Valencene oxidation

The main products of limonene oxidation, carvone and carveol, cause a terpenic off-flavour in essential oils and juices. Valencene oxidation products, such as (-F)-nootkatone, cause a grapefruit-like off-flavour in orange juices. Large amounts of alcohol (-F)-o(-terpineol, which arises, for example, during storing of juices by acid catalysed hydration or microbial transformation of limonene, is also perceived as an off-flavour. 

Wilson, C. W. et al., J. Agric. Food Chem., 1978, 26, 1430-1432 Oxidation of the sesquiterpene valencene to the 4-en-3-one proceeds explosively when at sub-ambient temperatures [1], A safer alternative oxidation procedure is detailed [2],... 

The allylic oxidation of the sesquiterpenoid (+)-valencene has been performed using f-BuOOH as the oxidant and BiCl3 as catalyst. Nootkatone was the major product, isolated in 35% yield by flash chromatography (ethyl acetate - light petroleum, boiling point 40-60 °C) (Scheme 17) [87, 88]. 

Scheme 17 BiCl3-catalyzed allylic oxidation of (+)-valencene using /-BuOOH...

Nootkatone can be prepared by oxidation of valencene, a sesquiterpene hydrocarbon isolated from orange oils. 

Nootkatone is an important constituent from grapefruit flavour. It is synthesised by oxidation of valencene, which is obtained and isolated from orange peel oil where it occurs at a maximum level of 0.4% [9]. 

For the oxidation of valencene to nootkatone, strong oxidation agents like oxygen in the presence of metal salts, peroxides or chromate compounds are required. There are also several patents on the bioconversion of valencene to nootkatone which results in natural nootkatone (Scheme 13.9) [10,11]. 

Very recently, the chemoenzymatic preparation of nootkatone from valencene was described [150]. Nootkatone was prepared from valencene by copper(I) iodide catalysed oxidation with tert-butyl hydroperoxide and hydroxylated at C-9 by Mucor plumbeus and Cephalosporium aphidicola. 

The most important (and also the most expensive) grapefruit aroma compound is the bicyclic terpene nootkatone. It is manufactured by oxidation of valencene, which is extracted from Valencia oranges. Figure 1.23 shows two routes for this oxidation, a stoichiometric reaction using chromium trioxide, and a catalytic alternative using sodium hypochlorite (bleach) in the presence of 1 mol% osmium tetraoxide catalyst. 

The main essential oil components of the edible fruits of G. huillensis Welw. ex. Oliv. growing wild in the Gutu and Rusape areas of Zimbabwe are a-humulene (23.0%), valencene (18.2%), caryophyllene (12.6%), caryophyllene oxide (6.3%) and 8-selinene (5.0%) (Chagonda Lameck and Chalchat, 2005). 

The identification of dihydro-a -agarofuran (191) as a microbial oxidation product of valencene (190) has resulted in a revised configuration for dihydro-j3-agarofuran... 

For the synthesis of flavour-active compounds numerous methodologies have been developed [17], In many cases natural products served as starting materials such as eugenol from clove oil for the synthesis of vanillin. In case of complex stereochemistry natural materials are still welcome for the synthesis of valuable flavour compounds such as nootkatone, which is obtained by oxidation from valencene. 

Experiments were performed in which the catalyst (CrAPO-5, CrAPO-11 and CrS-1) was filtered, at the reaction temperature (80 °C), after 30 minutes, which corresponded to 30-40% conversion. Filtration at the reaction temperature is important in order to avoid possible readsorption of leached metal ion on cooling. When the filtrate was allowed to react further at 80 "C the reaction contmued at roughly the same rate. Further insights into the mechanism of catalysis were obtained fiom the allylic oxidation of valencene (I) which is too bulky to enter... 

Cankar K, van Houwelingen A, Bosch D, Sonke T, Bouwmeester H, Beekwilder J (2011) A chicory cytochrome P450 monooxygenase CYP71AV8 for the oxidation of (+)-valencene. FEBS Lett 585 178-182... 

The expensive grapefruit aromatic nootkatone (2) used by cosmetic and ber manufacturers was obtained in high yield by biotransformation of (+)-valencene (1), which can be cheaply obtained from Valencia orange, by Chlorella species, fungi such as Mucor species, B. dothidea, and B. theobromae. This is a very inexpensive and clean oxidation reaction, which does not use any heavy metals, and thus, this method is expected to nd applications in the industrial production of nootkatone. 

Successful attempts to engineer mutants for selective oxidation of cheap terpenes to expensive oxidized derivatives have also been accomplished. Rational mutants of P450cam exhibited activity toward the sesquiterpene (+ )-valencene (48) and produced > 85% of (-F )-frans-nootkatol and (+ )-nootkatone [201]. The monoterpene (+ )-a-pinene (49) was oxidized by P450cam mutants to 86% (+ )-as-verbenol or to a mixture of (+ )-verbenone and (+ )-cis-verbenol (Figure 12.3) [202]. Verbenol and verbenone are active pheromones against various beede species. 

The same group also reported the selective allylic oxidation of unsaturated steroids and valencene by a series of metal complexes based on Co(II), Cu(II), Mn(II) and V(II) immobilized on mesoporous silica using a synthetic strategy similar to that reported in Scheme 23.71. The catalysts could be recycled with only minor loss of activity. 

Metal-catalyzed oxidation or photooxidation of valencene to nootkatone... 

Monocyclic sesquiterpenic ketone (-f)-flr-turmerone (8-52) is the main component (25-50%) of turmeric essential oil (see Table 8.32). It is formed by oxidation of hydrocarbon (-l-)-flr-curcumene, which is present in turmeric rhizomes at a level of about 6%. Bicyclic sesquiterpenic ketone is (-l-)-nootkatone (8-52), which is an important odorous compound of grapefruits formed by oxidation of hydrocarbon (-l-)-valencene via alcohol (-l-)-P-nootkatol. Another oxidation product of valencene is... 

Nootkatone is prepared by oxidation of either valencene (297) or nootkatene (298), as shown in Fig. 8.56. Its usage is restricted largely by its intensity rather than its price although the latter is in thousands of dollars. Valencene has been isolated from orange... 

The extraction of natural nootkatone from citrus oil and peel is too expensive, because the process is characterized by low yields and high biomass production, and it suffers from annual harvest fluctuations. The chemical oxidation of the sesquiterpene valencene extracted from orange peels often results in off-notes, and it has the disadvantage of employing heavy-metal salts as strong oxidants thus the final product cannot be labeled as natural. Therefore, biotechnological routes have been extensively studied in the last decade to find an economical and sustainable synthetic procedure to natural nootkatone. Most of them make use... 

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