Unsaturated anacardic acids

Subsequently, this approach to the synthesis of C15 phenolic lipids consisted in the route ArCi - ArCis. It has proved generally convenient for the synthesis of the unsaturated anacardic acids. From the methodological view it is also an aspect of the use of acyclic intermediates discussed in the next section since the starting material ethyl 2-methoxy-6-methylbenzoate is prepared from ethyl acetoacetate. 

A chemical/chromatographic method has been used to determine the first double bond position in the unsaturated anacardic acid constituents of Pistacia vera (ref. 9). The isolated constituent was methylated, dihydroxylated with performic acid, hydrolysed to remove some formate ester, oxidised with potassium periodate in acidic solution and the aldehydes formed reduced with sodium borohydride to the primary alcohols (refs. 226). The retention time of the aromatic product methyl 2-methoxy-6-(8-hydroxyoctyl)benzoate (C8 side chain) was compared with those of the Cl, C3, C7 and CIO synthetic analogues and from the linear plot of retention time against methylenic carbon chain length, the double bond could be readily assigned to the 8-position. Nevertheless mostly on account of limited sample availability and the time involved in purely synthetic verification. 

Dimethyl Disulfide Derivatization. Dimethyl disulfide (DMDS) derivatization was performed on the unsaturated anacardic acids in order to locate the position of the double bond (2.). A solution of the anacardic acid (0.05-0.1 mg) was dissolved in hexane (1.75mL). DMDS (2.5mL) and iodine solution (0.25mL of a 60mg la/mL ether) were added to the reaction vial, and the reaction was allowed to run overnight at 40°C. After the reaction was complete, 5mL of a 5% (w/v) solution of sodium thiosulfate was added to the reaction mixture to remove the excess iodine. The organic layer was removed, and evaporated to leave the crude DMDS derivative, which was purified by hpic, before being submitted for mass spectrometric analysis. 

HPLC Analysis. HpIc analysis of the resistant exudate (Figure 1) showed that there are two major compounds which are known to be the C22 co5 (compound B) and C24 o>5 (compound I) unsaturated anacardic acids from earlier work, and a number of minor compounds of which only the C22 saturated (compound G) and C24 saturated (compound M) anacardic acids have previously been identified f2-61. Of the uncharacterized compounds, E and J are of particular interest, as they are present in similar quantities to the C22 and C24 saturated anacardic acids. This analysis is in good agreement with the capillary gc method used by Walters, who identified the four major anacardic acids and found them in similar quantities to those seen in the hpic trace. 

Compound D. The mass spectrum of D gave a molecular ion of m/z 400, and the expected ion at m/z 368 from the loss of CH3OH. Compound D was therefore identified as a C24 unsaturated anacardic acid, but containing two double bonds. 

This ambiguity was easily solved by the nmr spectrum, which showed that the terminal methyl signal (50.86ppm) was a simple 3 proton triplet, which hence proved that the double bond was located at the co6 position. In addition coupling constants of 5.2 and 5.0Hz indicated that the the double bond was cis. Hence E is identified as the cis 23(06 unsaturated anacardic acid. 

Compound H. The mass spectrum shown in Figure 5 has a molecular ion at m/z 402 and the usual ions at m/z 180, 161, 148 and 121 indicating that H is a C24 unsaturated anacardic acid. The ion at m/z 370 is formed from the loss of CH3OH from the molecular ion. The DMDS derivative gave the spectrum shown in Figure 6. The expected molecular ion at m/z 496 was seen and the fragment at m/z 173 located the position of unsaturation as... 

From Table IV, resistant exudate is predominantly unsaturated, with the C22 o)5 and C24 (o5 anacardic acids making up 80% of the total exudate. In addition there is a small amount of C26 (a5 anacardic acid, which brings the total amount of a>5 unsaturated anacardic acids to 82%. There interestingly is also a significant quantity of the C23 o>6 anacardic acid and a small amount of the C25 co6 anacardic acid, which together contribute nearly 4% to the exudate composition. The remainder of the exudate is composed of saturated anacardic acids, the major compounds being the C22 and C24 saturated and C23 anteiso saturated anacardic acids. 

The identification of o)6 unsaturated compounds is interesting because all previous studies on the biosynthesis of anacardic acids pointed to an (o5 desaturase, forming Cie and Cis 0)5 unsaturated fatty acids which would then be processed into the C22 and C24 o)5 unsaturated anacardic acids (5. 10. 11.T The studies also suggest there is a mechanism whereby the a>5 fatty acids, which are only present in small amounts (<1%) in comparison with the total fatty acid pool, are specifically selected in preference to all the other fatty acids, and synthesized into (o5 anacardic acids. Hence the finding of o>6 unsaturated anacardic acids in significant amounts may suggest that there is some flexibility in the selection mechanism. 

The susceptible exudate, by contrast is predominantly saturated, but unsaturated anacardic acids, different from those observed in the resistant plants, still compose about 30% of the exudate. Of the saturated compounds, the C22 and C24 saturated anacardic acids are the major components, making up about 50% of the exudate. The remaining 20% is a complex mixture of odd chain length and branched chain anacardic acids, of which the C23 anteiso and the C23 straight chain saturated anacardic acids make up the majority, although the C24 iso and C25 anteiso compounds are also present in significant amounts. 

Of the remaining 30% of the exudate which is unsaturated, the most striking thing to note is the almost complete lack of any 5 is not seen at all. The unsaturated exudate is instead composed of two compounds, the C24 o)6,9 and the C24 (o9 anacardic acids, the former contributing nearly 17% to the total exudate composition, and the latter nearly 8%. From the biosynthetic scheme proposed in earlier work, it is more than likely that these two compounds are derived from the C18 6,9 and 9 unsaturated fatty acids, linoleic and oleic acids f5. 10. 111. The C24 6,9 anacardic acid is also present in the resistant exudate, but only contributes around 1% of the total exudate, and thus is not a major component in the resistant plant. 

ABSTRACT This review is concerned with non-isoprenoid phenolic lipids typified by compounds biosynthesised by the polyketide pathway. Botanical, biological and entomological sources of such phenolic lipids are described which contain monohydric phenols, notably cardanol and relatives, dihydric phenols such as cardols, alk(en)ylresorcinols,urushiols and phenolic acids, particularly anacardic acids. Some recently investigated mixed types of dihydric phenolic lipids are included. Separatory methods are briefly reviewed. Synthetic methods for the saturated and unsaturated members of the three main classes of interest in structure/activity studies are summarised. Biological properties of members of the three main classes are given and discussed. 

The first synthesis modelled on biomimetic lines was directed to obtaining anacardic acids by way of polyketides [237] and later to a (17 l)-orsellinic acid [43]. A less complicated approach based on the Michael addition of ethyl acetoacetate and ethyl octadec-2-enoate, has led to a C15 orsellinic acid, Fig (4)-56, 2,4-dihydroxy-6n-pentadecylbenzoic, considered to be the biogenetic precursor of the cashew phenols [238], notably cardol, by decarboxylation. The use of bromine at the aromatisation stage in this synthesis precluded the extension of the method to components with unsaturated side-chains, although bromination with copper(ii)bromide and thermal debromination offers an alternative procedure. In a more recent approach, by the use of an oxazole intermediate and its addition to ethyl acetoacetate, (15 0) and (15 1) anacardic acid have been obtained [239] as shown in Scheme 5a, b. The 8(Z),1 l(Z)-diene and 8(Z),1 l(Z),14-triene have also been synthesised [240] by way of ethyl 6-(7-formylheptyl)-2-methoxybenzoate (C), prepared from acyclic sources, rather than, as in previous work, by semisynthesis from the ozonisation of urushiol. 

A full biosynthetic pathway has to account for the simultaneous formation of cardol, 2-methylcardol, anacardic acid, some cardanol and for the different unsaturation pattern of anacardic acid and cardanol which are similar with a relatively low 40% of triene compared with cardol and 2-methylcardol where the the triene constituent is more than 75%. Scheme 1 summarises known ring formation stages and speculative ones. 

Although the mechanism of formation of unsaturation may well proceed as for the polyethenoid fatty acids, it is of interest that palmitoleic acid was not found to be incorporated (ref. 83). The conclusion was drawn that in the biosynthesis of anacardic acid, the side chain was in a different state of activation and/or site than in the case of the triacylglycerol lipids. Some of these of course are found in the oil in the cashew kernel. 

In the cardanol, cardol, urushiol and anacardic acid series, all of which have 8,11-unsaturation, two alternative synthons namely Cg and Cg units may be involved in alkyne routes for the formation of the second double bond. A summary is shown of alkyne, Wittig, and alkylation routes. 

TABLE 13.8 /oCOMPOSTTlON of UNSATURATED CONSTITUENTS of ANACARDIC ACID in NATURAL CNSL by DIFFERENT TECHNIQUES... 

Although HPLC analysis affords by virtue of its partition nature a very detailed analysis of natural and technical CNSL, it is of interest to compare compositional results obtained by other methods. By contrast, GLC is less detailed and TLC as an adsorption process, operating through functional groups, affords a very direct uncomplicated indication of the main components present. Not all areas in the world producing CNSL have access to HPLC or even GLC analytical procedures and other chromatographic techniques may in those circumstances be obligatory. Tables 7 and 8 show respectively the % composition of the main components and of the unsaturated constituents of anacardic acid in natural CNSL by several different techniques. 

Anacardic acids are 6-alkylsalicylic acids with different alkyl chain lengths and degrees of unsaturation. Cashew is the most important natural source of anacardic acids. Anacardic acids are found not only in cashew nut shell oil, but also in the nut and fruit juice made from cashew apple [20]. Anacardic acids are relatively nonpolar hydrophobic substances. Their structures are illustrated in Figure 10.1. They are insoluble in water, but well soluble in organic solvents such as ethanol or dimethyl sulfoxide (up to lOmg/mL). The cardanols might be formed by thermal decarboxylation of the anacardic acids [19]. 

Cashew nut shell liquid resin n. Resin derived fi om the liquid obtained from the shells of the nuts of the species, Anacardium occidentale, which grows chiefly in India and South America. The naturally occurring liquid is a mixture of a dihydroxy phenol cardol and anacardic acid. This acid readily decarboxylates on heating to yield a monohydroxy phenol with an unsaturated side chain, anacardol. 

Anacardic acids are mixtures of several analogue molecules with alkyl chains of 13, 15, 17 or 19 carbons and 0-3 unsaturations. It is the main cashew nut shell liquid component with cardol and can cause contact dermatitis in cashew-nut workers. 

Long-chain alkylphenols have been investigated extensively (33) by both adsorption and reversed-phase partition methods (34). The cashew phenols (from Anacardium occidentale) comprise cardanol (1), cardol (2), 2-methylcardol (3), and anacardic acid (4), each existing as a mixture of the saturated, 8 -monoene, 8 ,11 -diene, and 8 ,1 l ,14 -trieneconstituents. In ammoniated solvent [light petroleum-diethyl ether-ammonia (60 40 2)] the acidic compound anacardic acid remained practically on the baseline, whereas in an acidic solvent [light petroleum-diethyl ether-formic acid (70 30 1)] it migrated toward the solvent front as an intramolecularly bonded substance. In natural cashew nut shell liquid the phenols and their unsaturated constituents have the values 0.20 (cardol). 

---