Resorcinolic lipids

Kozubek, A., Tyman, J. Resorcinolic lipids, the natural non-isoprenoid phenolic amphiphiles and their biological activity. Chemical Reviews, Vol.99, No.l. Qanuary 1999), pp. 1-31, ISSN 0009-2665... 

For resorcinolic lipids, particularly those with long saturated side-chains, the use of polar solvents is important due to their amphiphilicity. The crude extracts in many cases are subjected to preliminary fractionation/purification either by solvent fractionation/partition or by application of chromatography. For prepurification of the material and its separation from polymerized phenolics, gel filtration on hydrophobic Sephadex or TSK gel is sometimes used. Silica gel is most frequently employed for the separation and/or purification of resorcinolic lipids, notably in some studies with Ononis species (12-14). The array of compounds reported appears partly attributable to methylation or acetylation reactions occurring during column chromatographic separation. An interesting approach for I the pre-purification and selective separation of resorcinolic lipid from phenolic lipids or resorcinolic lipids from impurities has recently been reported. A selective partitioning of different non-isoprenoid phenolic lipids... 

AR occur in cashew nut shells as a fraction of other oil components like cardols, cardanols and anacardic acid. A comparative study on the extraction of cashew nut shell liquid (CNSL) was presented by Shobha and Ravindranath (50). The study involved the extraction of the cashew nut shell by supercritical CO2 or pentane. The pentane extraction was carried out on 50g steamed or fresh cashew nut shells in lOOmL solvent. Supercritical CO2 extraction was performed on 300g freshly broken cashew nut shells at 25 MPa and 40 C with the CO2 flow kept at 4-5Kg/h for 17,5h with extract collection every 2.5h. The resorcinolic lipid fraction obtained by supercritical CO2 represented 82% of the equivalent obtained by pentane extraction of fresh cashew nut shells and 70% of the extraction of steamed material. Despite this appreciable variation on the ratio of the total cardols and cardanols from one mediod to other, the relative proportion of the enomers in each group was very similar (50). Generally, the extraction yield obtained by supercritical CO2 was lower (= 60%) than that obtained by the classical solvent extraction methods (50), however, the product was nearly colorless. One of the major problems in the industrial application of CNSL is the very dark brown color of the solvent extracted product. 

Dihydric phenolic lipids of the cardol type are the most abundant in plant, fungal and bacterial kingdoms. The first species in which the members of the title subclass of phenolic lipids, resorcinolic lipids, were found was Ginkgo biloba (Ginkgoaceae) [6,9,10,17]. Later, the presence of resorcinolic lipids (5-n-alk(en)ylresorcinols) was shown also in other species, first, in the Anacardiaceae [14], which is an important source of various phenolic lipids, not only of alkylresorcinols but also of alkylphenols and alkylcatechols. For example, the cashew and the processing of cashew nuts are the main source of phenolic lipids for the formaldehyde-polymer industry. Aspects of Anacardium occidentale in relation to synthesis, semi-synthesis and chemical industry have been reviewed Tyman [1,11,14] as well as a recent book [2]. 

Another plant family in which the occurrence of resorcinolic lipids was demonstrated is the Gramineae family. The pioneering work of Wenkert has demonstrated the existence of substantial amounts of 5-n-alkylresorcinols in wheat bran [93]. Later, the occurrence of resorcinolic lipid in rye [94] and barley [95] has been shown, compared with other families [96-98] and also shown among lower plants. A number of further studies have been concerned with the determination, localization and characterization of various resorcinolic lipids present in cereal grains [99-103]. Later, the occurrence of resorcinolic lipids has been demonstrated in an increasing number of plant sources. 

Higher plant resorcinolic lipids include very simple homologues of the orcino 1-type (l,3-dihydroxy-5-methylbenzene) phenols and a variety of homologues that are derivatives with the ring, chain or both ring and chain modified. Resorcinolic lipid molecules have a dual, aromatic and acyclic character. In most cases the side chain in resorcinolic lipids is odd numbered, which is relevant with regard to their possible biosynthetic pathway. 

Since 1969 the existence of resorcinolic lipids has been demonstrated in microbial organisms [24]. Leprosols, are resorcinolic lipids derivatives which have been identified in Mycobacterium leprae. Later the occurrence of simple 5-alkylresorcinols has been demonstrated in strains of soil bacteria from Azotobacter [104-107] and Pseudomonas families [104-111]. Bacterial resorcinolic lipids have been thought to be related exclusively to the transformation of vegetative cells into their dormant forms, cysts [106]. However, our previous studies on other Azotobacter and Pseudomonas strains [107], as well as recent, unpublished data indicate the occurrence of resorcinolic lipids also in vegetative cells, non-... 

The amount of resorcinolic lipids in plant and microbial sources varies considerably depending on the source. The most prominent source of resorcinolic lipids (cardol and methylcardol), as well as of other phenolic lipids, is the oil obtained from extraction of the shell of cashew nuts, Anacardium occidentale, (up to 20% of resorcinolic lipids). The oily extract from the roasting of cashew nuts (Cashew Nut Shell Liquid) is one of the most important sources of these compounds for formaldehyde polymerisation in industry [1,2,11,114], Other plant sources contain amounts of resorcinolic lipids that vary from 0.01% to 0.1% with rye grains as the richest [101,115-120] while bacterial sources, depending on the family and strain contain up to 6% of various resorcinolic lipid derivatives [105]. 

The structures of over 120 identified natural resorcinolic lipid homologues are presented in Table 4 and Fig. (4) which lists the formulae of resorcinolic lipids and relevant references to previous and current studies. 

It is worth noting that in many cases some of the resorcinolic lipids present in biological material still remain structurally uncharacterised. For instance, chromatographic analysis of acetone extracts from cereal grains shows the presence of at least 4 other components that probably belong to the group of resorcinolic lipids. Two of them have been identified as 5-(2-oxoalkyl) resorcinol and 5-(2-oxoalkenyl) resorcinols [178] and the another as a 5-(2-hydroxyalkyl) resorcinol [181]. 

Similarly to their antibacterial activity, resorcinolic lipids exhibit fungistatic properties. However, experiments indicate that resorcinolic lipids inhibit the growth of Trichophyton mentagrophytes and Saccharomyces cerevisiae to a lower degree than observed for bacteria. No activity was shown against Candida albicans and Asperigullus niger [256]. The occurrence of 5-n-(heptadec-12-enyl) and 5-n-... 

Experimental data together with the fact that resorcinolic lipids are nontoxic to higher animals, for example, they are tolerated by rats with an oral intake of 5g/kg ([204] and Kozubek, unpublished work) has resulted in the application of these compounds, as basic components in pharmaceutical and cosmetic preparations. These preparations were found to be useful in the treatment of mouth and gingival infections, as antifungal fluids, in antiacne and also in hair restoration-lotion preparations [309,312,314]. 

Resorcinolic lipids as growth regulators and in host-parasite relationship... 

Recent experimental data have also shown that resorcinolic lipids, including alkylresorcinols and their derivatives at a concentration level of micrograms/ml inhibit competitively the reverse transcriptase of mice leukemia viruses and avian myeloblastosis [338,339]. 

These results and those now discussed which show the ability of resorcinolic lipids to incorporate and modulate phospholipid bilayer properties, suggest a possible similar role in biological membrane-related enzymatic activities. It has been demonstrated that at a concentration of 10 5 M, long-chain resorcinolic lipids, caused a decrease of apparent acetylocholinesterase activity in the erythrocyte membrane while simultaneously stimulating the activity of Ca2+-dependent ATPase [348]. The inhibition of erythrocyte acetylcholinesterase has been also observed for other phenolic lipids (Stasiuk and Kozubek - unpublished work) and a similar effect of one of the homologues, namely tridecylresorcinol shown towards Na+-K+ ATPase [157]. a-Glucosidase and aldolase were also inhibited by resorcinolic lipids isolated from cashew [283]. 

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