3.4- Dehydro-exo-brevicomin

An investigation of the stereochemistry of the urinary substances eliciting intermale aggression in the house mouse established that (l ,7.R)-3,4-dehydro-exo-brevicomin is present in the urine. Due to extremely facile racemization under very mild conditions, it was concluded that 2-sec-butyl-4,5-dihydrothi-azole 2 it is present in the urine as the racemate. It was suggested that the acidity of mouse urine probably promotes racemization of the optically active compound derived biosynthetically from an amino acid [36]. The observation that female house mice prefer the urinary odors of males uninfected by the intestinal nematode Heligmosomoidespolygyrus suggests that urine may also be important in conveying information on the infection status of males [37]. 

Two compounds in the urine of male mice trigger attacks by other males 3,4-dehydro-exo-brevicomin and 2-5CC-butyl-4,5-dihydrothiazole (Novotny etal., 1985b). The behavior of male mice depends on the context in which they encounter these compounds. When smeared on castrates or females, they release aggressive behavior, but applied to pups, they inhibit infanticide. Therefore, it appears to be more appropriate to consider the these as signals of maleness rather than aggression pheromones (Mucignat-Caretta etal., 2004). 

The concentrations of 16 constituents of male mouse urine vary with the male s dominance status. Dihydrofurans, ketones, and acetates decreased in subordinates. Two sesquiterpene compounds, a- and /3-farnesene, are elevated in dominants urine 1 week after establishing dominance. The bladder or voided urine of dominants contains more 2-5ec-butyl-4,5-dihydrothiazole. Four compounds depend on hormones a- and /5-farnesene, dehydro-exo-brevicomin, and 2-5cc -butyl-4,5-dihydrothiazole. The latter two are absent in urine of immature or castrated males, and testosterone treatment restores their presence. In addition, a-and /3-farnesene do not occur in urine of immature males and are merely reduced in urine of castrates. They are not found in bladder urine and originate in the preputial glands (Harvey etal., 1989). While subordinate male mice have reduced levels of farnesenes, levels of their major urinary proteins remain high (Malone etal, 2001). 

The structural similarities between the putative mammalian chemosignals and the pheromones identified previously in the insect world are quite striking. The farnesenes [257, 258] (entries 66, 67) and 2-heptanone [259] (entry 68) have been implicated previously as insect pheromones. There is only one double bond distinguishing the male mouse pheromone 3,4-dehydro-exo-brevicomin (entry 65) from a bark beetle pheromone [260], brevicomin. In addition, the elephant pheromone (Z)-7-dodecen-l-yl acetate (entry 69) is also known to be an insect pheromone [259]. While the potency may not compare to the insect system, investigators are beginning to find evidence that many mammals ranging from pigs to elephants can have a pheromone-type response to a sniff of secretions even humans appear to respond [261],... 

R, 5S,7R) -3,4-Dehydro -exo-brevicomin and (S)-2-sec -butyl-4,5-dihyrothiazole, the pheromone components of the male mouse... 

In 1984, 3,4-dehydro-exo-brevicomin (99, Figure 4.50) and 2-sec -butyl-4,5-dihydrothiazole (100) were isolated by Novotny and coworkers from the urine of the male house mouse (Mus musculus) as pheromone components.92 They act, synergistically, in promoting intermale aggression, sex attraction, and estrus synchronization in female mice. It was later found that the natural components are ( R,5S,lR)-99 and (S)-100. Additional achiral compounds 101 and 102 were also identified as possible pheromone components. 

Figure 4.50 Synthesis of (1 R,5S,7R)-3,4-dehydro-exo-brevicomin and (S)-2-sec-butyl-4,5-dihydrothiazole, the mouse pheromone...

Figure 4. MUP-bound ligands. These molecules have all been identified bound to MUPs. They are the two naturally occurring ligands, 2-sec butyl-4,5 dihydrothiazole and 3,4-dehydro-exo-brevicomin, and menadione, the protein-bound ligand observed in urine posts, used as a competitive displacer for behavioural studies.

Figure 7. The role of MUPs in the slow release of signalling molecules. Urine containing MUPs, complete with natural ligands, were treated with menadione, which acts as a competitive displacer. These urine streaks were then used in behavioural assays that measured the duration of the initial hesitancy to approach the sample, and the duration of investigative behaviour once the hesitation was overcome. Controls demonstrated that the effect of menadione was attributable to the lack of natural signals (Hurst et al., 1998). The ordinate refers to the age of the urine deposit. The control sample contained water in place of urine. In parallel samples, the loss of 2-sec butyl-4,5 dihydrothia-zole (Thiazole) and 3,4-dehydro-exo-brevicomin (Brevicomin) was measured, and is expressed relative to unaged samples.

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