Dodeca-3,6,9-trienoic acid

FIGURE 3 Cn hydrocarbons from dodeca-3,6,9-trienoic acid. Loss of C(l) and a single hydrogen from C(5) yield the acyclic hydrocarbon finavarrene. Decarboxylation and loss of a single hydrogen from C(8) results in (6S)-ectocarpene. No other hydrogen atoms are lost during the biosynthetic sequence. 

FIGURE 5 Biosynthesis of Cla hydrocarbons in higher and lower plants. The similar pattern of functionalization of dodeca-3,6,9-trienoic acid and 9-HPEPE is shown. 

Interestingly, the first biosynthetic experiments with [3H]linolenic add and the terrestrial plant Senecio isatideus (Asteraceae) as a model system for the biosynthesis of algal pheromones were unsuccessful. If, however, labeled dodeca-3,6,9-trienoic add is administered, a rapid transformation into ectocarpene takes place (36). Nevertheless, the C12 add ultimately derives from linolenic acid via three /3-oxidations, since labeled tetradeca-5,8,11-trienoic acid, which requires only one /3-oxidation, is converted into labeled ectocarpene albeit with very low effidency (37). 

To date, only one study has evaluated the pharmacokinetics of the alkamides contained in the Echinacea products administered to humans (27). Subjects (n - 11) received a single oral 2.5-mL dose of the 60% ethanolic extract from E. angustifolia roots or placebo (60% ethanol). Six different alkamides were analyzed (1) Undeca-2D/Z-ene-8,10-diynoic acid isobutylamides (2) Dodeca-2D,4Z-diene-8,10-diynoic acidisobutylamide (3) Dodeca-2E-ene-8,10-diynoic acid isobutylamide (4) Dodeca-2E,4E,8Z,10E/ Z-tetraenoic acid isobutylamides (5) Dodeca-2E,4E,8Z-trienoic acid isobutylamide and (6) Dodeca-2E,4E-dienoic acid isobutylamide. The extract contained approx 2.5 mg of (4), and approx 0.5 mg of all other components. The Cmax and area under the curve (AUC) for (4) were approx 10-fold that achieved with each of the other components. Thus, despite a fivefold higher amount per dose, the 10-fold greater Cmax and AUC achieved with (4) suggest it exhibits a greater bioavailability than the other components. 

Because commercial drug preparations involving the roots of Echinacea purpurea (Asteraceae) were frequently adulterated with the roots of Par-thenium integrifolium, a reexamination of this source of insecticidal and immunostimulatory active material has been carried out. Five new alk-amides have been isolated, and their structures were determined as undec-2 ,4Z-dien-8,10-diynoic acid isobutylamide (114), dodeca-2 ,4Z-dien-8,10-diynoic acid isobutylamide (115), dodeca-2 ,4 ,10 -trien-8-ynoic acid isobutylamide (116), dodeca-2 ,4 ,8Z-trienoic acid isobutylamide (117), and dodeca-2 , 4Z-dien-8,10-diynoic acid 2-methylbutylamide (118) by MS, IR, and NMR spectroscopic techniques (96). (See Fig. 11.)... 

According to the literature [28, 23], the roots of . angustifolia contain 0.01% of a polyunsaturated alkamide echinacein (dodeca-2 ,6Z,8 ,10 -tetraenoic acid isobutylamide), which has never been detected since. Greger [29] also doubts that a compound with the structure quoted (= neoherculin) occurs in Echinacea. Verelis [20] found the isobutylamides of dodeca-2 ,4 -dienoic acid and deca-2 ,4 ,6 -trienoic acid in . angustifolia roots , but it can be suspected that he has examined . pallida. 

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... 

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