the tested lactones and glucocorticoids in canine lymphoma/leukemia cell lines. RESULTS: The tested flavanone-derived lactones showed anti-cancer activity in vitro. Depending on its location, the methoxy group either increased or decreased cytotoxicity of the derivatives as compared with the parent compound. The most potent lactone was the one with the methoxy group at position 4' of the B ring (compound 3), and the weakest activity was observed when the group was located at C-8 in the A ring. A combination of the lactones with glucocorticoids confirmed their synergy in anti-tumor activity in vitro. CONCLUSIONS: Methoxy-substituted flavanone-derived lactones effectively kill canine lymphoma/leukemia cells in vitro and, thanks to their synergistic action with glucocorticoids, may potentially be applied in the treatment of hematopoietic cancers.

Repellent and Antifeedant Activities of Citral-Derived Lactones against the Peach Potato Aphid.

Citral is well known for its antimicrobial, antifungal, and insecticidal activities. Natural sesquiterpene α-methylenelactones also exhibit a broad spectrum of biological activities. The aim of the study was to explore the effect of structural changes to citral molecules on citral behavior-modifying activity towards Myzus persicae. Specifically, the effects of the introduction of a γ-lactone moiety and methylene groups in α and γ positions of the lactone ring were investigated. The lactones were obtained in five-step (saturated lactone and γ-methylenelactone) or six-step (α-methylenelactone and α,γ-dimethylenelactone) syntheses from citral. The synthetic procedures and physical and spectral data of the lactones are presented. The settling behavior of freely moving aphids in choice and no-choice situations was monitored. The probing behavior of tethered M. persicae using the Electrical Penetration Graph (EPG) technique was also analyzed. Citral appeared a strong repellent and pre-ingestive and ingestive probing deterrent to M. persicae. The incorporation of a lactone moiety caused the loss of the repellent activity. α-Methylenelactone inhibited aphid settling and probing activities at pre-ingestive and ingestive phases. The saturated γ-lactone and α,γ-dimethylenelactone were the settling post-ingestive deterrents to M. persicae, which did not affect aphid probing activity. γ-Methylenelactone did not affect aphid behavior.

Synthesis and Antimicrobial Activity of Methoxy- Substituted γ-Oxa-ε-lactones Derived from Flavanones.

Six γ-oxa-ε-lactones, 4-phenyl-3,4-dihydro-2H-1,5-benzodioxepin-2-one (5a) and its five derivatives with methoxy groups in different positions of A and B rings (5b-f), were synthesized from corresponding flavanones. Three of the obtained lactones (5b,c,f) have not been previously described in the literature. Structures of all synthesized compounds were confirmed by complete spectroscopic analysis with the assignments of signals on 1H and 13C-NMR spectra to the corresponding atoms. In most cases, lactones 5a-f exerted an inhibitory effect on the growth of selected pathogenic bacteria (Escherichia coli, Bacillus subtilis, and Staphylococcus aureus), filamentous fungi (Fusarium graminearum, Aspergillus niger, and Alternaria sp.), and yeast (Candida albicans). The broadest spectrum of activity was observed for unsubstituted lactone 5a, which was particularly active against filamentous fungi and yeast. Lactones with methoxy groups in the 3' (5c) and 4' (5d) position of B ring were more active towards bacteria whereas lactone substituted in the 7 position of the A ring (5e) exhibited higher antifungal activity. In most cases, the introduction of lactone function increased the activity of the compound compared to its flavonoid precursors, chalcones 3a-e, and flavanones 4a-f.

ß-Thujone and Its Derivatives Modify the Probing Behavior of the Peach Potato Aphid.

Thujone is a natural biologically active monoterpene ketone component of essential oils of numerous plants. The aim of the study was to evaluate the effect of ß-thujone and ß-thujone derivatives bisulfite adduct, lactone, oxime, and lactam application on behavior of Myzus persicae (Sulz.) (Hemiptera: Aphididae) during probing and settling. The choice and no-choice tests (aphid settling and Electrical Penetration Graph (EPG), respectively) revealed that stereochemistry of thujone was important for biological activity (ß-thujone caused changes in aphid behavior while α-thujone did not) and that cyclopentane ring modifications and functional groups addition gave derivatives that possessed stronger and more durable deterrent effects. The most effective modification was the incorporation of a lactam moiety into the ß-thujone molecule. Application of ß-thujone lactam limited aphid settling for at least 24 h, caused restlessness in aphids and a delay or failure in reaching phloem phase by M. persicae. ß-Thujone lactam can be considered a deterrent of medium potency with activity expressed at preingestive phase of aphid probing. Other compounds did not restrain aphid stylet penetration in non-phloem tissues but slightly limited sap ingestion (lactone, oxime), and restrained aphid settling for a period of less than 24 h (ß-Thujone, bisulphite adduct, lactone).

Modulating effect of a new ester, 28-O-phosphatidylbetulin (DAPB), obtained from hen egg yolk lecithin and betulin on lymphocyte subsets and humoral immune response in mice.

Context: Leaf extracts of plants of the genus Betula have traditionally been used as diuretic, anti-rheumatic and diaphoretic preparations. One of the main active ingredients of Betula bark is betulin, lupane-type triterpene alcohol, with multiple biological activities. Objectives: The aim of this study was to investigate in vitro and in vivo immunomodulatory effects of a newly synthesized ester of betulin: 28-O-phosphatidylbetulin [28-O-(1,2-diacyl-sn-glycero-3-phospho)-betulin, DAPB] in comparison with betulin in mice. Materials and methods: Cytotoxic activity of DAPB or betulin was tested against non-cancer (D10.G4.1 and J774E.1) and cancer (GL-1; CL-1 and Jurkat) cell lines. The in vivo part assessed total lymphocyte count, weight ratio and subsets of lymphocytes in the lymphatic organs, and humoral immune response to sheep erythrocytes (SRBC). Results: In vitro assay showed that DAPB, contrary to betulin, had no antiproliferative activity. Exposure to four doses of DAPB increased the absolute count of immature CD4+CD8+ thymic cells as well as the percentage and absolute count of mature CD4+ and CD8+ thymocytes. DAPB enhanced the percentage or absolute count of CD3+ cells in spleen and lymph nodes with corresponding decrease in the percentage and/or absolute count of CD19+ cells. Both DAPB and betulin enhanced the percentage and absolute count of CD8+ lymphocytes in lymph nodes. In SRBC-immunized mice, betulin contrary to DAPB enhanced the number of splenocytes producing anti-SRBC antibodies (PFC). Both DAPB and betulin increased the level of total (IgM + IgG) and IgG titers. Conclusion: Despite the lack of cytotoxic activity, DAPB shows valuable immunomodulatory properties.

Microbial Asymmetric Functionalization of ß-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone.

Searching for the new anticancer compounds we prepared three new ß-cyclocitral-derived hydroxyl-γ-lactones by microbial hydroxylation of tetramethyl-substituted bicyclic γ-lactone. The substrate was transformed by the enzymatic system of filamentous fungi. Three out of fifteen strains were selected as effective biocatalysts (Fusarium culmorum AM10, Armillaria mellea AM296, Trametes versicolor AM536). The hydroxylation processes were not only regioselective but also stereoselective. The hydroxylation products of each secondary carbon atom in the cyclohexane ring were obtained by the application of the selected fungal strains. The Fusarium culmorum AM10 introduced the hydroxy function at C-3 and C-4, Armillaria mellea AM296 incorporated the hydroxy function at C-3 and C-5 and Trametes versicolor AM536 transformed the substrate to the mixture of C-3, C-4 and C-5 hydroxylactones. The hydroxylactones obtained were enantiomericaly enriched (ee values in the range 17⁻99%). The in vitro antiproliferative activities of the functionalization products were also evaluated. Regardless of the hydroxy substituent location all tested lactones exhibited similar, significant activity towards selected cancer cell lines (IC50 in the range 22.8⁻33.9 µg/mL).

Syntheses and cytotoxicity of phosphatidylcholines containing ibuprofen or naproxen moieties.

In this study, novel phosphatidylcholines containing ibuprofen or naproxen moieties were synthesized in good yields and high purities. Under the given synthesis conditions, the attached drug moieties racemized, which resulted in the formation of phospholipid diastereomers. The comperative studies of the cytotoxicity of ibuprofen, naproxen and their phosphatidylcholine derivatives against human promyelocytic leukemia HL-60, human colon carcinoma Caco-2, and porcine epithelial intestinal IPEC-J2 cells were carried out. The results of these studies indicated that phospholipids with NSAIDs at both sn-1 and sn-2 positions (15 and 16) were more toxic than ibuprofen or naproxen themselves, whereas 2-lysophosphatidylcholines (7 and 8) were less toxic against all tested cell lines. Phospholipids with NSAIDs at sn-1 and palmitic acid at sn-2 (9 and 10) were also less toxic against Caco-2 and normal cells (IPEC-J2).

Microbial Hydrolysis of Racemic ß-Aryl-γ-ethylidene-γ-lactones and Antifeedant Activity of the Products against Alphitobius diaperinus Panzer.

Hydrolysis of (±)-ß-aryl-γ-ethylidene-γ-lactones by fungal strain Aspergillus ochraceus AM370 afforded (−)-(S)-γ-ethylidene-γ-lactones 2a⁻d and (+)-(R)-γ-ketoacids 3a⁻d. Enantiomeric purity of the unreacted lactones was strictly related to a size of an aryl substituent at C-4 of γ-lactone ring, with the highest ee (77%) obtained for the (−)-(S)-γ-ethylidene-γ-lactone possessing unsubstituted benzene ring (2a) and the lowest one (15%) determined for the (−)-(S)-γ-ethylidene-γ-lactone with bulky 1,3-benzodioxole system (2d). Lactones 2a⁻d, both racemic and enantiomerically enriched, as well as products of their hydrolysis showed varying degrees of feeding deterrent activity against lesser mealworm, Alphitobius diaperinus Panzer, which depended on the structure of the compound and the developmental stage of the lesser mealworm. In the case of adults, more active were γ-lactones 2a⁻d, compared with ketoacids 3a⁻d. Only in the case of lactone 2a was the effect of configuration of stereogenic center on the activity found. Particularly strong deterrents against this stage (T > 180) were racemic and (−)-(S)-γ-ethylidene-γ-lactone with p-methoxysubstituted phenyl ring (2c).

Chemical composition, antimicromicrobial activity and insecticidal activity against the lesser mealworm Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae) of Origanum vulgare L. ssp. hirtum (Link) and Artemisia dracunculus L. essential oils.

BACKGROUND: Essential oils (EOs) from Artemisia dracunculus L. and Origanum vulgare L. ssp. hirtum were obtained and the qualitative and quantitative chemical composition of the extracts was investigated. The insecticidal activity of EOs against the larval stages of Alphitobius diaperinus (Panzer) was studied. Moreover, the antimicrobial activity of these oils against pathogens transmitted by this pest was also investigated. RESULTS: The obtained results indicate the possibility of using Greek oregano EO with a high content of carvacrol as a feed additive in poultry nutrition. The use of the Greek oregano oil at 1% (w/w) dose showed stronger reduction of body weight gain of stage IV larvae. Their body mass was only 10.92% of the control. Moreover, EOs from O. vulgare strongly inhibited the growth of tested bacterial strains as well as Candida albicans. CONCLUSION: Greek oregano EO may be a good alternative to antibiotic growth promoters and coccidiostats whose use in feeding farm animals has been prohibited since January 2006 under European Union directives. The introduction of O. vulgare L. ssp. hirtum EO into the premises of farm and poultry houses may help to improve sanitary conditions and control of the lesser mealworm inhabiting these buildings. © 2017 Society of Chemical Industry.

Regio- and enantioselective microbial hydroxylation and evaluation of cytotoxic activity of ß-cyclocitral-derived halolactones.

Three ß-cyclocitral-derived halolactones, which exhibit antifeedant activity towards storage product pests, were subjected to microbial transformation processes. Among the thirty tested strains of filamentous fungi and yeast, the most effective biocatalysts were Absidia cylindrospora AM336, Mortierella isabellina AM212 and Mortierella vinaceae AM149. As a result of regio- and enantioselective hydroxylation four new oxygenated derivatives were obtained. Regardless of the biocatalyst applied, the δ-iodo- and δ-bromo-γ-lactones were hydroxylated in an inactivated position C-5 of cyclohexane ring. The analogous transformation of chlorolactone was observed in Mortierella isabellina AM212 culture but in the case of two other biocatalysts the hydroxy group was introduced at C-3 position. All obtained hydroxylactones were enantiomerically pure (ee = 100%) or enriched (ee = 50%). The highest enantioselectivity of hydroxylation was observed for M. isabellina AM212. The cytotoxic activity of halolactones was also examined by WST-1 assay wherein tested compounds did not exhibit significant effect on the viability of tumor HeLa and normal CHO-K1 cells.

Syntheses and antiproliferative activities of novel phosphatidylcholines containing dehydroepiandrosterone moieties.

Dehydroepiandrosterone (DHEA) is a natural hormone with many beneficial properties including an anticancer activity. Unfortunately, DHEA is unstable in the body and exhibits cytotoxicity against healthy cells. In this study, a series of new phosphocholines containing DHEA at sn-1 and/or sn-2 positions were prepared. Succinic acid was used as a linker between the active drug and sn-glycero-3-phosphocholine. All the compounds were evaluated in vitro for their antiproliferative activities against four cell lines: Balb/3T3, HL-60, B16, and LNCaP. The results showed that phosphocholines with DHEA at sn-1 and/or sn-2 positions did not have cytotoxic effects on the normal cell line (Balb/3T3). Mixed-chain phospholipids with DHEA and fatty acid residues showed the highest activity against tumor cell lines. The most active compound, 11c, showed a moderate cytotoxic effect against the HL-60 and B16 cell lines.

Chemoenzymatic Synthesis of trans-ß-Aryl-δ-hydroxy-γ-lactones and Enzymatic Kinetic Resolution of Their Racemic Mixtures.

Two novel and convenient routes to obtain enantiomerically enriched trans-ß-aryl-δ-hydroxy-γ-lactones 5a-d with potential antifeedant and anticancer activity were developed. In the first method starting from corresponding enantiomers of γ,δ-unsaturated esters 4a-d derived from enzymatically resolved allyl alcohols 1a-d, both enantiomers of hydroxylactones 5a-d were synthesized with high enantiomeric excesses (73%-97%). Configurations of the stereogenic centers of the synthesized compounds were assigned based on the mechanism of acidic lactonization of esters 4a-d in the presence of m-chloroperbenzoic acid (m-CPBA). An alternative method for the production of optically active trans-ß-aryl-δ-hydroxy-γ-lactones 5a-d was lipase-catalyzed kinetic resolution of their racemic mixtures by transesterification with vinyl propionate as the acyl donor. The most efficient enzyme in the screening procedure was lipase B from Candida antarctica. Its application on a preparative scale after 6 h afforded unreacted (+)-(4S,5R,6S)-hydroxylactones 5a-d and (+)-(4R,5S,6R)-propionates 6a-d, most of them with high enantiomeric excesses (92%-98%). Resolution of lactone 5d with bulky 1,3-benzodioxol ring provided products with significantly lower optical purity (ee = 89% and 84% for hydroxylactone 5d and propionate 6d, respectively). The elaborated methods give access to both enantiomers of trans-ß-aryl-δ-hydroxy-γ-lactones 5a-d with the defined absolute configurations of stereogenic centers, which is crucial requirement for the investigations of relationship: spatial structure-biological activity.

Dehalogenation Activity of Selected Fungi Toward δ-Iodo-γ-Lactone Derived from trans,trans-Farnesol.

Time-course of biotransformation of racemic trans-4-((E)-4',8'-dimethylnona-3',7'-dien-1-yl)-5-iodomethyl-4-methyldihydrofuran-2-one (1) in fungal and yeast cultures was investigated. In these conditions, the substrate 1 was enantioselectively dehalogenated yielding 4-((E)-4',8'-dimethylnona-3',7'-dien-1-yl)-4-methyl-5-methylenedihydrofuran-2-one (2) and its structure was established based on the spectroscopic data. The most effective biocatalyst used was Didymosphaeria igniaria, which catalyzed the process with highest rate and enantioselectivity (ee of product = 76%). The antiproliferative activity of δ-iodo-γ-lactone 1, product of its biotransformation 2, and starting substrate (farnesol) were evaluated toward two cancer cell lines: A549 (human lung adenocarcinoma) and HL-60 (human promyelocytic leukemia).

Chemo-Enzymatic Synthesis of Optically Active γ- and δ-Decalactones and Their Effect on Aphid Probing, Feeding and Settling Behavior.

The enantiomerically enriched γ- and δ-decalactones (4a and 4b) were prepared from corresponding racemic primary-secondary 1,4- and 1,5-diols (1a and 1b), as products of enzymatic oxidation catalyzed by different alcohol dehydrogenases. The results of biotransformations indicated that the oxidation processes catalyzed by alcohol dehydrogenase (HLADH), both isolated from horse liver and recombinant in Escherichia coli, were characterized by the highest degree of conversion with moderate enantioselectivity of the reaction. Useful, environmentally friendly extraction procedure of decalactones (4a and 4b) based on hydrodistillation using a Deryng apparatus was developed. Both racemic lactones (4a and 4b), as well as their enantiomerically enriched isomers, were tested for feeding deterrent activity against Myzus persicae. The effect of these compounds on probing, feeding and settling behavior of M. persicae was studied in vivo. The deterrent activity of decalactones (4a and 4b) against aphids depended on the size of the lactone ring and the enantiomeric purity of the compounds. δ-Decalactone (4b) appeared inactive against M. persicae while γ-decalactone (4a) restrained aphid probing at ingestional phase. Only (-)-(S)-γ-decalactone (4a) had strong and durable (i.e. lasting for at least 24 hours) limiting effect, expressed at phloem level.

Lactones 46. Synthesis, antifeedant and antibacterial activity of γ-lactones with a p-methoxyphenyl substituent.

BACKGROUND: Lactones are well known for their biological activity. Grosheimin and repin are potent deterrents against storage pests. The unsaturated lactones have exhibited a wide spectrum of antibacterial activity. In our study we focused on the synthesis and evaluation of the biological activity of anisaldehyde derivatives containing lactone function. RESULTS: Four new lactones were synthesized in one-step reductive dehalogenation or dehydrohalogenation reactions. These compounds, together with halolactones synthesized earlier, were tested for their antifeedant activity towards Sitophilus granaries, Trogoderma granarium and Tribolium confusum. The results of the tests showed that the highest activity, comparable with that of azadirachtin, towards all tested pests (total coefficient of deterrence 143.3-183.9) was observed for lactone with a vinyl substituent. The antibacterial activity of these compounds was also evaluated. The most potent lactone was active towards gram-positive bacteria strains. CONCLUSIONS: The results of biological tests showed that halogen atom removal significantly increased the antifeedant properties of γ-lactones with a p-methoxyphenyl substituent. Unsaturated lactones are most promising in the context of their possible industrial application as crop protection agents. Further structural modifications of lactones with aromatic rings are needed to find important structural factors increasing the antibacterial activity.

Systemic deterrence of aphid probing and feeding by novel ß-damascone analogues.

ß-Damascone appeared a weak attractant close to not active to Myzus persicae, but modifications of its structure caused the avoidance of treated leaves by aphids during settling and reluctance to probe in simple choice- and no-choice experiments in previous studies. Here, the electrical penetration graph (EPG) technique, which allows monitoring of aphid probing within plant tissues, was applied to explore the biological background and localisation in plant tissues of the deterrent activities of ß-damascone and its analogues. Activity of ß-damascone and ß-damascone-derived compounds depended on their substituents, which was manifested in the variation in the potency of the behavioural effect and differences in aphid probing phases that were affected. ß-Damascone appeared a behaviourally inactive compound. The moderately active ß-damascone ester affected aphid activities only during the phloem phase. The highly active deterrents-dihydro-ß-damascol, ß-damascone acetate, δ-bromo-γ-lactone, and unsaturated γ-lactone-affected pre-phloem and phloem aphid probing activities. The most effective structural modification that evoked the strongest negative response from M. persicae was the transformation of ß-damascone into δ-bromo-γ-lactone. The behavioural effect of this transformation was demonstrated in frequent interruption of probing in peripheral tissues, which caused repeated failures in finding sieve elements, and reduction in the ingestion time during the phloem phase in favour of watery salivation. The inhibition of aphid probing at both the pre-phloem and phloem levels reveals the passage of the compounds studied through the plant surface and their distribution within plant tissues in a systemic way, which may reduce the risk of the transmission of non-persistent and persistent viruses.

Synthesis and Antifeedant Activity of Racemic and Optically Active Hydroxy Lactones with the p-Menthane System.

Two racemic and two enantiomeric pairs of new δ-hydroxy-γ-lactones based on the p-menthane system were prepared from racemic and optically active cis- and trans-piperitols. The Johnson-Claisen rearrangement of the piperitols, epoxidation of the γδ-unsaturated esters, and acidic lactonization of the epoxy esters were described. The structures of the compounds were confirmed spectroscopically. The antifeedant activities of the hydroxy lactones and racemic piperitone were evaluated against three insect pests: lesser mealworm, Alphitobius diaperinus (Panzer); Colorado potato beetle, Leptinotarsa decemlineata (Say); and peach-potato aphid, Myzus persicae (Sulz.). The chemical transformation of piperitone by the introduction of a lactone moiety and a hydroxy group changed its antifeedant properties. Behavioral bioassays showed that the feeding deterrent activity depended on the insect species and the structure of the compounds. All hydroxy lactones deterred the settling of M. persicae. Among chewing insects, the highest sensitivity showed A. diaperinus adults.

Positional analysis of phosphatidylcholine and phosphatidylethanolamine via LC with a charged aerosol detector.

A new method for the positional analysis of egg yolk phospholipids (PLs) (phosphatidylcholine-PC, phosphatidylethanolamine-PE) using liquid chromatography with charge aerosol detector (CAD) is described. The method is based on six-step procedure: 1) extraction of phospholipids from tissue sample, 2) separation of lipid classes by solid phase extraction (SPE), 3) complete regiospecific hydrolysis of phospholipids by phospholipase A2 (PLA2), 4) separation of reaction products (fatty acids from sn-2 position and 1-acyl lysophospholipids) by SPE, 5) chemical hydrolysis of 1-acyl lysophospholipids, and 6) analysis of obtained fatty acids by LC with charge aerosol detection (CAD). Total time of enzymatic hydrolysis of PLs ranged from 10-30min. The reaction products were separated by SPE in three-step gradient elution procedure. Chloroform: methanol mixtures were used as eluents to obtain pure fractions of FAs from sn-2 position of PL and 1-acyl lysoPL (chemically hydrolyzed to FAs). FAs were separated by reversed-phase LC using a gradient elution and detected using CAD detector. This combination enables determination of all fatty acids in a single analysis, and without the sample derivatization. The method was optimized and the response of CAD, linearity, precision and sensitivity of the method were studied.

Microbial transformations of halolactones with p-menthane system.

Biologically active piperitone-derived racemic iodo-, bromo- and chlorolactones (1-3) were transformed with the use of microbial enzymatic systems. Four strains of filamentous fungi Absidia glauca AM254, Absidia cylindrospora AM336, Mortierella vinaceae AM149 and Nigrospora oryzae AM8 transformed halolactones (1-3) to four new halohydroxylactones (4-7). In all biotransformations the hydroxy group was incorporated in inactivated methine carbon atom at isopropyl substituent. In N. oryzae AM8 culture the bromolactone with additional hydroxy group in α-position, relative to CO bond in γ-lactone ring, was also formed as a product. The structures of new compounds were established on the basis of spectral data.