Solenopsis alkaloids

A rapid GC-FT1R method for determination of the cis or trans configuration of 2,6-disubstituted piperidines was developed using, among others, the Solenopsis alkaloids 198a, 198b, 202 and the Monomorium alkaloids 207-209 [480]. A method for determination of the absolute configuration of Solenopsis alkaloids was developed, in which the amines are... 

Both foraging and feeding were stimulated by not providing the ant colonies with food for 48 hours. Food was then offered to the ants as droplets of honey to which were added 1 or 2 pg of alkaloids in 2 pi of absolute ethanol. In one study, both treated droplets and colonies were randomized for each replicate which compared the repellencies of four alkaloids that included a Solenopsis alkaloid, trans-6-tmdecyl-2-methylpiperidine (36), two Monomorium dialkylpyrrolidines Solenopsis... 

Besides piperidine alkaloids, a total of 19 pyrrolidines have been found in the secretions of thief ants and fire ants of the genera Solenopsis and Monomorium. Among these, compounds 80-84 are simple pyrrolidines with two saturated linear all-carbon side chains only in Solenopsis latinode is there a secondary amine (82) and its methylated analog (85). One or two terminal unsaturations are present in compounds 86-91, which all possess a (hex-l-en)-6-yl chain and a 5-, 7-, or 9-carbon saturated chain. Compounds 93, 94, 96, 97, and 98 are the A-l-pyrrolines corresponding to pyrrolidines 80, 82, 90 (93 and 96 corresponding to 80, 94 to 82, and 97 and 98 to 90). 

Several species pertaining to the sub-family Myrmicinae (e.g., Solenopsis spp., Monomorium spp.) are characterized by a venom rich in dialkylated saturated nitrogen heterocycles (e.g., piperidine, pyrrolidine, indolizidine, pyrrolizidine). Exhaustive lists of these alkaloids have already been published [114-116]. Since then, only a few more of these alkaloids have been reported from a few further species. 

Examination of the venom content of the workers of Solenopsis maboya revealed the presence of (5Z,9Z)-3-butyl-5-methylindolizidine (107), (5E,9E)-3-butyl-5-methylindolizidine (108) and frans-2-methyl-6-nonylpiperidine (109), while analysis of the extract of the queens revealed the presence of a single alkaloid, ris-2-heptyl-5-methylpiperidine (110) (Fig. 19) [117]. Such caste-specific alkaloidic contents has been already been found in other Solenopsis ants [ 118,119] and suggest different roles for these compounds in each caste. 

It had been already reported, that the venom of the fire ant Solenopsis invicta is composed of 2-methyl-6-alkyl- or 2-methyl-6-alkenylpiperidines,the carbon chain of which has an odd number of carbon atoms in the range of 11 to 17 [ 115, 116]. Recently, Deslippe and Guo [120] reported that in workers of S. invicta from Texas the relative abundance of each alkaloid was highly correlated with worker size as well as with the ratios of saturated to unsaturated alkaloids. Moreover, young and old workers produced less venom than ants of intermediate age... 

In an effort to identify possible sources of the 16 alkaloids found in the skin of the Panamanian poison frog Dendrobates auratus, ants from a total of 61 terrestrial nests were analyzed [124]. The alate queens of one species of myr-micine ants (Solenopsis (Diplorhoptrum) sp.) collected at Cerro Ancon were found to contain the decahydroquinoline (-)-ds-195A (112) which was also present as a minor alkaloid in the skin of the microsympatric population of D. auratus. Moreover, from wingless ants of two nests collected at Isla Taboga and identified as Megalomyrmex silvestrU the same workers isolated the stereo-isomeric 3,5-disubstituted pyrrolizidines rfs-251 K (117) and trans-251 K (118) in the same ratio 3 1 that was present in the skin of a microsympatric population of D. auratus (Fig. 20) [124]. 

Venoms from the fire ants Solenopsis invicta and 5. geminata are free of detectable histamine but possess histamine-release activity. This activity can account for the edema, itch, redness, warmth, and possibly the pain and burning sensations resulting from fire ant stings. And it can be attributed to the piperidines which constitute the major component of the venom. It has actually been proved that 6-methyl-2-n-undecylpiperidines (Ic and Id), components of S. geminata, possess the histamine-release activity (75). Due to some of the above-mentioned various activities the piperidine alkaloids play roles as defensive compounds. In addition to 2-alkyl-6-methylpiperidines, their N-methyl derivatives (3) are found in S. pergandei, S. carolinensis, and S. conjurata, and 1-piperideine derivatives (6 and 7) in S. sp. A (Puerto Rico) and S. xyloni (Table I). 

Solenopsis (Diplorhoptrum) conjurata and some other thief ants contain indo-lizidines and/or piperidines (Tables I and II). (5Z,8 )-3-Heptyl-5-methylpyr-rolizidine (48) has also been shown to be contained in the thief ant Solenopsis xenovenenum (Table IV). The poison glands of Aphaenogaster fulva and A. tennesseensis contain the tobacco alkaloid anabaseine (8), which functions as an attractant in A. fulva (Table I) (26). 

Alkaloid parsimony has also been detected in animals that produce alkaloids. Fire ants in the genus Solenopsis produce venoms dominated by novel 2,6-dialkylpiperidines that are delivered into vertebrates subcutaneously. The venoms constitute outstanding examples of alkaloid parsimony as they provide their ant producers with a diversity of deterrents. The alkaloids cause dermal necrosis in humans and are very algogenic in addition to being very lytic. The piperidines also perturb enzymatic pathways and block neuromuscular junctions. Fire ants have obviously adapted their piperidines to function as extreme exanples of alkaloid parsimony. 

More than a dozen 2,5-dialkylpyrrolidines have been identified in the venoms of Solenopsis and Monomor ium species (J7) AH of these compounds are of the trans configuration. Whereas Solenopsis species may produce only one compound in their poison glands, the venoms of Monomorium species generally consist of mixtures of these alkaloids. 

The cis-trans isomers of four 2-alkyl-6-methylpiperidines, in which the alkyl groups consist of relatively long alkyl chains (C9-Ci5), have been identified in fire ant venoms (XI) (15, 17) members of each Solenopsis (Solenopsis) species group appear to produce characteristic alkaloids. The presence of a fifth 2-alkyl-6-methylpiperidine, 2-hepytl-6-methylpiperidine, in the venom of queens of S. richteri is indicated by mass spectral data (20). ... 

Two N-methyl-2,6-dialkylpiperidines (XII) have been identified in the venoms of two Solenopsis (Diplorhoptrum) species (6). These alkaloids, which are minor concomitants of the corresponding nordialkylpiperidines, are present as trans-isomers. 

In contrast to the dialkylpyrrolidine theme that characterizes the venoms of many Solenopsis (Diplorhoptrum) species (6), that of 3. xenovenenum is distinctive in containing a pyrrolizidine as the sole alkaloid. and C NMR spectroscopy show... 

The disubstituted pyrrolidines and piperidines have been demonstrated to be excellent repellents for ants under field conditions. Workers of Monomorium pharaonis effectively repel other species of ants with venom droplets which accumulate on the tip of the sting (37), a strategy that is used with equal success by workers of North American Monomorium species ( 38.) and the European thief ant, Solenopsis fugax (37). The venom of the latter species contains a single alkaloid, trans-2-butyl-5-heptylpyrrolidine (I, m=3, n=6) (1 ), and the... 

Solenopsis ants produce piperidine alkaloids which resemble the plant alkaloid coniine. These alkaloids are strong deterrents and inhibit several cellular processes, such as electron transport chains (Table IV) 28,494). Many insects indicate the content of toxic natural products by warning colors (aposematism) or by the production of malodorous pyrazines 4,17,231,494). 

Disubstituted indolizidines, unlike many classes of amphibian alkaloids, are not unique to amphibians. 3,5-Disubstituted indolizidines such as monomorine I [(5Z,9Z)-195B] occur in ants of the genera Monomorium and Solenopsis (125,129,134). Some of the ant indolizidines are as follows (5Z,9Z)-3-n-butyl-5-methylindolizidine (monomorine I), (5Z,9Z)-3- -ethyl-5-methylindolizidine, (5Z,9Z)-3-hexyl-5-methylindolizidine, and (5 ,9Z)-3-butyl-5-(4-pentenyl)indolizidine. A series of 5-substituted indolizidines, the piclavines, were reported recently from a marine tunicate (Clavelina picta) (135). 

Disubstituted piperidines (and piperideines) are well known as constituents of myrmicine ant venoms, particularly in fire ants of the genus Solenopsis (125,134,149,161,164). Both cis and trans isomers occur. Cis-and/or rrans-2-methyl-6-nonylpiperidines are prominent ant alkaloids. These ant alkaloids have not been detected in amphibians, but the 4-hydroxy piperidine analog (241D) has. 

Three new diastereomers of 3-hexyl-5-methylindolizidine, (5Z,9Z)-, (5E,9E)- and (5Z,9 ), Fig. (8), were identified in different collections of thief ants Solenopsis (Diplorhoptrum) species from Cahfomia. The identification of these alkaloids resulted from the analysis of their MS spectra and comparison of their GC-FTIR spectra. The authors also emphasised the chemotaxonomic value of the stereochemistry of these alkaloids [23]. 

---