Unsaturated isobutylamides

Some of the plants belonging to the families Compositae and Rutaceae contain the insecticidally active isobutylamides of unsaturated, straight-chain acids with 

10-18 carbon atoms. Of these, the most important are pellitorine (46), anacycline (47), spilanthol (48), herculine (49), fagaramide (50) and piperlongumine (51). 

Early investigations of compounds of this type are linked with the names of Bucheim (1876), Dunstan and Garnett (1895) and Schneegans (1896). Using modern methods of structure investigation, Crombie et al. (Crombie and Harper, 1949 Crombie, 1952 1955 Crombie and Manzoor-i-Khuda, 1956 1957), Jacobson (1950 1953), La Forge et al. 1942 La Forge and Barthel, 1944), Fish and Waterman (1972), Su and Horvat (1981), Oriowo (1982), as well as Kubo et al. 

Their insecticidal action is manifested by a rapid knockdown effect, which is characteristic also of pyrethrines. A further property in common with pyrethrines is their pungency, which together with their unsatisfactory stability has prevented their general use in practice, in spite of their strong insecticidal action. 

---

Jacobson, M., The unsaturated isobutylamides, in Naturally Occurring Insecticides (M. Jacobson and D. G. Crosby, eds.), 137-176, Marcel Dekker, Inc., New York, 1971. 

Jacobson, M. 1971. The Unsaturated Isobutylamides. In Naturally Occurring Insecticides, Jacobson, M., and Crosby, D. G., eds. New York, Marcel Dekker. pp. 137-149. 

Miyakado, M., Nakayama, L, and Ohno, N. 1989. Insecticidal Unsaturated Isobutylamides. In Insecticides of Plant Origin, Aranason, J. T., Philogene, B. J., and Morand, R, eds. ACS Symposium Series, 387. Washington, DC, American Chemical Society, pp. 173-187. 

Previous work with extracts of various plant species containing isobutylamide compounds indicated the larvicidal effects of the extracts against several species of mosquito.Other work has shown the molluscicidal activity of some unsaturated aliphatic isobutylamides against Physa occidentalis. 

The 13CNMR data show a characteristic carbonyl carbon at 166 ppm, which corresponds to the carbon attached to the nitrogen via an amide bond. The aliphatic carbon signals can be found between 19 47 ppm for the isobutylamides and 11 15 ppm for the 2-methyl-butylamides. The carbon signals associated with the double and triple bonds of the unsaturated chain can be found between 119-136 and 64-77 ppm, respectively. For additional information regarding 13CNMR, see Perry et al. (1997). 

In attempting to find versatile and general synthetic approaches to unsaturated lipid isobutylamides, Crombie [133] investigated the relative merits of a number of methodologies for the preparation of 2E, 4E -8-hydroxyoctadienoic acid isobutylamide and other potentially useful synthons. 

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]. 

Unsaturated Amides. In 1971, a group of pungent compounds (isobutylamides) obtained from members of the families Compositae and Rutaceae were described by Jacobsen (Jacobsen, 1971) to have limited use as insecticides. The compounds were characterized as unstable with a marked tendency to polymerize. Examination of extracts of the fruit of the black pepper Piper nigrum, using the aduzki bean weevil as a bioassay, resulted in the isolation of three isobutylamides (13-15) which displayed insecticidal activity (when combined equimolarly) to the pyrethrins (Miyakado et al., 1983, 1989). Based upon the observations of Miyakado and earlier reported test results for synthetic analogs of the compounds described by Jacobsen, Elliot and co-workers defined a basic amide structure to... 

---