Modification of valencene by bio- and chemical transformation.

Highly efficient production is discussed of nootkatone, the most important fragrant component of grapefruit and which possesses anti-obesity activity, from valencene, obtained from Valencia orange, by the green alga, Chlorella, and the fungi, Mucor, Botryospaeria and Botryodiplodia. The microorganisms introduce an oxygen atom at an allylic position to give secondary hydroxyl and keto groups. The presented methods are a cheap one step reaction, non-hazardous and very useful for the production of fragrant components from commercially available natural sesquiterpene hydrocarbons.

Biotransformation of (-)-(R)-α-phellandrene: antimicrobial activity of its major metabolite.

Terpene derivatives converted by microbial biotransformation constitute an important resource for natural pharmaceutical, fragrance, and aroma substances. In the present study, the monoterpene α-phellandrene was biotransformed by 16 different strains of microorganisms (bacteria, fungi, and yeasts). The transformation metabolites were initially screened by TLC and GC/MS, and then further characterized by NMR spectroscopic techniques. Among the six metabolites characterized, 6-hydroxypiperitone, α-phellandrene epoxide, cis-p-menth-2-en-1-ol, and carvotanacetone, which originated from (-)-(R)-α-phellandrene, are reported for the first time in this study. Additionally, the substrate and the metabolite 5-p-menthene-1,2-diol were subjected to in vitro antibacterial and anticandidal tests. The metabolite showed moderate-to-good inhibitory activities (MICs=0.125 to >4 mg/ml) against various bacteria and especially against Candida species in comparison with its substrate (-)-(R)-α-phellandrene and standard antimicrobial agents.

Microbial transformation of (-)-nopol benzyl ether: direct dihydroxylation of benzene ring.

The biotransformation of (-)-nopol benzyl ether (5) by Aspergillus niger TBUYN-2 and A. niger Tiegh CBSYN was investigated. A. niger biotransformed 5 to afford (-)-4-oxonopol-2',4'-dihydroxybenzyl ether (6), and (-)-4-oxonopol (7) as main products. Compound 6 showed strong antioxidant activity (IC50 30.2 microM), which was very similar to that of butyl hydroxyl anisol (BHA).

Biotransformation of sesquiterpenoids from liverworts by fungi and mammals.

Biotransformation of sesquiterpenoids isolated from several liverworts using various fungi and mammals is summarized. Microorganisms introduce an oxygen atom at an allylic position to give secondary hydroxyl and keto groups. The cyclopentane ring is also oxidized to afford monoketo, and mono- and diols. Double bonds are also either reduced or oxidized to give either saturated compounds or epoxides, followed by hydrolysis to afford diols. The methyl group is oxidized to give a primary alcohol. Some fungi cleave the cyclopropane ring to form a 1,1-dimethyl group. These reactions precede stereo- and regiospecifically. Cytochrome P-450 is responsible for the introduction of an oxygen function into the substrates. The present methods are cheap, one step reactions, non-hazardous, and very useful for the production of some bioactive compounds from a large number of terpenoids found in liverworts and higher plants.

Biotransformation of alpha-cedrol and caryophyllene oxide by the fungus Neurospora crassa.

Incubation of alpha-cedrol and caryophyllene oxide with Neurospora crassa afforded 12beta-hydroxy cedrol, 10alpha-hydroxy cedrol, and 3beta-hydroxy cedrol, and 12beta-hydroxy caryophyllene oxide as major metabolites, respectively. The antibacterial and radical scavenging activities of the metabolites were evaluated in vitro using broth microdilution and bioauthographic techniques. However, no significant antibacterial and antioxidant activities were observed when compared with those of standard substances.

Isolation and structures of new cyclomyltaylane and ent-chamigrane-type sesquiterpenoids from the liverwort Reboulia hemishaerica and their biotransformation by the fungus Aspergillus niger.

Reboulia hemisphaerica, the thalloid liverwort, contained four new cyclomyltaylane- and two new ent-beta-chamigrane-type sesquiterpenoids of which the absolute stereostructures were established by a combination of two-dimensional NMR spectroscopy, X-ray crystallographic analysis, and the modified Mosher's method. Cyclomyltaylan-5alpha-ol and ent-beta-chamigren-1alpha-ol were biotransformed by the fungus Aspergillus niger to afford new oxygenated matabolites. Their structures were also elucidated in the same manner as described above.

Biotransformation of aristolane- and 2,3-secoaromadendrane-type sesquiterpenoids having a 1,1-dimethylcyclopropane ring by Chlorella fusca var. vacuolata, mucor species, and Aspergillus niger.

Biotransformation of the aristolane-type sesquiterpene hydrocarbon (+)-1(10)-aristolene (1) from the crude drug Nardostachys chinensis and of the 2,3-secoaromadendrane-type sesquiterpene lactone plagiochilide (2) from the liverwort Plagiochila fruticosa by three microorganisms, Chlorella fusca var. vacuolata, Mucor species, and Aspergillus niger was investigated. C. fusca var. vacuolata and Mucor sp. introduced oxygen function into the cyclohexane ring of aristolene while A. niger oxidized stereoselectively one methyl of the 1,1-dimethyl group on the cyclopropane ring of aristolanes and 2,3-secoaromadendrane to give C-12 primary alcohol and C-12 carboxylic acid. The possible metabolic pathway of the formation of new metabolites is discussed. The stereostructures of new metabolites were established by a combination of NMR spectroscopy including HMBC and NOESY, X-ray crystallographic analysis, and chemical reaction.

The essential oil constituents and antimicrobial activity of Anthemis aciphylla BOISS. var. discoidea BOISS.

The essential oil of aerial parts, leaves and flowers of the endemic Anthemis aciphylla BOISS. var. discoidea BOISS. (Asteraceae) were obtained by hydrodistillation. The oils were analyzed both by GC and GC-MS on a polar column. The monoterpenes alpha-pinene (9-49%) and terpinen-4-ol (22-32%) were characterized as the main constituents. An unknown component isolated from the essential oil was characterized by means of MS, HR-MS, FT-IR, 1D- and 2D-NMR techniques as isofaurinone (1). Furthermore, the biological activity of the essential oils was evaluated in various human pathogenic microorganisms using the broth microdilution method. Weak to moderate inhibitions (0.06-1.0 mg/ml) was observed.

Biotransformation of citrus aromatics nootkatone and valencene by microorganisms.

Biotransformations of the sesquiterpene ketone nootkatone from the crude drug Alpiniae Fructus and grapefruit oil, and the sesquiterpene hydrocarbon valencene from Valencia orange oil were carried out with microorganisms such as Aspergillus niger, Botryosphaeria dothidea, and Fusarium culmorum to afford structurally interesting metabolites. Their stereostructures were established by a combination of high-resolution NMR spectral and X-ray crystallographic analysis and chemical reaction. Metabolic pathways of compounds and by A. niger are proposed.

Highly efficient production of nootkatone, the grapefruit aroma from valencene, by biotransformation.

Nootkatone, the most important and expensive aromatic of grapefruit, decreases the somatic fat ratio, and thus its demand is increasing in the cosmetic and fiber sectors. A sesquiterpene hydrocarbon, (+)-valencene, which is cheaply obtained from Valencia orange, was biotransformed by the green algae Chlorella species and fungi such as Mucor species, Botryosphaeria dothidea, and Botryodiplodia theobromae to afford nootkatone in high yield.

Penicillium sclerotiorum catalyzes the conversion of herbertenediol into its dimers: mastigophorenes A and B.

Herbertenediol was subjected to biotransformation by Penicillium sclerotiorum. Spectral data analysis of the converted metabolites revealed that the neurotrophic active compounds, mastigophorenes A and B, dimeric to the substrate were formed.

Microbial transformation of (-)-carvone.

The cyclic monoterpene ketone (-)-carvone was metabolized by the plant pathogenic fungus Absidia glauca. After 4 days of incubation, the diol 10-hydroxy-(+)-neodihydrocarveol was formed. The absolute configuration and structure of the crystalline substance was identified by means of X-ray diffraction and by spectroscopic techniques (MS, IR and NMR). The antimicrobial activity of the substrate and metabolite was assayed with human pathogenic microorganisms.

Ferulagone: a new monoterpene ester from Ferulago thirkeana essential oil.

Essential oil obtained by micro-distillation and hydrodistillation of the endemic Ferulago thirkeana (Boiss.) Boiss. (Apiaceae) was analysed by GC/MS. An unknown component isolated from the essential oil was characterized by chromato-spectral techniques (1D-, 2D-NMR, HRMS, IR and UV) as (1 S)-2,6,6-trimethyl-4-oxobicyclo[3.1.1]hept-2-enyl(2 E)-2-methylbut-2-enoate (= ferulagone or 1-angeloyloxyverbenone) (1). Biological activities of the essential oil and the purified major component (1) were tested against various human pathogenic microorganisms resulting in moderate inhibition (62.5 - 125 microg/ml).