Drosophila pheromone, synthesis

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. 

One further application is the synthesis of (S)-l-methyldodecyl acetate, the pheromone of Drosophila mulleru by a deprotonation/methylation sequence starting with 1 -dodecanol in 59 % overall yield and very high enantioselectivity (98% ee)43. 

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). 

Can a general pathway be drawn for HC synthesis in Drosophila In mature D. mela-nogaster, only three desaturases seem to participate in pheromone biosynthesis, but as reported in the previous paragraphs, at least four elongases are involved (in cytological positions 55, 68, 85). 

Figure 4.7 Phylogenetic tree of Drosophila, principal pheromones of the species and desaturases involved in their synthesis, (http //flybase.bio.indiana.edu/).

The simple compound 79 is an aggregation pheromone of the fruit fly Drosophila mulleri. Hoppe proposed to synthesise it by asymmetric deprotonation and retentive methylation of a carbamate derivative of n-dodecanol.8 Given that the carbamate group (required for directed oc-lithiation) must, at the end of the synthesis, be removed from the molecule, the best choice is the tetramethyloxazolidine-derived 81, readily formed by acylation with the carbamoyl chloride 80. Lithiation of 81 with excess s-BuLi-(-)-sparteine gives, by asymmetric deprotonation, a configurationally stable complex of organolithium 82 with (-)-sparteine. 

Morita A, Matsuyama S, Oguma Y, Kuwahara S. Simple synthesis of the major sex pheromone components of Drosophila ananassae and D-paUidosa. Biosci. Biotechnol. Biochem. 2005 69(8) 1620-1623. 

An early demonstration, reported by Hoppe, of the use of sparteine for the generation of dipole-stabilized carbanions and their subsequent application in asymmetric synthesis involves carbamates such as 37 (Scheme 13.5) [48], The synthesis of the Drosophila mulleri pheromone (S)-l-methyldodecyl acetate (39) illustrates the features of this process. This approach was also employed with substrate 40 (> 95 % ee), which could be sequentially metalated and functionalized to give 42 (dr >97 3) as shown in Scheme 13.6 [49]. 

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