Solenopsin is alipophilicalkaloid with the molecular formula C17H35N found in the venom offire ants (Solenopsis). It is considered the primary toxin in the venom[2] and may be the component responsible for thecardiorespiratory failure in people who experience excessive fire ant stings.[3]
Structurally solenopsins are apiperidine ring with amethyl group substitution at position 2 and a longhydrophobic chain at position 6. They are typically oily at room temperature, water-insoluble, and present anabsorbance peak at 232 nanometers.[4] Fire ant venom contains other chemically related piperidines which make purification of solenopsin from ants difficult.[5][6] Therefore, solenopsin and related compounds have been the target oforganic synthesis from which pure compounds can be produced for individual study. Originally synthesized in 1993,[7] several groups have designed novel and creative methods of synthesizingenantiopure solenopsin and other alkaloidal components ofant venom.
Thetotal synthesis of solenopsin has been described by several methods.[8][failed verification] A proposed method of synthesis[9](Figure 1) starts with alkylation of 4-chloropyridine with aGrignard reagent derived from 1-bromoundecane, followed by reaction with phenyl chloroformate to form 4-chloro-1-(phenoxycarbonyl)-2-n-undecyl-1,2-dihydropyridine. The phenylcarbamate is converted to theBOC protecting group, and then pyridine is methylated at the 6 position. The pyridine ring is then reduced to a tetrahydropyridine via catalytichydrogenation withPd/C and then further reduced withsodium cyanoborohydride to a piperidine ring. The BOC group is finally removed to yield solenopsin. A number ofanalogs have been synthesized using modifications of this procedure.
A shorter method of synthesis stemming from commercially availablelutidine has been more recently proposed.[10]
Solenopsins are described as toxic against vertebrates and invertebrates. For example, the compound known as isosolenopsin A has been demonstrated to have stronginsecticidal effects[11] which may play a central role in the biology offire ants.
In addition to its toxicity, solenopsis has a number of other biological activities. It inhibitsangiogenesisin vitro via thephosphoinositide 3-kinase (PI3K) signaling pathway,[9] inhibits neuronalnitric oxide synthase (nNOS) in a manner that appears to be non-competitive withL-arginine,[12] and inhibitsquorum-sensing signaling in some bacteria.[13] The biological activities of solenopsins have led researchers to propose a number of biotechnological and biomedical applications for these compounds. For instance, mentioned anti-bacterial and interference in quorum-sensing signalling apparently provide solenopsins with considerable anti-biofilm activity, which suggests the potential of analogs as new disinfectants and surface-conditioning agents.[14] Also, solenopsins have been demonstrated to inhibit cell division and viability ofTrypanosoma cruzi, the cause ofChagas disease, which suggests these alkaloids as potential chemotherapeutic drugs.[15]
Solenopsin and analogs share structural and biological properties with thesphingolipidceramide, a major endogenous regulator ofcell signaling, inducingmitophagy and anti-proliferative effects in different tumor cell lines.[16]
Syntheticanalogs of solenopsin are being studied for the potential treatment ofpsoriasis.[17]
^Stereochemistry per:Leclercq S, Thirionet I, Broeders F, Daloze D, Vander Meer R, Braekman J (1994). "Absolute configuration of the solenopsins, venom alkaloids of the fire ants".Tetrahedron.50 (28):8465–8478.doi:10.1016/S0040-4020(01)85567-8.
^Pianaro A, Fox EG, Bueno OC, Marsaioli AJ (May 2012). "Rapid configuration analysis of the solenopsins".Tetrahedron: Asymmetry.23 (9):635–642.doi:10.1016/j.tetasy.2012.05.005.
