Frontalin, elephant

Rasmussen, L.E.L. and Greenwood, D.R. (2003) Frontalin A chemical message of musth in Asian elephants (Elephas maximus). Chem. Senses 28,433-446. 

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. 

Humans and insects can discriminate enantiomers of the same compound (Friedman and Miller, 1971 Russell and Hills, 1971) (Table 2.1). Blacktailed deer Odocoileus hemionus columhianus) discriminate between the two geometric isomers and somewhat between the enantiomers of the deer lactone (Fig. 2.2) (Brownlee eta/., 1969 Muller-Schwarzeeta/., 1976,1978a). Young male Asian elephants have more (+) than (-) enantiomer of frontalin in their temporal secretion. Their secretion and(+)-frontalin affect conspecifics little. However, the nearly recemic enantiomer mix from mature bulls attracts ovulating females and repels males (Greenwood etal., 2005)... 

Frontalin in the temporal gland secretion of Asian elephants is bound to elephant albumin (Schulte etal, 2005). The bulk of the secretion of the chin gland of the rabbit is protein (Goodrich and Mykytowycz, 1972). 

Figure 5 Chemosensory inspection behaviors by male and female elephants to frontalin (52), demonstrating specific and varying responses to this male pheromone during different life history stages.155...

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... 

Now, let me tell you a story about Asian elephants (Elephas maximus) in connection with frontalin. In 1996, Rasmussen and coworkers found that female Asian elephants use a 97 3 mixture of (Z)- and... 

Examples include the alkylated 2,8-dioxabicyclo[3.2.1]octane (aro-brevicomin, 54), 6,8-dioxabicyclo[3.2.1]-octanes (frontalin, 55, and multistriatin, 56), and the 2,9-dioxabicyclo[3.3.1]nonane (57). Brevicomin, frontalin, and multistriatin are important components of the male or female pheromones of several bark beetle species. More recently, several hydroxylated 6,8-dioxabicyclo[3.2.1]octanes, including 58-60, have been identified from the mountain pine beetle, Dendroctonusponderosae Interestingly, frontalin (55) also represents an important component of the Asian elephant s male pheromone (Figure 20). ... 

Don t suppose that the females always do all the work both male and female olive flies produce pheromones that attract the other sex. The remarkable thing is that one mirror image of the molecule attracts the males while the other attracts the females Mirror image isomers of a molecule called frontalin are also emitted by male elephants female elephants can tell the age and appeal of a potential mate from the amormt of each isomer he produces. 

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. 

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