Solenopsin

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Solenopsin
Solenopsin.svg
Names
IUPAC name
(2R,6R)-2-Methyl-6-undecylpiperidine[1]
Other names
Solenopsin A
Identifiers
3D model (JSmol)
ChemSpider
Properties
C17H35N
Molar mass 253.474 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Solenopsin is an alkaloid with the molecular formula C17H35N found in the venom of fire ants (Solenopsis). It is considered the primary toxin in the venom[2] and may be the component responsible for the cardiorespiratory failure in people who experience excessive fire ant stings.[3]

Chemically, solenopsin contains a piperidine ring substituted with a methyl group and a long hydrophobic chain. Fire ant venom contains other chemically related piperidines which make purification of solenopsin from ants difficult. Therefore, solenopsin and related compounds have been the target of organic synthesis from which pure compounds can be produced for individual study. Originally synthesized in 1998, several groups have designed novel and creative methods of synthesizing enantiopure solenopsin and other alkaloidal components of ant venom.

Total synthesis[edit]

The total synthesis of solenopsin has been described by several methods.[4] The method proposed by Bowen et al.[5](Figure 1) starts with alkylation of 4-chloropyridine with a Grignard 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 the BOC protecting group, and then pyridine is methylated at the 6 position. The pyridine ring is then reduced to a tetrahydropyridine via catalytic hydrogenation with Pd/C and then further reduced with sodium cyanoborohydride to a piperidine ring. The BOC group is finally removed to yield solenopsin. A number of analogs have been synthesized using modifications of this procedure.

Figure 1. Example synthesis of racemic solenopsin

Biological activities[edit]

In addition to its toxicity, solenopsis has a number of other biological activities. It inhibits angiogenesis in vitro via the phosphoinositide 3-kinase (PI3K) signaling pathway,[5] inhibits neuronal nitric oxide synthase (nNOS) in a manner that appears to be non-competitive with L-arginine,[6] and inhibits quorum-sensing signaling in some bacteria.[7]

Solenopsin and analogs share structural and biological properties with the sphingolipid ceramide, a major endogenous regulator of cell signaling, inducing mitophagy and anti-proliferative effects in different tumor cell lines.[8]

Synthetic analogs of solenopsin are being studied for the potential treatment of psoriasis.[9]

References[edit]

  1. ^ Stereochemistry per: Leclercq, S.; Thirionet, I.; Broeders, F.; Daloze, D.; Vander Meer, R.; Braekman, J.C. (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.
  2. ^ Touchard, A; Aili, S. R; Fox, E. G; Escoubas, P; Orivel, J; Nicholson, G. M; Dejean, A (2016). "The Biochemical Toxin Arsenal from Ant Venoms". Toxins. 8 (1): 30. doi:10.3390/toxins8010030. PMC 4728552. PMID 26805882.
  3. ^ Howell G, Butler J, Deshazo RD, Farley JM, Liu HL, Nanayakkara NP, Yates A, Yi GB, Rockhold RW (2005). "Cardiodepressant and neurologic actions of Solenopsis invicta (imported fire ant) venom alkaloids". Ann Allergy Asthma Immunol. 94 (3): 380–6. doi:10.1016/S1081-1206(10)60991-X. PMID 15801250.
  4. ^ Leclercq, S.; Daloze, D.; Braekman, J.-C. (1996). "A Synthesis of the Fire Ant Alkaloids, Solenopsins". Org. Prep. Proced. Int. 28 (5): 499. doi:10.1080/00304949609458571. Archived from the original on 2003-03-20.[not in citation given]
  5. ^ a b Arbiser JL, Kau T, Konar M, Narra K, Ramchandran R, Summers SA, Vlahos CJ, Ye K, Perry BN, Matter W, Fischl A, Cook J, Silver PA, Bain J, Cohen P, Whitmire D, Furness S, Govindarajan B, Bowen JP (2007). "Solenopsin, the alkaloidal component of the fire ant (Solenopsis invicta), is a naturally occurring inhibitor of phosphatidylinositol-3-kinase signaling and angiogenesis". Blood. 109 (2): 560–5. doi:10.1182/blood-2006-06-029934. PMC 1785094. PMID 16990598.
  6. ^ Yi GB, McClendon D, Desaiah D, Goddard J, Lister A, Moffitt J, Meer RK, deShazo R, Lee KS, Rockhold RW (2003). "Fire ant venom alkaloid, isosolenopsin A, a potent and selective inhibitor of neuronal nitric oxide synthase". Int J Toxicol. 22 (2): 81–6. doi:10.1080/10915810305090. PMID 12745988.
  7. ^ Park, Junguk; Kaufmann, Gunnar F; Bowen, J. Phillip; Arbiser, Jack L; Janda, Kim D (2008). "Solenopsin A, a Venom Alkaloid from the Fire Ant Solenopsis invicta,Inhibits Quorum‐Sensing Signaling in Pseudomonas aeruginosa". The Journal of Infectious Diseases. 198 (8): 1198–201. doi:10.1086/591916. PMID 18713055.
  8. ^ Karlsson I, Zhou X, Thomas R, Smith AT, Bonner MY, Bakshi P, Banga AK, Bowen JP, Qabaja G, Ford SL, Ballard MD, Petersen KS, Li X, Chen G, Ogretmen B, Zhang J, Watkins EB, Arnold RS, Arbiser J (2015). "Solenopsin A and analogs exhibit ceramide-like biological activity". Vascular Cell. 7 (5). doi:10.1186/s13221-015-0030-2. PMC 4443652. PMID 26015865.
  9. ^ Arbiser, Jack L; Nowak, Ron; Michaels, Kellie; Skabytska, Yuliya; Biedermann, Tilo; Lewis, Monica J; Bonner, Michael Y; Rao, Shikha; Gilbert, Linda C; Yusuf, Nabiha; Karlsson, Isabella; Fritz, Yi; Ward, Nicole L (2017). "Evidence for biochemical barrier restoration: Topical solenopsin analogs improve inflammation and acanthosis in the KC-Tie2 mouse model of psoriasis". Scientific Reports. 7 (1): 11198. doi:10.1038/s41598-017-10580-y. PMC 5593857. PMID 28894119.

Further reading[edit]