RICINOLEIC ACID LACTONE

Following developments of lactonization methodology, Shiina et al. proposed a novel mixed-anhydride method for the preparation of lactones including mediumsized ring compounds, and they applied this new technology to the preparation of several macrocyclic molecules (Scheme 5.8 and Scheme 5.9). This reaction could be promoted by Lewis acid catalysts, or nucleophilic catalysts, such as DMAP and DMAPO(4-dimethylaminopyridine N-oxide). For example, ricinoleic acid lactone (20) was first synthesized by combination of 4-trifluoromethylbenzoic anhydride (TFBA) with Lewis acid catalysts (Scheme 5.8) [34, 35], whereas aleuritic acid lactone (21) was alternatively synthesized using 2-methyl-6-nitrobenzoic anhydride (MNBA) with nucleophilic catalysts (Scheme 5.9) [36-38]. 

Decanolide (y-decalactone) Ricinoleic acid Yarrowia lipolytica llgL, 55 h, several tons per year Final acidification and temperature increase effect cyclisation of all 4-hydroxydecanoic acid to the corresponding lactone [222, 224, 228]... 

Finally, the yeast Yarrowia lipolytica is able to transform ricinoleic acid (12-hydroxy oleic acid) into y-decalactone, a desirable fruity and creamy aroma compound however, the biotransformation pathway involves fi-oxidation and requires the lactonisation at the CIO level. The first step of fi-oxidation in Y. lipolytica is catalysed by five acyl-CoA oxidases (Aox), some of which are long-chain-specific, whereas the short-chain-specific enzymes are also involved in the degradation of the lactone. Genetic constructions have been made to remove these lactone-degrading activities from the yeast strain [49, 50]. A strain displaying only Aox2p activity produced 10 times more lactone than the wild type in 48 h but still showed the same growth behaviour as the wild type. 

Decalactone Ricinolic acid, cor-rolic acid, Massoia lactone or 11-hydroxy hexadecanoic acid Candida species, Clador-sporium sua-volens, baker s yeast Peach, buttery... 

Traditional fermentation using microbial activity is commonly used for the production of nonvolatile flavor compounds such as acidulants, amino acids, and nucleotides. The formation of volatile flavor compounds via microbial fermentation on an industrial scale is still in its infancy. Although more than 100 aroma compounds may be generated microbially, only a few of them are produced on an industrial scale. The reason is probably due to the transformation efficiency, cost of the processes used, and our ignorance to their biosynthetic pathways. Nevertheless, the exploitation of microbial production of food flavors has proved to be successful in some cases. For example, the production of y-decalactone by microbial biosynthetic pathways lead to a price decrease from 20,000/kg to l,200/kg U.S. Generally, the production of lactone could be performed from a precursor of hydroxy fatty acids, followed by p-oxidation from yeast bioconversion (Benedetti et al., 2001). Most of the hydroxy fatty acids are found in very small amounts in natural sources, and the only inexpensive natural precursor is ricinoleic acid, the major fatty acid of castor oil. Due to the few natural sources of these fatty acid precursors, the most common processes have been developed from fatty acids by microbial biotransformation (Hou, 1995). Another way to obtain hydroxy fatty acid is from the action of LOX. However, there has been only limited research on using LOX to produce lactone (Gill and Valivety, 1997). 

Candida strains convert ricinoleic acid into If-decalactone, which displays the fatty, fruity aroma typical of peaches. Ricinoleic acid (12-hydroxy octadec-9-enoic acid) is the major fatty acid in castor oil (approx. 80 %). The yeast can lipolyze castor oil glycerides and the liberated ricinoleic acid is subsequently metabolized via d-oxidation and eventually converted to 4-hydroxy-decanoic acid (Figure 5). Recently a European patent has been filed (20) essentially covering the same procedure. Shake culture fermentations were carried out on 100 ml scale for one week. The 4-hydroxydecanoic acid formed was converted to )f-decalactone by boiling the crude, acidified (pH 1.5) fermentation broth for a period of 10 minutes. The lactone was isolated via solvent extraction and a yield of some 5 g/1 was obtained. The same lactone was detected as the major volatile component formed when the yeast, Sporobolomyces odorus was grown in standard culture medium (21). Although the culture medium displayed an intense fruity, typical peach-like odor, the concentration of y-decalactone amounted to no more than 0.5 mg/1. 

EtAlCh, a stronger Lewis acid than Me2AlCl, with a less nucleophilic alkyl group, successfully catalyzes the ene reactions of aliphatic aldehydes with terminal alkenes. Reaction of an aliphatic aldehyde with a terminal alkene and EtAlCh in CH2CI2 for a few minutes at 0 C gives the ene adduct as a 4 1 ( ) (Z) mixture in 50-60% yield. Reaction of 9-decenoic acid with 1 equiv. of acetaldehyde and 2.2 equiv. of EtAlCh affords (69) as a 4 1 ( ) (2) mixture in 66% yield. Lactonization of the ( )-isomer provides recifeiolide. Reaction of 10-undecenoic acid with 1 equiv. of heptanal and 2.2 equiv. of EtAlCh provides a 4 1 mixture of ricinelaidic acid ( )-(70) and ricinoleic acid (Z)-(70) in 41% yield (Scheme 14).27... 

Natural y-decalactone is produced biotechnologically starting from ricinoleic acid, which is degraded by P-oxidation to 4-hydroxydecanoic acid, which lactonizes at lower pH to yield y-decalactone [197a], [197b],... 

Ricinelaidie acid lactone. Details are available for isomerization of ricinoleic acid (1) to ricinelaidie acid (2) and for lactonization of the latter acid promoted by silver perchlorate or silver trifluoiometbanesulfonate. ... 

One of the earliest and most commercially successful examples of producing flavoring materials by fermentation is the production of 4-decalactone from castor oil (Figure 9.11, [83]). Castor oil is unique in that it is made up of nearly 80% ricinoleic acid (12-hydroxy-9-octadecenoic acid). Yarrowia lipolytica initially hydrolyses the ricinoleic acid from the triglyceride and then through P-oxidation, converts this acid to 4-hydroxydecanoic acid. This acid forms a lactone at low pHs to yield the y-decalactone. The yield on this process is generally considered to be ca. 6 g/L which is very attractive. 

Hydroxycarboxylic acids and 5-hydroxycarboxylic acids occur in the form of corresponding y- and 5-lactones in many fruits, especially apricots and peaches. Many other hydroxy fatty acids are also found in seed oils of plants. For example, (S)-jalapinolic acid (3-28) occurs in lipophilic ester-type dimers of acylated pentasaccharides derived from L-rhamnose in sweet potato Ipomoea batatas, Convolvulaceae), which are known as batatins. (9Z,12S)-12-Hydroxyoctadec-9-enoic (ricinoleic) acid (3-29) occurs in castor oil, where it represents about 90% of the total fatty acids. So-called castor oil is extracted from the seeds of the castor oil plant Ricinus communis) of the Euphorbiaceae family, and is used only for technical purposes as it has purgative properties. 

These reactions may be performed within one cell or in several distinct process steps. The first important step in the conversion of fatty acids to lactones is synthesis of hydroxy fatty acids. The availability of a certain lactone is limited by the availability of the corresponding hydroxy fatty acids. A prominent source is castor oil, which contains a large amount of ricinoleic acid (Biermaim et al. 2011). The hydroxy group is inserted by a non-heme hydroxylase, which is closely related to an oleate-12-desaturase (Broun et al. 1998). 

The synthesis of y-DL is the most prominent example for the microbial production of fragrance lactones. Nevertheless, the biotransformation route via P-oxidation and lactonization (Fig. 1) in yeast can be applied for the production of several lactones provided that a suitable hydroxy fatty acid as starting material is available. For example, ricinoleic acid, the starting compound for the production of y-DL, can be isolated in large quantities from castor oil. However, other hydroxy fatty acids are more difficult to obtain. For instance, researchers from Takasago International Corporation reported the conversion of 11-hydroxy palmitic acid ethyl ester to 8-decalactone by the yeast Candida sorbophila (Mitsuhashi and limori 2004). 0.13 g substrate in 30 itiL culture medium yielded 0.019 g 8-decalactone in 96 % ee optical purity after 11 days. 

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