Ant venom alkaloid

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). 

Ladybird beetles produce a wide variety of polyacetate or fatty acid-derived alkaloids, many of which closely resemble the ant venom alkaloids described in the previous section. The original discovery of coccinelline (75) and precoccinelline (100) (Figure 32) in blood of the European ladybird beetle, C. 1-punctata had been motivated in part by these beetles aposematic coloration and their tendency to reflex-bleed when molested. Many ladybird beetle species share these characteristics and correspondingly are chemically protected by alkaloids as well. The carbon skeletons of almost all of these alkaloids are based on simple unbranched chains. The structures, biology, and laboratory syntheses of ladybird beetle alkaloids have been reviewed previously by Daloze et al and by Glisan King and Meinwald. ... 

The ant venom alkaloids occurring in the genera Solenopsis and Monomorium have been reviewed briefly. The venoms of iMy latinode and M subopacum contain an array of 2,5-dialkylpyrro-lidines (1), and the pyrrolines (2) are also present. All were identified by gas-chromatographic separation followed by mass spectrometry. ... 

A brief review of the chemistry and biology of ant venom alkaloids, some of which are piperidines, has been published, ... 

Hayashi K, Tanimoto H, Zhang H, Morimoto T, Nishiyama Y, Kakiuchi K. Efficient synthesis of alpha, beta-unsaturated alkylimines performed with allyl cations and azides Applications to the synthesis of an ant venom alkaloid. Org Lett 2012 14 (22) 5726-31. 

Recently, a high yielding synthesis of a,p-unsaturated alkyhmines was developed using azides tethered to an allyhc alcohol (i.e., 123) (2012OL5728). Thus, treatment of 123 with p-toluenesulfbnic acid gave rise to unsaturated imines of type 125. A very reasonable pathway to explain this result would involve an initial 1,3-dipolar cycloaddition to give triazoline 124 as a transient intermediate which is easily dehydrated to produce the observed product (Scheme 29). The efficiency of the method was nicely demonstrated by the total synthesis of the Costa Rica ant venom alkaloid 127 from the MOM-masked cycHzation precursor 126. 

The indolizidine alkaloid swainsonine 412, a potential anticancer drug, has been the target of a number of syntheses. Pearson [99] started with 2,3-O-isopro-pylidene-D-erythronolactone 413, which afforded in three steps the allyUc alcohol 414. This compound was in turn submitted to Claisen-Johnson rearrangement and afforded ester 415. Selective dihydroxylation followed by functional group manipulations led to the target alkaloid (Scheme 6.68). An aminyl radical cycHza-tion was the key step in an ant venom alkaloid 416 synthesis [100]. The Claisen-Johnson rearrangement was used in the preparation of both side chains of this pyrroUdine alkaloid (Scheme 6.68). 

Jones TH, Blum MS, Fales HM. Ant venom alkaloids from Solenopsis and Morwrium species recent developments. Tetrahedron 1982 38(13) 1949-1958. 

Fire ant venom alkaloidal natural products (25, 6/()-dihy-dropinidine and (2S,6/ )-isosolenopsins 254 are well known for the inhibition of different bacteria Uke Streptococcus pneumonia. Streptococcus aureus, E. coli, etc. The total synthesis of enantiopure alkaloids was achieved by Hu et al. in four steps starting from the (50-Betti base... 

Yi GB, McClendon D, Desaiah D, Goddard J, Lister A, Mof-fitt J, Vander Meer RK, deSbazo R, Lee KS, Rockhold RW. Fire ant venom alkaloid, isosolenopsin A, a potent and selective inhibitor of neuronal oxidie syntbase. Int. J. Toxicol. 2003 22(2) 81-86. 

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. 

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. 

Ant venoms from the genus Solenopsis have provided an array of 2,6-disubstituted piperidines, including 197-206. A review of the fungicidal, insecticidal and repellent activity of these alkaloids has appeared [476]. Both solenopsin A (198a) and isosolenopsin A (200) were potent inhibitors (Ki = 0.16 pM and 0.24 pM, respectively) of [ HJ-perhydrohistrionicotoxin binding to sites associated with the nicotinic receptor-gated ion channel in the Torpedo califomica electric organ [477]. 

Sharma KR, Fadamiro HY. Fire ant alarm pheromone and venom alkaloids act in concert to attract parasitic phorid flies, Pseudacteon spp. J Insect Physiol 2013 59 (11) 1119-24. 

Wheeler JW, Olubajo O, Storm CB, Duffield RM (1981) Anabaseine venom alkaloid of aphaenogaster ants. Science 211 1051-1052... 

---