Limonene-1,2-diol

Very recently, the purification and characterisation of an epoxide hydrolase, catalysing the conversion of limonene-1,2-epoxide to limonene-1,2-diol has been described [90]. The enzyme was isolated from Rhodococcus erythropolis DCL14 and is induced when the microorganism is grown on monoterpenes. The authors found evidence that the enzyme, limonene-1,2-epoxide hydrolase is the first member of a new class (the third class) of epoxide hydrolases [91]. 

LEH originates from the bacterium Rhodococcus erythropolis DCL14." ° LEH is part of a limonene degradation pathway where it catalyzes the conversion of limonene-1,2-epoxide to limonene-1,2-diol (Scheme... 

Figure 3 Conversion of 5 (helicity 3,4 P) in the LEH active site model. Two possible reaction pathways are shown. Only the product (1S,2S,4f )-limonene-1,2-diol is observed experimentally. Insets show the substrate conformation. Asterisks indicate atoms, which in calculations were fixed to their crystallographically observed position.

Another illustration of the use of such a biocatalytic approach was the synthesis of either enantiomer of a-bisabolol, one of these stereoisomers (out of four) which is of industrial value for the cosmetic industry. This approach was based on the diastereoselective hydrolysis of a mixture of oxirane-diastereoiso-mers obtained from (R)- or (S)-limonene [68]. Thus,starting from (S)-hmonene, the biohydrolysis of the mixture of (4S,81 S)-epoxides led to unreacted (4S,8S)-epoxide and (4S,8i )-diol. The former showed a diastereomeric purity (> 95%) and was chemically transformed into (4S,8S)-a-bisabolol. The formed diol... 

Limonene (92) is the most widely distributed terpene in nature after a-pinene [68]. The (+)-isomer is present in Citrus peel oils at a concentration of over 90% a low concentration of the (-)-isomer is found in oils from the Mentha species and conifers [26]. The first data on the microbial transformation of limonene date back to the sixties. A soil Pseudomonad was isolated by enrichment culture technique on limonene as the sole source of carbon [69]. This Pseudomonad was also capable of growing on a-pinene, / -pinene, 1-p-menthene and p-cymene. The optimal level of limonene for growth was 0.3-0.6% (v/v) although no toxicity was observed at 2% levels. Fermentation of limonene by this bacterium in a mineral-salts medium resulted in the formation of a large number of neutral and acidic products. Dihydrocarvone, carvone, carveol, 8-p-menthene-1,2-cw-diol, 8-p-menthen-1 -ol-2-one, 8-p-menthene-1,2-trans-diol and 1 -p-menthene-6,9-diol were among the neutral products isolated and identified. The acidic compounds isolated and identified were perillic acid, /Msopropenyl pimelic acid, 2-hydroxy-8-p-menthen-7-oic acid and... 

As mentioned before, a Pseudomonas incognita was isolated by enrichment technique on the monoterpene alcohol linalool that was also able to grow on geraniol, nerol and limonene [36]. The metabolism of limonene by this bacterium was also investigated [37]. After fermentation the medium yielded as main product a crystallic acid, perillic acid, together with unmetabolised limonene, and some oxygenated compounds dihydrocarvone, carvone, carveol, p-menth-8-en-1 -ol-2-one, p-menth-8-ene-1,2-diol or p-menth-1 -ene-6,9-diol (structure not fully elucidated) and finally / -isopropenyl pimelic acid. 

The fungal bioconversion of limonene was further studied [82]. Penicillium sp. cultures were isolated from rotting orange rind that utilised limonene and converted it rapidly to a-terpineol. Bowen [83] isolated two common citrus moulds, Penicillium italicum and P. digitatum, responsible for the postharvest diseases of citrus fruits. Fermentation of P. italicum on limonene yielded cis- and frans-carveol (93) (26%) as main products, together with cis- and from-p-mentha-2,8-dien-l-ol (110) (18%), (+)-carvone (94) (6%), p-mentha-1,8-dien-4-ol (111) (4%), perillyl alcohol (100) (3%), p-menth-8-ene-1,2-diol (98) (3%), Fig. (17). Conversion by P. digitatum yielded the same products in lower yields. The two alcohols />-mentha-2,8-dien-1 -ol (110) and p-mentha-1,8-dien-4-ol (111) were not described in the transformation studies where soil Pseudomonads were used [69]. 

Cyclic hydroboration of ( + )-limonene with thexylborane yields the pure borabicyclic compound (138), which is oxidized to the diol (32 X = OH) or protonol-ysed with acetic acid to yield pure (—)-carvomenthol (32 X = H) after the usual oxidation.227 The treatment of dialkylcyanothexylborates with trifluoroacetic anhydride followed by oxidation as a route to ketones has been used with ( + )-limonene to give the two bridged-ring ketones (139).228... 

A low purity (40-80%) divinylbenzene and chloromethylstyrene were used in the presence of a Friedel-Crafts catalyst (AICI3) for the synthesis of a polymeric phenolic antioxidant from p-cresol and l,3-bis(l-hydroxy-l-methylethyl)benzene in the presence of p-toluene sulfonic acid [115]. The obtained product was either used directly as AO for thermosetting resins or was treated consecutively with a-methylstyrene [116] or /ert-butylalcohol [117]. Other polymeric phenolic AO were obtained by reaction of phenol with p-men thane-1,8-diol, l-p-menthen-8-ol or limonene [118] or of p-cresol with 3- or 4-chloromethylstyrene in the presence of BF3-etherate or anhydrous AICI3 [119] the product thus obtained was finally aralkylated by a-methylstyrene. Thermostabilizer and/or LS for PUR was obtained, e.g. 98. 

Photoreaction on (-i-) limonene (orange oil) produces mixed isomers, first couple of fractions canbe used to create active CBl agonists see Schenck 1964. cfs-p-Menth-2-ene-l,8,-diol and mixed isomers from a culture of Penicillium italicum andP digitatum (moldy oranges) see Bowen (1975). 

Comparative studies with acetaminophen indicate that metabolism in the hamster resembles more closely that in man than in mouse. d-Limonene (32) is metabolized in rat, rabbit and hamster preferentially to C-l carboxylic acid derivatives, whereas dog and man largely form the 8,9-diol, and the guinea pig metabolizes 32 by these two pathways to the same extent . Compound 41 is substantially oxidized by rat and guinea pig, but not man, to biphenylacetic acid this possibly explains the ineffectiveness of 41 in rheumatoid arthritis . Sedative-hypnotic 42 is N-hydroxvIated in the cat, a more... 

Figure 2. Structures of terpenoids chemically formed from linalool (1 ) at pH 3.5 (cf. Fig.1-4). (2) 2,4(8)-p-menthadiene (3) B-myrcene (4) a-phellandrene (5) cx-terpinene (6) limonene (7) B-phellandrene (8) (Z)-ocimene (9) y-terpinene (10) (E)-ocimene (11) p-cymene (12) terpinolene (13) (E,Z)-alloocimene (14) (E,E)-alloocimene (15) a-terpineol (16) 3,7-dimethyl-l-oct-ene-3,7-diol (17) 1,8-cineole (18) 2,2,6-trimethyl-2-vinyl-te-trahydropyran.

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