Beetles, trees, mice and antelopes

Bark beetles have sophisticated chemical signalling systems which control tree colonisation within ⁴ and between species ⁵. exo-Brevicomin 1 is a male attractant produced by female western pine beetles, Dendroctonus brevicomis. It was the first of a series of bark beetles pheromones ⁶ with the 6,8-dioxa-bicyclo[3.2.1]octane motif ⁷, which includes endo-brevicomin 2 ⁸, frontalin 3 ⁹ and multistriatin 4 ¹⁰. A similar (ring homologous) spiroacetal 5 is produced by Norway spruce in response to attack by the ambrosia beetle, Typodendron lineatum ¹¹ and the unsaturated analogues 6, 7 are male released attractants of the swift moth, Hepialus hecta ^{12 13}. The odour of mouse urine plays an important role in regulating the reproductive status of mice. For example groups of female mice isolated from males lose their estrous cycle (Lee-Boot effect), but this can be restored by dosing their bedding with male urine (cf. Whitten effect) ¹⁴. When young female mice are housed together away from adults, puberty is delayed. Again normal development can be restored by the application of adult urine to their bedding. Mice live in highly structured social groups, in which hierarchical position is determined by aggressive displays between males. During these displays they discharge unusually pungent urine ¹⁵. The levels of dehydo-exo-brevicomin 8, p-toluidine, sec-butyl 9 and iso-butylthiazolines 10 found in adult male mouse urine are reduced in castrates, but only dehydro-exo-brevicomin (8) and p-toluidine levels are restored by treatment with testosterone ¹⁶. A mixture of dehydro-exo-brevicomin (8) and the sec-butylthiazoline (9) spiked into the urine of castrated mice elicits intermale aggression ¹⁷, female attraction, estrous acceleration and synchronisation ¹⁸. Either compound alone in castrate urine or the mixture in water has no effect, indicating that synergists in the urine are essential for full activity. This bioassay work was performed with racemic dehydro-exo-brevicomin ¹⁹, however recently it has been shown that the biological activity resides in the enantiomer 8 depicted ²⁰.

The chirality of the sec-butylthiazoline (9) does not affect biological activity probably because it racemises quickly in solution. It does not seem to play a role elsewhere in nature, but the iso-butylthiazoline (10) and the corresponding thiazole are components of the preorbital gland secretion of two African antelopes, the grey duiker Sylvicapra grimmia and the red duiker Cephalophus natalensis. The secretion is used for marking territory and more of the thiazoline (10) is produced by males which have more closely defined territories than females ²¹. So in this case three mammals and several bark beetles have overlapping complements of two closely related families of compounds which are used for similar purposes.