Anacardic acid 8 -diene

Scheme 3 depicts, for anacardic acid diene, the synthesis of H, by the alkylation method with a Q4 halide and the synthesis of co-hydroxy C14 the side-chains for the 8,11-diene and its stereoisomers namely (A) 7Z,10Z, (B) 7Z,10E, (C) 7E,10E and (D) 7E,10Z.. The 1-iodo derivatives of each were obtained as for route (a). This methodology has been applied to the synthesis of Fig (2)-3, anacardic acid 8(Z),ll(Z),14-triene as shown in Scheme 4. Strategies for obtaining side-chains for the stereoisomers of the triene have been described [2,114].

However, on account of the unavailability of the corresponding aldehyde, anacardic acid (8Z)-monoene Fig (2)-2 and Fig (2)-3, the (8Z,llZ)-diene were obtained by the alkylation route as described in [2],... 

The initial application to the synthesis of anacardic acid-8Z,l lZ-diene, used the synthons, ArCi — ArC7 - ArCio — ArCis [114,236]. 

Scheme 3. Synthesis of anacardic acid 8(Z),1 l(Z)-diene and C14 reactant stereoisomers...

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. 

Anacardic acid 8(Z),1 l(Z)-diene has been prepared by the Diels-Alder addition of 1-methoxycyclohexa- 1,4-diene to an homologous propiolic ester [241] with elimination of ethylene. The methoxydiene intermediate was prepared by the Birch reduction of methoxybenzene and this approach represents a link between the use of an aromatic and a derived acyclic precursor. 

Constituents of natural cashew nutshell liquid (Anacardium occidentale) are active inhibitors of a-glucosidase, invertase and aldose reductase. The saturated, monoene, diene and triene anacardic acid constituents were the most potent inhibitors compared with commercially structurally-related compounds which showed a negligible activity [283]. 

However, 1-methoxy-1,3-bistrimethylsjloxybuta-1,3-diene and the same dienophile afforded a mixture of products (A and B) in low yield. The final step for formation of the required anacardic acid, 2-methoxy-6-pentadecylbenzoic acid, was to be effected by catalytic hydrogenolysis of the unhindered hydroxy group by formation of the ether with 5-chloro-1-phenyltetrazole (refs.124,125). 

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). 

---