Biotransformation of Citrus Aromatics Nootkatone and Valencene by Microorganisms

Abstract

We are continuing to study the biotransformation of secondary metabolites such as terpenoids and aromatic compounds from crude drugs and liverworts by microorganisms [1][2][3][4][5][6][7] and mammals 8,9) to obtain some functional substances such as pheromones and aromatics. We reported the biotransformation of sesquiterpenoids such as dehydrocostuslactone, costunolide, a-, b-, and g-cyclocostunolides, asantonin, and atractylon from crude drugs, and an amber constituent, (Ϫ)-ambrox by microorganisms such as Aspergillus niger.10) It has been clarified that a grapefruit essential oil containing nootkatone (1) decreases the somatic fat ratio 11) and its demand by cosmetic and fiber manufacturers has increased. Recently, we have found that the commercially available and cheap aromatic valencene (2) from Valencia orange oil is very efficiently converted into the expensive grapefruit aromatic, nootkatone (1) by biotransformations using Chlorella sp.12) and Mucor sp. 13) In continuation of the biotransformation of the chemical constituents isolated from crude drugs into biologically active compounds, the biotransformations of nootkatone (1) and valencene (2) were examined using Aspergillus niger, Fusarium culmorum, and Botryosphaeria dothidea. This paper deals with the structural elucidation of metabolites of 1 and 2 converted by the three fungi.Biotransformation of Nootkatone (1) by Aspergillus niger A. niger was inoculated and cultivated in a rotary (100 rpm) in Czapek-pepton medium (pH 7.0) at 30°C for 7 d. (ϩ)-Nootkatone (1) (80 mg/200 ml) was added to the medium and further cultivated for 7 d. The crude metabolites obtained from the culture broth by EtOAc extraction were chromatographed on silica gel (n-hexane-EtOAc gradient) to give two metabolites, 12-hydroxy-11,12-dihydronootkatone (3) (10.6%, isolated yield) and C-11 stereomixtures of 11,12-dihydroxy-11,12-dihydronootkatone (nootkatone-11,12-diol) (4, 5) (51.5% isolated yield), respectively.Compound ( Compound 3 showed correlations between (i) H-12/C-7, C-11, and C-13; and (ii) H-13/C-7, C-11 and C-12 in the HMBC spectrum. On the basis of the above spectral data and careful analysis of its 2D NMR spectrum, the structure of metabolite 3 was established to be 12-hydroxy-11,12-dihydronootkatone. The relative configuration at C-11 remained to be clarified.The HR-EI-MS of nootkatone-11,12-diol (a mixture of 4 and 5) showed a peak for [M ϩ ] at m/z 252.1730, indicating the molecular formula of C 15 H 24 O 3 . The FT-IR spectrum of the mixture indicated the presence of a hydroxyl (3358 cm Ϫ1 ) and a conjugated ketone (1652 cm Ϫ1 ) group. The 1 H-and 13 C-NMR spectra showed that 4 and 5 were a mixture of stereoisomers at C-11, the isolation of which was very difficult by any separation method. The structure of 11,12-diol was confirmed by the formation of a methyl ketone (6) on oxidation with NaIO 4 . Treatment of the mixture (4, 5) with 1,1Ј-thiocarbonyldiimidazole gave the thiocarbonates 7 and 8, which were easily separated by HPLC in the ratio of 3 : 2. Teresa ...

Eremophilane-type sesquiterpenes from Alpinia oxyphylla with inhibitory activity against nitric oxide production

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, along with eleven known compounds (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Among them, compounds 2-6, 9, and 11 were isolated from this genus for the first time.

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“…Furthermore, we recently reported a series of new sesquiterpenes, including seven new eudesmane sesquiterpenes, against NO production from A. oxyphylla [6][7][8]. In continuation of our search for bioactive metabolites from the fruits of A. oxyphylla, we have further isolated 12 eremophilane-type sesquiterpenes, including a new compound, (4R*,5R*)-7-acetyl-4,5-dimethyl-4,5,8,9-tetrahydronaphthalen-2(3H)-one (oxyphyllanone A, 1), along with eleven known sesquiterpenes, (4R*,5S*,7R*)-7-acetyl-4,5-dimethyl-4,5,6,7,8,9-hexahydronaphthalen-2(3H)-one (2) [9], (11R)-nootkatone-11,12-diol (3) [9], (11S)-nootkatone-11,12-diol (4) [9], 11-hydroxyvalenc-1(10)-en-2-one (5) [10], 9E-hydroxynootkatone (6) [9], oxyphyllol B (7) [2], oxyphyllol C (8) [2], epinootkatol (9) [11, 12], nootkatol (10) [12,13], 12-hydroxynootkatone (11) [9,14], and nootkatone (12) [11]. Among them, compounds 2-6, 9, and 11 were isolated from this genus for the first time.…”

Chemotaxonomic value of essential oil components in liverwort species. A review

“…[11] All mentioned chemotypes have been described on the basis of chemical data obtained from solvent extracts. [18,[45][46][47] There is only one scientific paper concerning the chemical composition of EOs hydrodistilled from this liverwort species. Warmers and König [48] showed that gymnomitranes and cuparanes are the major components present in EOs obtained from the European specimen, as well as in the solvent extract.…”

Natural Sesquiterpenoids

“…The biotransformation of the latter by the fungus Aspergillus niger has also been described in this work. 124 A gas chromatographic method has been developed to quantify the chamigrane sesquiterpene elatol, at the surface and within the thallus, of 70 specimens of the red alga Laurencia obtusa. 125 This species also contains the new sesquiterpenes perforenol B 145 and the perforetane derivative 146.…”