Alkamides isolation

Clifford, L.J. et al., Bioactivity of alkamides isolated from Echinacea purpurea (L.) Moench, Phytomedicine, 9, 249, 2002. 

FIGURE 8.2 Example of four alkamides isolated from Echinacea. 

The distinctive feature from alkamides isolated from Piperaceae family is the presence of an aromatic ring, commonly a 3,4-methylenedioxyphenyl group (although p-methoxyphenyl and 3,4,5-trimethoxyphenyl have also been found) linked to the end of an unsaturated C3-C16 fatty acid chain [20]. The amine group commonly found is an A-isobutyl, pyrrolidinyl, or piperidinyl group. Fig. 4 [21-23]. 

FIGURE 20 AfHiun-ielated alkamides isolated frcmi Heliopsis longipes. 

Polyunsaturated alkamides have been isolated from Aaronsohnia, Achillea, Anacyclus, and Echinacea species. Due to the structural similarity of alkamides to arachidonic acid, it is likely that alkamides act as competitive inhibitors of COX and LOX enzymes. At a concentration of 50 pg/ml, all twenty tested alkamides from Achillea and Echinacea species showed 21-... 

PHARMACOLOGICAL EFFECTS The type of extract or preparation can be important since alcoholic extracts are unlikely to contain polysaccharides, whereas aqueous extracts may not contain the lipophilic alkamides. Tests have been performed with the pressed juice, alcoholic extracts and isolated pure compounds. Effects such as increased phagocytosis as measured by the carbon clearance test, macrophage activation,... 

Alkamides from the roots of Echinacea purpurea were isolated and separated on a 45°C Cjg column (A = 263nm). A complex 35-min 55/45 ->0/100 water/ acetonitrile gradient was used. Two major components were identified undeca-(2 ,4Z)-diene-8,10-diynoic acid isobutylamide and dodeca-(2 ,4 ,8Z,10Z)-tetra-enoic acid isobutylamide [1092]. At least nine other related compounds were isolated and identified as alkamides. Detection limits for the major components were reported as 15ng injected (S/N = 5). 

In total, 15 alkamides have been identified in . angustifolia roots as major lipophilic constituents [23-25]. They are mainly derived from undeca- and dodeca-noic acid, and differ in the degree of unsaturation and the configuration of the double bonds (Fig. 2). The predominant structural type is a 2-monoene-8,10-diynoic acid isobutylamide, but also some 2 -methyl-butylamides have been found. The main constituents are the isomeric dodeca-2 ,4 ,8Z,10 /Z-tetraenoic acid isobutylamides. In addition, the isobutylamides of undeca-2Z-en-8,10-diynoic acid, dodeca-2 -en-8,10-diynoic acid, dodeca-2 ,4Z-dienoic acid and hexadeca-2 , 9Z-dien-12,14-diynoic acid, as well as the 2 -methyl-butylamides of undeca-2Z-en-8,10-diynoic acid and dodeca-2 -en-8,10-diynoic acid were found in lipophilic extracts of . angustifolia roots. Another constituent, undeca-2 -en-8,10-diynoic acid isobutylamide, has already been isolated from Acmella ciliata [26]. The isobutylamides of undeca-2 ,4 -dien-8,10-diynoic acid, undeca-2Z, 4 -dien-8,10-diynoic acid and dodeca-2 ,4Z-dien-8,10-diynoic acid are present only in very low concentrations in . angustifolia roots, but were found as major constituents in the roots of . purpurea (Fig. 9) [25, 27]. 

Eleven alkamides have beeen identified in Echinacea purpurea roots [24, 77]. In contrast to . angustifolia, most of these alkamides possess a 2,4-diene moiety. Bohlmann and Grenz [24] isolated a mixture of two dodeca-2,4,8,10-tetra-enoic acid-isobutylamides, whose stereochemistry was not determined, as well as undeca-2Z,4 -dein-8,10-diynoic acid-isobutylamide and dodeca-2Z,4 -dien-8,10-diynoic acid-isobutylamide. Bauer et al. [77] found a series of alkamides which were identified as the isobutylamides of undeca-2 ,4Z-dien-8,10-diynoic acid, dodeca-2 ,4Z-dien-8,10-diynoic acid, dodeca-2 ,4 ,10 -trien-8-ynoic acid and dodeca-2 ,4 ,8Z-trienoic acid, as well as the 2 -methyl-butylamide of dodeca-2 ,4Z-di-en-8,10-diynoic acid. The main compounds, already isolated by Bohlmann and Grenz [24], were shown to be the isomeric mixture of dodeca-2 ,4 ,8Z,10 /Z-tetraenoic acid isobutylamides. A further compound, undeca-2 ,4Z-dien-8,10-diynoic acid-2 -methyl-butylamide had already been described as a constituent of Acmella ciliata [78]. Alkamides could also be produced in transformed callus and... 

Another isocoumarin, artemidinol, has also been reportedly isolated from tarragon Fractionation of cell tissue extract of A. dracunculus guided by human benzodiazepine receptor binding leads to the isolation of delorazepam and temazepam at concentrations ranging 100-200 ng/g. This is the first report on the presence of such compounds in plant cells. The aerial parts contain the alkamides, pellitorine, and neopellitorine A and B. The latter two were isolated as new compounds from A. dracunculus ... 

Four genuses from the Rutaceae family produce alkamides Evodia, Pleiospermium, Zanthoxylum, and Glycosmis, the latter two being the most productive. More than 50 aliphatic [24,25] and aromatic [5,26] alkamides have been isolated from Zanthoxylum genus, which are responsible for its... 

Finally, alkamides with both add and amine aromatic residues have been isolated from plants of several other families, like Euphorbiaceae, Annonaceae, Rutaceae, Convolvulaceae, Menispermaceae, Brassicaceae, Aristolochiaceae, etc. These alkamides possess a phenethyl group on the amine residue, with cin-namoyl or benzoyl groups as the acid group, Fig. 7 [17]. 

Another specie used as anesthetic is Acmella decumbens and its content of alkamides has been established [183]. On the other hand, the anesthetic aUca-mide (2 ,4 ,8Z,10 )-W-isobutyl-2,4,8,10-dodecatetraenamide was isolated from the toothache plant Acmella oleracea and at least from nine other plants (Fig. 21) [184]. 

Decades of investigations in the natural products chemistry of the Piper genus yielded an important amount of monomeric and dimeric alkamides of diverse molecular architectures crnitributing to their biological activities [20-23,203,208-219]. Specifically, [4+2] dimers were isolated in P. chaba while [2 + 2] dimers were isolated in P. nigrum and P. longum, in both cases together with monomeric amides. 

Alkamides that are used as spice and to produce anesthetic effects have also been isolated from other species. These alkamides have been isolated from Ottonia propinqua [231,232], O. frutescens [233], and Matricaria pubescens [234]. 

Alkamides are alkaloids of restricted distribution in plants. Although they have been isolated in more than 35 family plants, their presence is usually limited to obtain the individual alkamides in only a few milligrams. However, they are the most abundant components in Asteraceae, Solanaceae, Rutaceae, and Piperaceae families. Even within these four families, their presence is restricted to a few genera included within Anthemideae and Heliantheae tribes in Asteraceae, Capsicum in Solanaceae, Zanthoxylum and Glycosmis in Rutaceae, and Piper in Piperaceae. Stmcturally, alkamides possess an acidic and an amino moieties. Both acidic and amino moieties are characteristic depending on the plant family. 

Today, more than 300 alkamides have been isolated as natural products and more than 100 of their synthetic analogs have been prepared. A large variety of biological activities have been described for these compounds. However, three activities are predominantly important analgesic attributed to the alkenylamides isolated from some Asteraceae, Capsicum and Piper species immunomodulatory associated to the characteristic W-alkynylamides found in some of the Asteraceae plants and antifungal and insecticidal shown for the sulfurated alkamides from Glycosmis. 

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