Epoxide pheromones

A new analytical method [34] for the enantiomeric purity of epoxide pheromones as well as a new method [35] for stereochemical inversion of saturated epoxides were reported by Oliver. 

A study using the gypsy moth, Lymantria dispar, illustrates the overall pathways involved in production of epoxide pheromone components (Fig. 3) [77]. This insect uses disparlure, Me2,epo7-18 H, as a pheromone component. In-... 

Scheme 8 Syntheses of cis-Z- and Jrans-Z-bisabolene epoxide pheromone components from Nezara viridula and other stink bug species, part 1 [67,71,76,77]...

Central to investigations of the biosynthetic pathway and regulation of the contact pheromone of B. germanica was the observation that the major cuticular hydrocarbon in all life stages of this species is an isomeric mixture of 3,7-, 3,9-and 3,11-dimethylnonacosane (Jurenka el al., 1989). The presence of only the 3,11-isomer in the cuticular dimethyl ketone fraction and only in adult females prompted Jurenka et al. (1989) to suggest that production of the pheromone might result from the female-specific oxidation of its hydrocarbon analog. This scheme follows the well-established conversion of hydrocarbons to methyl ketone and epoxide pheromones in the housefly (Blomquist et al., 1984 Ahmad et al., 1987). 

In contrast, the hemolymph of females of the arctiid moth Spilosoma imparilis were found to contain significant levels of the polyunsaturated hydrocarbons corresponding to the epoxide pheromone components produced by this species (Wei el al., 2003). In a biosynthetic study with the arctiid Syntomoides imaon, the pheromone of which consists of a blend of 3Z,6Z,9Z-21 H and 1,3Z,6Z,9Z-21 H (Matsuoka el al., 2008), the lipids extracted from oenocytes and peripheral fat bodies associated with the abdominal integument contained both (llZ,14Z,17Z)-eicosa-ll,14,17-trienoic acid and (13Z,16Z,19Z)-docosa-13,16,19-trienoic acid, the intermediates predicted by elongation of linolenic acid by one or two cycles of 2-carbon chain extension (Ando et al., 2008). The latter acid is likely to be the direct biosynthetic precursor to 3Z,6Z,9Z-21 H (Ando et al., 2008). 

In a parallel study, Wei et al. (2003) showed that the triene precursors to epoxide pheromones were present, along with a variety of other hydrocarbons, in extracts of hemolymph from females of two geometrid (A. selenaria cretacea and II. artilineata) and one arctiid species (Spilosoma imparilis). The epoxides were not found in the hemolymph extracts, nor were the trienes found in extracts of hemolymph from males. When labeled trienes were injected into the abdomens of females, labeled epoxides were later recovered from pheromone glands, demonstrating that the injected compounds had been transported to and taken up by the glands, and that triene hydrocarbons, synthesized somewhere outside the glands (probably in oenocytes), were the direct precursors to the epoxide pheromone components. 

The lipophorin proteins in the hemolymph of A. selenaria cretacea were subsequently identified, and as predicted from results of the previous work, were shown to accept a variety of hydrocarbon substrates (Matsuoka et al., 2006). Labeled 3Z,6Z,9Z-19 H was transported through the hemolymph and selectively delivered to the pheromone gland for epoxidation. Interestingly, lipophorins from hemolymph of both males and females were shown to bind the 3Z,6Z,9Z-19 F1 triene precursor to the epoxide pheromones, even though the triene was not present in males. 

Bell, T. W. and Ciaccio, J.A. (1993). Alkylative epoxide rearrangement. A stereospecific approach to chiral epoxide pheromones../. Org. Chem., 58, 5153-5162. 

Subsequently, a number of new epoxide pheromones were identified, and there was a need to develop a general synthetic method for epoxide pheromones. As shown in Figure 4.29, preparation of enantiomerically pure building block D facilitated the synthesis of (+)-disparlure 85 and other epoxide pheromones. We prepared D by employing lipases.57,58... 

A number of insect pheromones are epoxides. Asymmetric hydrolysis of meso-diacetate 3 (Figure 24.2) witii pig pancreatic lipase (PPL) gives (2S,3P)-4-acetoxy-2, 3-epoxy-l-butanol (4, 90% ee) in 71% yield [4], Various epoxide pheromones were synthesized from (2S,3K)-4, which could be purified to give enantiopure material by recrystallizing tiie corresponding 3,5-dinitrobenzoate. 

In 2003, (2P,3S)-4-f-butyldiphenylsilyloxy-2,3-epoxy-l-butanol (5) with 99.5% ee was prepared and foimd to be a better building block than (2S,3R)-4 (see section "(2R,3S) -t-Butyldiphenylsilyloxy-2,3-Epoxy-l-Butanol (5)") [5]. These two epoxide building blocks 4 and 5 were utilized for the synthesis of not only epoxide pheromones but also pheromone alcohols and ketones after alkylative cleavage of the epoxy ring (Figure 24.3). 

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