Polyzonimine: A Novel Terpenoid Insect Repellent Produced by a Milliped

Abstract

A nitrogen-containing terpene 6,6-dimethyl-2-azaspiro[4.4]non-1-ene (polyzonimine) was isolated from the defensive secretion of the milliped Polyzonium rosalbum. Polyzonimine, which is repellent to such natural enemies of the milliped as ants, acts as a topical irritant to insects (10-4 M induces scratching in cockroaches). Its structure was confirmed by a five-step synthesis starting from 2,2-dimethyl-7-oxabicyclo[4.1.0]heptane.

Bioactive alkaloids of frog skin: Combinatorial bioprospecting reveals that pumiliotoxins have an arthropod source

“…The spiropyrrolizidine O-methyloxime 236 had not been detected from an arthropod source but was proposed to be a millipede alkaloid based on having a ring system identical to that of the millipede alkaloid nitropolyzonamine (21), which has a nitro group instead of the Omethyloxime substituent of 236 (22). It was found in three of nine mixed millipede collections (data not shown).…”

Convergent evolution of chemical defense in poison frogs and arthropod prey between Madagascar and the Neotropics

“…By contrast, spirobolid and spirostreptid millipedes that in our study did not yield detectable alkaloids, have chewing mandibles and feed on leaf-litter (65)(66). The SpiroPs provide chemical defense to both the bright red millipede R. purpureus and the poison frogs that sequester these alkaloids: SpiroPs 222, 236, and 238 act as noncompetitive blockers of nicotinic receptors with selectivity for the ganglionic subtype (67), whereas polyzonamine 151B is an effective ant repellent and general topical irritant to other insects (34). Assuming that R. purpureus is a recent arrival to Madagascar, this finding suggests that the sequestration physiology of Mantella may have been already preadapted to accept SpiroP alkaloids.…”

Enantioselective synthesis of (+)-polyzonimine, defensive monoterpene alkaloid produced by a milliped Polyzonium rosalbum, and determination of its S absolute configuration by Its conversion to (4S,5R,6S)-(+)-nitropolyzonamine

“…However, this must be proved. The structures 1 and 2 proposed for these milliped alkaloids were confirmed by the synthesis of their racemates 2,3,5 . Only a single existing asymmetric synthesis of (+)-1 with 68% ee could not tell us anything about its absolute configuration 6 .…”

“…2,5 Commercially available 2-methylcyclohexanone (3) was converted to 4 according to Kawanobe et al 8 . Oxidation of 4 with hydrogen peroxide afforded 5 9 , which was reduced with lithium aluminum hydride to give alcohol 6.…”

“…In 1975, in the course of their studies on compounds from the defensive glands of a milliped Polyzonium rosalbum, Meinwald, Eisner and their respective co-workers isolated and identified the following two nitrogen-containing spirocyclic compounds 2,3 . (+)-Polyzonimine {6,6-dimethyl-2-azaspiro [4.4]non-1-ene (1)} was isolated as a volatile insect repellent, which acts as a topical irritant to predating insects such as ants and cockroaches 2 (Figure 1).…”