Ant venoms

The veom of fire ants (genus Solenopsis) contains 2,5-dialkylpiperidines. Typically these bear a methyl group at C-2 and a long alkyl or alkenyl chain at C-6. Some examples from S. saevissima are structures (114) and (115) where n=lO, 12 and 14 and (116) and (117) (where n=3 and 5 (J.G. MacConnell, M.S. Blum and H.M. Fales, Tetrahedron, 1971, 27, 1129). In addition some of the bases occur naturally as the A -nitroso derivatives. 

An interesting investigation was carried out to ascertain if there are differences in the alkaloidal composition of the venoms from worker and soldier ants and also between those of red and black races, and it was found that in some cases there is indeed a variation. Thus in red forms of S. saevissima trans-isomers predominate, whereas in the venom of black ants mixed cis and trans-isomers are present, although structures (114,n=14) (115,n=14), (114,n=5) and (115,n=5) are only minor components (J.M. Brand et al., Toxicon, 1972, 10, 259 Insect Biochem., 1973, 3, 45). 

Actinidine (92), a plant alkaloid (see section 8), is also a minor component of the defence secretion of the Australian cock-tail ant Iridomyrmex nitidceps (G.W.K. Cavill et al.. Tetrahedron, 1982, 38, 1931), a fact which indicates that ants may obtain toxins (or at least their precursors) from dietary sources. Actinidine has been synthesised (M. Nitta, A. Sekiguchi and H. Koba, Chem.Letters, 1981, 933). Anabaseine (118), a dihydro derivative of anabasine a well known tobacco alkaloid, is present in the poison glands of Aphaenogaster ants for which it also an attractant (J.W. Wheeler et al.. Science, 1981, 211, 1051). Ants from Puerto Rico produce the simple tetrahydropyridine (119) (T.H. Jones, M.S. Blum and 

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The most common example is acetic acid, CH3COOH (7), the acid that gives vinegar its sharp taste. Formic acid, HCOOH (8), is the acid of ant venom. 

All anions that are the conjugate bases of weak acids produce basic solutions. For example, formic acid, HCOOH, the acid in ant venom, is a weak acid, and so the formate ion acts as a base in water ... 

In many titrations, one solution—either the analyte or the titrant—contains a weak acid or base and the other solution contains a strong base or acid. For example, if we want to know the concentration of formic acid, the weak acid found in ant venom (1), we can titrate it with sodium hydroxide, a strong base. Alternatively, to find the concentration of ammonia, a weak base, in a soil sample, titrate it with hydrochloric acid, a strong acid. Weak acids are not normally titrated with weak bases, because the stoichiometric point is too difficult to locate. 

Milne RW, Aulfrey SJ, Heddle RJ Myrmeciapilosula (jack jumper) ant venom identification of allergens 33 and revised nomenclature. Allergy 2007 62 437-443. 

Two examples of synthesis of ant venom alkaloids via the Seebach (162) W-nitroso methodology have been published (163, 164). They start with N-nitrosopyrrolidine (125), which is sequentially alkylated at positions 2 and 5 (Schemes 14 and 15). 

Schmidt JO (1986) Chemistry, pharmacology, and chemical ecology of ant venoms. In Piek T (ed) Venoms of the Hymenoptera biochemical, pharmacological and behavioural aspects. Academic Press, London, p 425... 

Chiral rra s-2,5-dialkylpyrrolidines, which were used for the synthesis of ant-venom pyrrolizidines, were prepared in the following manner, d-Alanine was transformed into an pentenylamine which, upon intramolecular amidomercuration, yielded 15 (90TA561 92JOC4401). From a protected AA amide, after a Grignard reaction and treatment of the aminoketone with ethyl acetoacetate, the tetrasubstituted pyrrole 16 was obtained [93H(35)843],... 

The fire ant causes damage to a variety of crops and attacks livestock and human beings. The fire ant venom, secreted at the sting to human beings, is a potent necrotoxin, producing edema, pustule, and necrosis (5), and in addition possesses pronounced hemolytic (6), phytotoxic (7), insecticidal (5), antibac-... 

Another important class of organic compounds that we shall meet frequently, even in the early chapters of the text, are the carboxylic acids. These compounds are characterized by the carboxyl group, — COOH (7). As their names suggest, these compounds are acids. The most common example is acetic acid, CH3COOH (8 formally, ethanoic acid), the acid that gives vinegar its sharp taste. Another simple carboxylic acid is formic acid, HCOOH (9 formally, methanoic acid), the acid of ant venom. Note how the systematic (formal) names of the carboxylic acids are derived from the parent hydrocarbons (ethane and methane, respectively) by adding -anoic acid as a suffix to the stems eth- and meth-. 

A synthesis of arecoline (17) from acetaldehyde has been described.17 Sederine (18) is a minor base occurring in Sedum acre-, its structure has been settled by spectral and chemical study, but its stereochemistry has yet to be established.18 A new total synthesis of racemic solenopsin A (19) (fire-ant venom) has been published the pathway is outlined in Scheme 2.19... 

Both possible isomers of the 2,5-dialkyl-1-pyrrolines have been identified in the venoms of Solenopsis and Monomorium species. These compounds generally accompany the corresponding dialkylpyrrolidines as venom constituents. The venom of 3. punctaticeps, an African species, contains both 61- and -pyrrolines (VII) (j3) as do the venoms of three North American Monomorium species (12 ). The latter dialkylpyrrolines (VIII) are distinguished by the presence of two terminally unsaturated side chains. The pyrrolines in the venom of M. latinode are distinctive in constituting the only 5-pyrrolines (IX) in ant venoms that are not accompanied by the 1-pyrrolines (6). 

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). ... 

A wide variety of activities have been demonstrated for the alkaloids identified in myrmecine ant venoms, indicating that these small nitrogen heterocycles have been adapted to subserve multiple functions. Both the piperidines and pyrrolidines possess diverse pharmacological activities (reviewed in 1), and it seems likely that their roles in regulating both intra- and interspecific interactions are very significant. 

The 2,5-disubstituted pyrrolidines (and pyrrolines) are well known as constituents of ant venoms, particularly ants of the myrmicine genera Solenopsis, Monomorium, and Megalomyrmex 158). More than 20 such compounds have been identified in myrmicine ants 134,149,158-161). These include the /rans-pyrrolidine 197B. Incidentally, all ant pyrrolidines so far detected are of the trans configuration. A trans-2-n-butyl-5-n-heptylpyrrolidine (cf. 225C) occurs in ants, but a 2,5-di-/i-butylpyrrolidine (cf. 183B) has not been reported. 

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. 

Acylic syn-1,4-chloroacetates were used in a similar sulfonamide substitution-cyclization reaction for their transforaiation to stereodefined 2,5-disubstituted pyrrolidines (Scheme 8-24] [83]. Some of these 2,5-disiibstitiited pyrrolidines are ant venom pheromones and are also found in the skin of frogs. 

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