Conversion of ( + )-Carvone by Pseudomonas ovalis,Strain 6-1 (1)

The conversion of (+)-carvone by Pseudomonas ovalis, strain 6-1, was investigated. (+)-Carvone was found to be reduced to (?)-isodihydrocarvone, (?)-isodihydrocarveol, (?)-neoisodihydrocarveol, (?)-dihydrocarvone, (?)-neodihydrocarveol, and (+)-dihydrocarveol, of which the former three were the major products.

From these results, it was postulated that Pseudomonas ovalis, strain 6-1, has different pathways for (+)-carvone and (?)-carvone, respectively; (+)-carvone is converted via (?)- isodihydrocarvone to (?)-isodihydrocarveol and (?)-neoisodihydrocarveol, whereas (?)- carvone is converted via (+)-dihydrocarvone to (?)-dihydrocarveol.

Stereochemical structures of four isomers of dihydrocarveols were also discussed on the basis of PMR results.     

Conversion of (−)-Carvone and (+)-Carvone by a Strain of Aspergillus niger

The conversion of (?)-carvone and (+)-carvone by a strain of Aspergillus niger was studied as one of the series of biochemical reduction of terpenes.

(?)-Carvone was found to be reduced essentially to (+)-neodihydrocarveol, although (+)-dihydrocarvone and (+)-isodihydrocarvone were also formed in small amounts, whereas (+)-carvone was converted to (?)-isodihydrocarvone, (?)-isodihydrocarveol, (?)-neoisodihydrocarveol, (?)-dihydrocarvone, (?)-neodihydrocarveol, and (+)-dihydrocarveol, of which the former three were the major products.

The metabolic pathways for (?)-carvone and (+)-carvone by the strain of Aspergillus niger are discussed and the results on microbial and chemical reductions of carvone and dihydrocarvone are summarized.     

X-Ray and IR-Studies on the Dehydrated Fish Flesh

Many actinomycetes, newly isolated from soil, converted (?)-carvone to either (?)-trans-carveol or (?)-cis-carveol or to a mixture of both compounds, and known metabolic products, such as (+)-dihydrocarvone, (+)-isodihydrocarvone, (+)-neodihydrocarveol, (?)-dihydrocarveol, (+)-isodihydrocarveol and (+)-neoisodihydrocarveol.

Identification of the metabolic products and the metabolic pathways of (?)-carvone were described in a strain of Streptomyces, A-5–1 and a strain of Nocardia, 1-3-11. A summary shows the reaction mechanism pattern of (?)-carvone conversion by actinomycetes.     

Studies on the Reduction of Terpenes with Sodium in Aqueous-ammonia

On reduction of (?)-menthone by various methods, generally, a mixture of (?)-menthol and (+)-neomenthol has been obtained. In the present work, it is found that (?)-menthol can be prepared almost quantitatively from (?)-menthone by treatment with sodium in aqueous-ammonia.     

Biotransformations. XIX. Reduction of some terpenic ketones by means of immobilized cells of rhodotorula mucilaginosa

Reduction of (?)-menthone ((?)- 1 ), (+)-(R)-methyl-α-campholenone ((+)- 2 ), (+)-carvone ((+)- 3 ), and eucarvone ( 4 ) was carried out by means of cells of the Rhodotorula mucilaginosa species immobilized in polyacrylamide gel. Alcohols with the (S)-configuration, (+)-neomenthol ((+)- 1a ), (+)-(R)-methyl-α-campholenol ((+)- 2a ), (?)-neoisodihydrocarveol ((?)- 3a ), dihydroeucarveol ((?)- 4a ), and small amounts of (?)-dihydroeucarvone ((?)- 5 ), were obtained. The cells of R. mucilaginosa maintained after this reaction ability to reduce standard acetophenone to (?)- 1 -phenyl- 1 -ethanol.     

Inhibition by menthol and its related chemicals of compound action potentials in frog sciatic nerves

AimsTransient receptor potential (TRP) vanilloid-1 (TRPV1) and melastatin-8 (TRPM8) channels play a role in transmitting sensory information in primary-afferent neurons. TRPV1 agonists at high concentrations inhibit action potential conduction in the neurons and thus have a local anesthetic effect. The purpose of the present study was to know whether TRPM8 agonist menthol at high concentrations has a similar action and if so whether there is a structure–activity relationship among menthol-related chemicals.Main methodsCompound action potentials (CAPs) were recorded from the frog sciatic nerve by using the air-gap method.Key findings(?)-Menthol and (+)-menthol concentration-dependently reduced CAP peak amplitude with the IC₅₀ values of 1.1 and 0.93 mM, respectively. This (?)-menthol activity was resistant to non-selective TRP antagonist ruthenium red; TRPM8 agonist icilin did not affect CAPs, indicating no involvements of TRPM8 channels. p-Menthane, (+)-limonene and menthyl chloride at 7–10 mM minimally affected CAPs. On the other hand, (?)-menthone, (+)-menthone, (?)-carvone, (+)-carvone and (?)-carveol (in each of which chemicals OH or O group was added to p-menthane and limonene) and (+)-pulegone inhibited CAPs with extents similar to that of menthol. 1,8-Cineole and 1,4-cineole were less effective while thymol and carvacrol were more effective than menthol in inhibiting CAPs.SignificanceMenthol-related chemicals inhibited CAPs and were thus suggested to exhibit local anesthetic effects comparable to those of lidocaine and cocaine as reported previously for frog CAPs. This result may provide information to develop local anesthetics on the basis of the chemical structure of menthol.     

Biotransformation of (+)-carvone and (−)-carvone using human skin fungi: A green method of obtaining fragrances and flavours

The synthesis of optically pure compounds is increasingly in demand among the pharmaceutical, fine chemical and agro-food industries, while the importance of chirality in the activity and biological properties of many compounds has previously been established. The aim of the present study was therefore to evaluate the biotransformation capacities of (+)-carvone and (?)-carvone using the fungi Scolecobasidium sp, three lines of Cladosporium sp, Phoma sp, Aureobasidium sp and Epicoccum sp, all obtained from human skin. The seven fungi evaluated were capable of hydrogenating the activated alkene, followed by the reduction of ketone to chiral alcohol, with conversions between 9.5 and 100%, and with diastereomer excess (d.e.) of over 89% of dihydrocarveol when (+)-carvone was used as a substrate. These results demonstrate that the filamentous fungi of human skin are potential biocatalytic tools for obtaining chiral alcohols.     

Biotransformation of electron-poor alkenes by yeasts: Asymmetric reduction of (4S)-(+)-carvone by yeast enoate reductases

Within the framework of a large-scale screening carried out on 146 yeasts of environmental origin, 16 strains (11% of the total) exhibited the ability to biotransform (4S)-(+)-carvone. Such positive yeasts, belonging to 14 species of 6 genera (Candida, Cryptococcus, Hanseniaspora, Kluyveromyces, Pichia and Saccharomyces), were thus used under different physiological state (growing, resting and lyophilised cells). Yields (expressed as% of biotransformation) varied from 0.14 to 30.04%, in dependence of both the strain and the physiological state of the cells. Products obtained from reduction of (4S)-(+)-carvone were 1S,4S- and 1R,4S-dihydrocarvone, (1S,2S,4S)-, (1S,2R,4S)- and (1R,2S,4S)-dihydrocarveol. Only traces of (1R,2R,4S)-dihydrocarveol were observed in a few strains. As far as the stereoselectivity of the biocatalysis, with the sole exception of a few strains, the use of yeasts determined the prevalent accumulation of 1S,4S-isomers [(1S,4S)-dihydrocarvone + (1S,2S,4S)-dihydrocarveol + (1S,2R,4S)-dihydrocarveol].The addition of glucose (acting as auxiliary substrate for cofactor-recycling system) to lyophilised yeast cells determined a considerable increase of biocatalytic activity: in particular, two strains showed a surprising increase of the% of biotransformation of (4S)-(+)-carvone (to values >98%).     

Integration of metabolomics and in vitro metabolism assays for investigating the stereoselective transformation of triadimefon in rainbow trout

Triadimefon is a systemic agricultural fungicide of the triazole class whose major metabolite, triadimenol, also a commercial fungicide, provides the majority of the actual fungicidal activity, i.e., inhibition of steroid demethylation. Both chemicals are chiral: triadimefon has one chiral center with two enantiomers while its enzymatic reduction to triadimenol produces a second chiral center and two diastereomers with two enantiomers each. All six stereoisomers of the two fungicides were separated from each other using a chiral BGB‐172 column on a GC‐MS system so as to follow stereospecificity in metabolism by rainbow trout hepatic microsomes. In these microsomes the S‐(+) enantiomer of triadimefon was transformed to triadimenol 27% faster than the R‐(?) enantiomer, forming the four triadimenol stereoisomers at rates different from each other. The most fungi‐toxic stereoisomer (1S,2R) was produced at the slowest rate; it was detectable after 8 h, but below the level of method quantitation. The triadimenol stereoisomer ratio pattern produced by the trout microsomes was very different from that of the commercial triadimenol standard, in which the most rat‐toxic pair of enantiomers (known as “Diastereomer A”) is about 85% of the total stereoisomer composition. The trout microsomes produced only about 4% of “Diastereomer A”. Complementary metabolomic studies with NMR showed that exposure of the separate triadimefon enantiomers and the racemate to rainbow trout for 48 h resulted in different metabolic profiles in the trout liver extracts, i.e., different endogenous metabolite patterns that indicated differences in effects of the two enantiomers. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Synthesis of Dihydrohelminthosporic Acids and their Plant Growth-promoting Activity

In the reduction of (?)-isomenthone with sodium in aqueous ammonia, it was found that the reduction product gives a mixture consisting of 75.5% of (?)-isomenthol (a,e,e), 9.5% of (+)-menthol (e,e,e) and 8.6% of (?)-neoisomenthol (a,a,e). From this fact, it might be concluded that this reduction is stereospecific for isomenthone and is mechanistically different from reduction with sodium and alcohol.     

Biosynthesis of carvone in Mentha spicata

Degradation of, and measurement of isotope ratios in, (?)-carvone that had been biosynthesized in Mentha spicata from ³H- and ¹⁴C-labelled geraniol and mevalonate indicate that (a) oxidation of limonene or its biogenetic equivalent to form carvone involves shift of the endocyclic double bond; (b) (+)-limonene and (?)-carvone are biogenetically related and are probably formed on divergent pathways from a common intermediate; and (c) the exocyclic double bond of carvone is not formed regiospecifically. These results enable the mechanisms for the introduction of the carbonyl group and for the formation of the isopropenyl side-chain to be delimited.     

Effectiveness of monoterpenes and phenylpropenes on Sitophilus oryzae L. (Coleoptera: Curculionidae) in stored wheat

Six monoterpenes, ((?)-citronellal, p-cymene, (?)-menthone, α-pinene, α-terpinene and (?)-terpinen-4-ol) and two phenylpropenes, (trans-cinnamaldehyde and eugenol) were tested for their insecticidal activity against the rice weevil, Sitophilus oryzae under laboratory conditions. The bioassays were carried out on wheat at the concentrations of 0.5, 1.0 and 5.0?g/kg. Adult mortality was assessed after 14?days of exposure. After this interval, the treated wheat was retained for an additional period of 90?days, in order to evaluate progeny production and wheat loss. At the concentrations of 0.5 and 1.0?g/kg, trans-cinnamaldehyde and eugenol achieved highest adult mortality. At 5.0?g/kg, all compounds except for p-cymene and α-pinene caused complete (100%) adult mortality. Generally, trans-cinnamaldehyde was the most potent compound causing complete inhibition of progeny at the three concentrations. Similarly, no progeny were observed in the wheat treated with (?)-citronellal, eugenol, p-cymene, (?)-menthone, and (?)-terpinen-4-ol at 5.0?g/kg after 45 and 90?days. Similar trends were noted for wheat weight loss and damage as the treatment with monoterpenes and phenylpropenes at the highest rate preserved the wheat intact and free from damage by S. oryzae for 90?days. Our findings suggest the tested compounds except p-cymene and α-pinene could be recommended for use as part of an integrated pest management program for S. oryzae control in stored wheat.     

Metabolism of monoterpenes: demonstration that (+)-cis-isopulegone, not piperitenone, is the key intermediate in the conversion of (-)-isopiperitenone to (+)-pulegone in peppermint (Mentha piperita)

Piperitenone is commonly considered to be the key intermediate in the conversion of (-)-isopiperitenone to (+)-pulegone in peppermint; however, [3H]piperitenone gave rise only to the inert metabolite (+)-piperitone when incubated with peppermint leaf discs. Under identical conditions, (-)-[3H]isopiperitenone was efficiently incorporated into (+)-pulegone, (-)-menthone, and (+)-isomenthone in leaf discs, and yielded an additional metabolite identified as (+)-cis-isopulegone; piperitenone was poorly labeled. Moreover, (+)-cis-[3H]isopulegone was rapidly converted to (+)-pulegone, (-)-menthone, and (+)-isomenthone in leaf discs, and the reduction of (+)-[3H]pulegone to (-)-menthone and (+)-isomenthone was similarly documented. Each step of the pathway was demonstrated in a crude soluble preparation from peppermint leaf epidermis and each of the relevant enzymes was partially purified in order to compare relative rates of catalysis. The results of these studies indicate that the endocyclic double bond of (-)-isopiperitenone is reduced to yield (+)-cis-isopulegone, which is isomerized to (+)-pulegone as the immediate precursor of (-)-menthone and (+)-isomenthone, and they rule out piperitenone as an intermediate of the pathway.     

Biocatalytic reduction of (+)-carvone and (−)-carvone in submerged cultures of the fungi Penicillium citrinum and Fusarium oxysporium

Abstract

Biocatalytic transformation represents a green approach to the asymmetric hydrogenation of activated alkenes. This paper details catabolic events after the addition of (?)-carvone or (+)-carvone to submerged cultures of Penicillium citrinum and Fusarium oxysporium. These microorganisms were shown to biotransform the isomers of carvone, leading to the formation of a diastereoisomeric excess of derivatives of carvone and reduced carveols, and also to isomerize both dihydrocarvone, and their derivatives dihydrocarveols.     

Insecticidal activities of monoterpenes and phenylpropenes against <Emphasis Type="Italic">Sitophilus oryzae</Emphasis> and their inhibitory effects on acetylcholinesterase and adenosine triphosphatases

In the present study, six monoterpenes [(?)-citronellal, p-cymene, (?)-menthone, α-pinene, α-terpinene, and (?)-terpinen-4-ol] and two phenylpropenes [trans-cinnamaldehyde and eugenol] were evaluated for their contact and fumigant toxicities against Sitophilus oryzae adults. The effects of these compounds on the mortality of S. oryzae adults in stored wheat and their inhibitory effects on acetylcholinesterase (AChE) and adenosine triphosphatases (ATPases) were examined. The tested compounds showed varying degrees of contact toxicity, with trans-cinnamaldehyde (LC₅₀ = 0.01 mg/cm²) being the most potent compound, followed by (?)-menthone (LC₅₀ = 0.013 mg/cm²) and eugenol (LC₅₀ = 0.015 mg/cm²). In a fumigant toxicity assay, the monoterpenes α-terpinene, p-cymene, and (?)-menthone showed the highest toxicities (LC₅₀ = 50.79, 52.37, and 54.08 μl/L air, respectively). Trans-cinnamaldehyde, (?)-citronellal, and eugenol were the least toxic (LC₅₀ > 100 μl/L air). In general, the oxygenated compounds exhibited high contact toxicities while the hydrocarbon compounds exhibited high fumigant toxicities. When tested for their insecticidal activities against S. oryzae in stored wheat, trans-cinnamaldehyde was found to be the most potent compound, with 73.9% mortality at an application rate of 0.5 g/kg and complete mortality (100%) at 1 and 5 g/kg after 1 week of treatment. All of the tested compounds showed AChE inhibition, although (?)-citronellal and trans-cinnamaldehyde presented the strongest enzyme inhibition, with IC₅₀ values of 18.40 and 18.93 mM, respectively. On the other hand, (?)-terpinene-4-ol exhibited the highest inhibition of ATPases, followed by α-pinene and α-terpinene.     

流行性出血热(EHF)病毒半微量甲基纤维素空斑法的建立

本文报道EHF病毒一种新的空斑形成按术,即半微量甲基纤维素空斑法的建立及其应用。6株来源不同的毒株均可在V_(ero)-E_6细胞或V_(ero)细胞上形成清晰的空斑,形成的空斑能被特异抗EHF病毒血清所中和。其敏感性与用琼脂糖作覆盖物的空斑法一致。该法具有操作简便、快速等优点,适用于EHF的病原学和血清学研究。     

Influence of the chirality of (R)-(-)- and (S)-(+)-carvone in the central nervous system: a comparative study

Many terpenes are used therapeutically, and as flavor and fragrance materials. (R)-(-)-Carvone, the main constituent of spearmint oil, and (S)-(+)-carvone, found as major component of caraway and dill seed oils, have several applications and are used in cosmetic, food, and pharmaceutical preparations. In this study, the effect of enantiomers of carvone on the central nervous system (CNS) was evaluated in mice. The LD50 value was 484.2 mg/kg (358.9-653.2) for (S)-(+)-carvone, and 426.6 (389.0-478.6) mg/kg for (R)-(-)-carvone. Both enantiomers caused depressant effects, such as decrease in the response to the touch and ambulation, increase in sedation, palpebral ptosis, and antinociceptive effects. (S)-(+)- and (R)-(-)-carvone caused a significant decrease in ambulation. (R)-(-)-Carvone appeared to be more effective than its corresponding enantiomer at 0.5 and 2.0 h after administration. However, (S)-(+)-carvone was slightly more potent at 1 h. In potentiating pentobarbital sleeping time, (R)-(-)-carvone was more effective than (S)-(+)-carvone at 100 mg/kg, but was less potent at 200 mg/kg compared to the (+)-enantiomer, indicating a sedative action. (S)-(+)-Carvone at the dose of 200 mg/kg increased significantly the latency of convulsions induced by PTZ and PIC, but (R)-(-)-carvone was not effective against these convulsions. These results suggest that (S)-(+)-carvone and (R)-(-)-carvone have depressant effect in the CNS. (S)-(+)-Carvone appears to have anticonvulsant-like activity.     

Specific anosmia to l-carvone: the minty primary odour

Specific anosmia to l-carvone has been found in about 8% ofthe human population. Olfactory thresholds of 24 chemicals exhibitinga minty odour have been measured with panels of normal and specificallyanosraic subjects. The results show that this anosmia is mostlyassociated with l-carvone and compounds very closely relatedboth in molecular shape and configuration. It is suggested thatl-carvone represents the best example of the "minty" primaryodour, already proposed by Amoore in 1962 and that the inabilityto smell it corresponds with the absence of a specific receptorprotein.     

The Structure of Graphinone

A microorganism M–2 was isolated as a strain capable of converting (—)-menthone to other compounds. The strain was identified as Pseudomonas fluorescens by taxonomical investigation. The conversion products of (—)-menthone were determined to be (—)-t-4-isopropyl-3-oxo-r-l-cyclohexanecarboxylic acid,* (+)-c-4-isopropyl-3-oxo-r-1-cyclohexane-carboxylic acid* and (+)-t-3-hydroxy-t-4-isopropyI-r-l-cyclohexanecarboxylic acid.* As the main pathway, it was proposed that (—)-menthone was oxidized to a keto acid which was successively reduced to a hydroxy acid.     

Activity and selectivity of some hydrolases in enantiomeric solvents

Summary The activity and the regio- and enantioselectivity of five lipases and one protease were investigated in the two enantiomeric solvents (R)-carvone and (S)-carvone. It was found that in all cases enzyme activity changed as a function of solvent configuration and that, for the same enzyme, it was higher in (R)-carvone or in (S)-carvone depending on the nature of the substrate. Instead, no significative variation of regio- and enantioselectivity was observed moving from one enantiomeric solvent to the other.