Synthesis of polyzonimine

In this chapter we discussed the synthesis of ten insect-related bioregulators. Mimics of juvenile hormones are now used practically as pesticides. Semiochemicals, some of which were discussed here, are interesting compounds for their future utilization as ecofriendly agents for pest control. 

Mitsui, T. Fukami, J. Ohtaki, T. Agric. Biol. Chem. 1971, 35, 1116-1127. 

Kiguchi, K. Mori, K. Appl. Entomol. Zool. 1971, 6, 218-220. 

Nihmura, M. Aomori, S. Mori, K. Matsui, M.Agric. Biol. Chem. 1972, 36, 889-892. 

2373-2377. 

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Phosphonate esters can be deprotonated with sodium hydride or alkoxide anions to give enolate-type anions that react well with aldehydes or ketones to give -alkenes. Alkene-forming reactions with phosphonates are called Horner-Wadsworth-Emmons (or Horner-Emmons, Wadsworth-Emmons, or even Horner-Wittig) reactions. This example is a reaction that was used by some Japanese chemists in the synthesis of polyzonimine, a natural insect repellent produced by millipedes. 

The first synthesis of polyzonimine (119) was a synthesis of the racemate carried out by Smolanoff and co-workers in 1975 at the time of its isolation and structure elucidation (111). Oxidation of 3,3-dimethylcyclohexene (368) with meto-perchlorobenzoic acid followed by treatment of the epoxide with lithium bromide and HMPA in refluxing benzene gave the carboxal-dehyde 369. The morpholino enamine 370 was then subjected to Michael addition with nitro-ethylene, generated from 2-acetoxy-nitroethane, to afford a nitro aldehyde 37L Ketalization and reduction with Raney nickel then afforded ( )-119 in overall yield for the five steps of 22% (Scheme 45) (111). 

Last but not least, a very intriguing terpenoid pyrrolidine alkaloid, poly-zonimine was milked from the millipede Polyzonium rosalbum (148). The structural formula of polyzonimine (118) is based on an X-ray crystallographic analysis of its perchlorate and by a total synthesis. 

Our synthesis of (5,)-(+)-polyzonimine (69) is summarized in Figure 3.18.52,53 Commercially available 2-methylcyclohexanone A was converted to aldehyde B. This was treated with (S)-prolinol methyl ether... 

In a similar reaction, (,S )-1 was transformed to 5, an intermediate in the synthesis of optically active polyzonimine (a millipede pheromone) via 3 and 4 after sodium borohydride reduction, acetylation and permanganate oxidation. Homogeneous (i J-aldehyde 4 is isolated after purification by GC. Based on the transition state models the absolute configuration of 4 was predicted to have R configuration346. 

Polyzonimine, C10H17N, occurs in the defence secretion of the millipede Polyzonium rosalbum. It is a liquid, monoterpenoid, tertiary base containing an imino nitrogen atom, revealed by spectroscopy [i (C=N) 1626 cm ]. An X-ray diffraction analysis of a perchloric acid derivative revealed structure (4) for the alkaloid, confirmation being provided by synthesis (Scheme 1). Tests on the compound demonstrated its irritancy towards various insects. ... 

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