Lepidopteran syntheses

Organocatalytic transfer hydrogenation of enals has been discussed as a route for synthesis of some lepidopteran pheromones. 

After the first three molecular characterizations of animal desaturases from rat liver (Thiede et al., 1986), mouse adipose tissue (Ntambi et al., 1988) and carp (Tiku et al., 1996), a Drosophila desaturase was isolated in 1997 (Wicker-Thomas et al., 1997). Since then, numerous studies have been made on lepidopteran desaturases involved in nonhydrocarbon short-chain pheromones (Knipple et al., 1998 reviewed in Knipple and Roelofs, 2003). In Drosophila, there are seven fatty acyl-CoA desaturase genes, which are all located on chromosome III (Figure 4.1), but only three desaturases appear to be involved in hydrocarbon synthesis. In the cricket, a desaturase has been characterized but there is no evidence that this desaturase is involved in pheromone biosynthesis (Riddervold et al., 2002). On the other hand, the desaturase isolated from the housefly is probably involved in both lipid and pheromone biosynthesis (Eigenheer et al., 2002). 

The isolation of the desaturase gene olel from the yeast (Stukey et al., 1989) and its replacement by the rat desaturase in an olel -mutant yeast which resulted in functional complementation (Stukey et al., 1990) have permitted the functional characterization of insect desaturases. While lepidopteran desaturases with unusual activities have been described (e.g. A10, All, A14) (Knipple et al., 1998 reviewed in Roelofs et al., 2002), the three insect genes functionally characterized to date that are involved in hydrocarbon synthesis correspond to desaturases with a A9 specificity (Dallerac et al., 2000 Eigenheer et al., 2002). However, in some species, desaturases with other specificities that are involved in hydrocarbon synthesis seem likely to occur. 

In the melanogaster subgroup, the same enzyme Desatl seems to be involved in the first desaturation step of pheromone synthesis (Figure 4.7), even if the specificity concerning the desaturation is somewhat modified (for example, in D. erecta, stearic acid is used for the first desaturation, instead of palmitic acid as in other species). In other Drosophila species, other enzymes could be involved Desat2 in D. ananassae and another yet unknown desaturase in D. virilis. The position of the double bond on carbon 11 in the latter species could indicate either that the desaturase acts on C20 saturated fatty acid, or that it has another unknown specificity, resembling the unusual specificities of some lepidopteran desaturases. 

The goal of this chapter is to provide an overview of the occurrence of Type II polyene pheromones and their derivatives, and their chemistry, including their biosynthesis and synthesis. The older literature in this subject area was reviewed in Millar (2000), and summarized more recently in Ando et al. (2004). Thus, this chapter will provide a comprehensive summary of all known Type II pheromone structures and their occurrence in Tables 1 1, whereas the text will focus more on work over the past ten years. The interested reader is further directed to three useful online databases, two of which focus on lepidopteran pheromones (www.tuat.ac.jp/ antetsu/review/e-List.pdf Ando, 2003 www-pherolist.slu. se/pherolist.php Witzgall et al., 2004) and the third of which covers insect pheromones in general (www.pherobase.com El-Sayed, 2008). 

Second, the decarboxylase enzymes required to produce hydrocarbons apparently are not present in lepidopteran pheromone glands, but these enzymes are present in oenocyte cells where most insect hydrocarbon synthesis takes place (Blomquist et al., 1987). Thus, Lepidoptera that produce Type II pheromones must have a mechanism for transport of hydrocarbon pheromone components from the oenocytes to the pheromone gland, where... 

Soulie, J., Ta, C. and Lallemand, J.-Y. (1992). Access to unsaturated chiral epoxides. I. Bisallylic chiral epoxides. Application to the synthesis of lepidopteran pheromones. Tetrahedron, 48,443 452. 

Abstract. The current scope and limitations of organocatalytic reactions and the consequences for the strategic planning of natural product syntheses are discussed. Examples from our group include the total synthesis of UCS1025A and lepidopteran sex pheromones. 

Our strategy can be easily extended to the synthesis of other lepidopteran pheromones just by altering the chain length of starting aide-... 

We have developed a straightforward strategy for the synthesis of an important class of lepidopteran sex pheromones starting from simple dialdehydes. The combination of a Wittig reaction and an organocatalytic reduction represents a useful sequence for the nontrivial two-carbon homologation of aldehydes. 

Fig. (5). Lepidopteran pheromone biosynthetic pathways utilize fatty acid synthesis, desatiindiun, specific chain-shortening enzymes, and/or functional modification of tlie carbony l carbon to produce species-apecific acetate ester, aldehyde, alcohol, or hydrocarbon pheromone blends. Unsaturated hydrocarbons can be further modified to epoxides (adapted from ref. [21]).

An early representative to the benzoylphenyl ureas includes difiubenzuron, discovered by Philips-Duphar B.V. as an inhibitor of chitin synthesis, and commercialized in 1977 for control of lepidopteran and coleopteran pests in fruit, cotton. 

Azadirachtin, applied topically to final-instar larvae of lepidopteran insects, affects oogenesis and reproductive maturation in subsequent female moths (74). Moths obtained from such treated larvae developed fewer mature oocytes, possibly as a result of interference of azadirachtin with vitellogenin synthesis and/or its uptake by developing oocytes. Larval treatments also cause decreased viability of emerging larvae from affected eggs. 

I. van Die, A. van Tetering, H. Bakker, D.H. Van den Eijnden and D.H. Joziasse, Glyco-sylation in lepidopteran insect cells—Identification of a pi 4-lV-acetyIgalactosaminyltransfer-ase involved in the synthesis of complex-type oligosaccharide chains. Glycobiology, 1996, 6, 157-164. 

Van Die, I., Van Tetering, A., Bakker, H., Van den Eijnden, D. H., Joziasse, D. H. Glyco-sylation in lepidopteran insect cells identification of a beta 1-4-acetylgalactosaminyltransferase involved in the synthesis of complex-type oligosaccharide chains. Glycohiology, 1996,6,157-164. 

The capability of dialkylammonium salts to react with a,p-unsaturated aldehydes generating an iminium ion particularly activated towards 1,4-additions was exploited to realize a highly selective conjugate reduction of enals [26]. The optimized conditions for this reaction envision the use of 5 mol% dibenzylanunonium trifluoroace-tate 5a in combination with Hantzsch ester 4a, to yield reduced aldehydes with short reaction times in the case of electron-deficient substrates. The intrinsic regi-oselectivity of this approach found application in the synthesis of various lepidopteran sex pheromones [27] (Scheme 2.3). 

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