Solenopsin

Structurally solenopsins are a piperidine ring with a methyl group substitution at position 2 and a long hydrophobic chain at position 6. They are typically oily at room temperature, water-insoluble, and present an absorbance peak at 232 nanometers. 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 1993, several groups have designed novel and creative methods of synthesizing enantiopure solenopsin and other alkaloidal components of ant venom.

Total synthesis

The total synthesis of solenopsin has been described by several methods. A proposed method of synthesis(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.

A shorter method of synthesis stemming from commercially-available lutidine has been more recently proposed.