Frontalin insect pheromone

Some insect pheromones are internal ketals. We have already mentioned multistriatin (pp T 2 and 99) and frontalin p 193). Brevicomin (22) is another example. Disconnection of the ketal gives (23) containing a 1,2-diol. Among other syntheses, hydroxy-lation of protected enone (24) by epoxidation and acid catalysed rearrangement gives brevicomin stereo-specifically,... 

Abstract A relatively small number of mammalian pheromones has been identified, in contrast to a plethora of known insect pheromones, but two remarkable Asian elephant/insect pheromonal linkages have been elucidated, namely, (Z)-7-dodecen-1-yl acetate and frontalin. In addition, behavioral bioassays have demonstrated the presence of a chemical signal in the urine of female African elephants around the time of ovulation. Our search for possible ovulatory pheromones in the headspace over female African elephant urine has revealed for the first time the presence of a number of known insect pheromones. This search has been facilitated by the use of a powerful new analytical technique, automated solid phase dynamic extraction (SPDE)/GC-MS, as well as by novel macros for enhanced and rapid comparison of multiple mass spectral data files from Agilent ChemStation . This chapter will focus on our methodologies and results, as well as on a comparison of SPDE and the more established techniques of solid phase microextraction (SPME) and stir bar sorptive extraction (SBSE). 

Use of automated headspace SPDE/GC-MS not only enabled the identification in female African elephant urine of a number of known insect pheromones (compounds 2-6, Fig. 2.1), but also revealed the presence of the beetle biochemical precursors to frontalin (2), exo-brevicomin (3) and ent/o-brevicomin (4), thus suggesting a common biosynthetic pathway (Goodwin et al. 2006). Extensive behavioral bioassays must be performed to determine whether any of these compounds is functioning as a pheromone among African elephants. 

It is time to look at some examples. The insect pheromone frontalin can be drawn like this. 

The Sharpless epoxidation has been used to synthesize many chiral natural products, including two insect pheromones—(+)-a-multistriatin and (-)-frontalin, as shown in Figure 12.11. 

Frontalin and multistriatin are two insect pheromones that contain a cyclic acetal. What hydrolysis products are formed when each compound is treated with aqueous acid ... 

Which of these molecules will cycUze to give the insect pheromone frontalin ... 

The western pine beetle Dendroctonus brevicomis is perhaps the most destmctive insect enemy of western pine forests. The aggregation pheromone is a mixture of the terpenoid myrcene [123-35-3J (163) from the tree and the frass pheromones exo-hsevicomki [20290-99-7] (164) and frontalin [28401-39-0] (165). The Norway spmce beede Ips tppopraphus converts the tree terpenoid myrcene into the frass pheromone ipsdienol [33628-00-3] (166) and the beedes also produce 2-methyl-3-buten-2-ol [115-18-4] and rir-verbenol [473-67-6] (167), all of which are components of the aggregation pheromone. 

Fluorinated analogues of (/ )-(—)-sulcatol and of frontalin, which are aggregative pheromones of wood destructive insects have been prepared by means of chiral sulfoxides (Figures 4.40 and 4.41). ... 

Hall G. M., Tittiger C., Blomquist G. J., Andrews G., Mastick G., Barkawi L. A., Bengoa C. S. and Seybold S. J. (2002b) Male Jeffrey Pine Beetles, Dendroctonus jeffreyi, synthesize the pheromone component frontalin in anterior midgut tissue. Insect Biochem. Mol. Biol. 32, 1525-1532. 

Barkawi L. S., Francke W., Blomquist G. J. and Seybold S. J. (2003) Frontalin de novo biosynthesis of an aggregation pheromone component by Dendroctonus spp. bark beetles (Coleoptera Scolytidae). Insect Biochem. Molec. Biol, (in press). 

First identified in Asian elephants during a headspace analysis of volatiles collected from secretions of the musth temporal gland of adult males,156 frontalin (52) is a bicyclic ketal, which is structurally reminiscent of the male mouse priming pheromone component 3,4-dehydro-ara-brevicomin (37). Frontalin (52), Z-7-dodecen-l-yl acetate (51), was already known because of its chemosensory role in the insect world it is an aggregation pheromone in bark beetles.157 Interestingly, the ratio of the two enantiomers of frontalin (52) changes with age and stage of musth and elicits different behavioral responses.158... 

What are some examples of these attractants (Figure 1) For mate finding, the insect-produced pheromones are the primary examples. However, environmental factors may also play an important role in the effectiveness of attractants. In the southern pine beetle, Dendroctonus frontalis. alpha-pinene released from an attacked tree is necessary along with the endogenously produced frontalin in order to attract males for mating (14). 

In some insects, fatty acid elongation followed by decarboxylation produces the hydrocarbon pheromones, and these include examples of lepidopterans (Jurenka), dipterans [71], the German cockroach [72a] (see Fig. 6) and the social insects [73]. More recent work in bark beetles has shown that Ips and Dendroctonus spp. produce their monoterpenoid-derived pheromones ipsenol, ipsdienol and frontalin by modifications of... 

Synthesis of those insect aggregation pheromones having bridged structures may have important economic consequences. Multistriatin (120) is an aggregation pheromone of a European elm bark beetle. A stereoselective synthesis "" has been reported from tartaric acid. A delightfully simple synthesis " of frontalin (121), a pheromone of the pine beetle, is by photolysis of heptane-2,6-dione in methanol-titanium chloride. We also note further photochemical studies... 

Bark beetles. Insects related to the weevils that bore into the wood and bark of trees and often cause extreme economic damage to forests. Many species live in symbiosis with fungi the elm bark beetle Scolytus multistriatus transmits the feared elm tree disease caused by the fungus Ceratocystis ulmi. Some B. species are controlled by the application of synthetic pheromones in trap devices, that contain combinations of pheromones with synthetic insecticides see also bre-vicomin, chalcogran, conophthorin, frontalin, ipsdienol, lineatin, multistriatin, pityol, sulcatol, seudenol. 

Here is an example. The pheromone frontalin is a remarkable compound used by both insects and by elephants to attract a mate. Its structure and H NMR spectrum are shown below. 

Brevicomin (73) and frontalin (74), probable products of fatty acid metabolism, are part of the pheromone system of bark beetles of the genus Dendroctonus. These compounds are involved in interactions of these insects with their host plants, many of which are important softwoods (gymno-sperms) (Fig. 2.30). 

Note (—)-Frontalin is an active component of the aggregating pheromone of pine beetle, which devastates whole pine-tree forests, and is therefore used to kill this insect. Over 30 asymmetric syntheses of (-)-frontalin have been published, which due to their complexity, many steps and low yields remain of academic interest. The synthesis we discuss enabled preparation of 10 g of ( )-frontalin in ten steps with a total yield of 7.8 % [9]. This was the quantity needed for the field studies aimed at controlUng various insect populations. 

---