Most mammals have two major olfactory subsystems: the main olfactory system (MOS) and vomeronasal system (VNS). It is now widely accepted that the range of pheromones that control social behaviors are processed by both the VNS and the MOS. However, the functional contributions of each subsystem in social behavior remain unclear. To genetically dissociate the MOS and VNS functions, we established two conditional knockout mouse lines that led to either loss-of-function in the entire MOS or in the dorsal MOS. Mice with whole-MOS loss-of-function displayed severe defects in active sniffing and poor survival through the neonatal period. In contrast, when loss-of-function was confined to the dorsal MOB, sniffing behavior, pheromone recognition, and VNS activity were maintained. However, defects in a wide spectrum of social behaviors were observed: attraction to female urine and the accompanying ultrasonic vocalizations, chemoinvestigatory preference, aggression, maternal behaviors, and risk-assessment behaviors in response to an alarm pheromone. Functional dissociation of pheromone detection and pheromonal induction of behaviors showed the anterior olfactory nucleus (AON)-regulated social behaviors downstream from the MOS. Lesion analysis and neural activation mapping showed pheromonal activation in multiple amygdaloid and hypothalamic nuclei, important regions for the expression of social behavior, was dependent on MOS and AON functions. Identification of the MOS-AON-mediated pheromone pathway may provide insights into pheromone signaling in animals that do not possess a functional VNS, including humans.social behavior | pheromone processing | main olfactory system | vomeronasal system M ost mammals have two major olfactory subsystems-the main olfactory system (MOS) and vomeronasal system (VNS). The MOS comprises the main olfactory epithelium (MOE), in which olfactory sensory neurons detect odorants, and their projection target, the main olfactory bulb (MOB) (Fig. S1A). Although the MOS is thought to detect volatile odorants and the VNS is thought to be important for the detection of nonvolatile pheromones, evidence shows that the MOS is also involved in pheromone detection (1-8). Surgical blocking of odorant access to the MOE, but not surgical ablation of the vomeronasal epithelium (VNE), eliminates preference to odors from the opposite sex in ferrets (9, 10). In mice, chemical ablation of the MOE impairs male and female sexual behaviors (11,12). In these experiments in which the MOE was ablated, the function of the VNS is not directly disrupted, because the VNS is activated by direct application of urine to the nostril. Thus, these results indicate that the MOS also contributes to pheromone processing and related behaviors.Nonconditional disruption of genes encoding signal transduction proteins that are required for activation of olfactory neurons, such as cyclic nucleotide-gated channel (Cnga2) or adenylyl cyclase 3, impairs several social behaviors (11,(13)(14)(15). However, complete loss of MOS function causes a...

Nitro groups on alternate corners of cubane enhance the acidity of cubyl hydrogen (pK a ∼21) and provide sufficient activation for ready anion formation. The sodium salt of 1,3,5,7-tetranitrocubane reacts easily with electrophiles and leads thereby to yet more highly substituted cubanes, like carbomethoxy- and (trimethylsilyl)tetranitrocubane. Anions from these species are also easily formed and are useful for further substitution on the cubane nucleus. Dinitrogen tetraoxide reacts with the anion of tetranitrocubane to give 1,2,3,5,7-pentanitrocubane, the first cubane to contain vicinal nitro groups. The reaction probably involves oxidation of the anion to the corresponding radical. Similarly, the anion of pentanitrocubane is used to prepare 1,2,3,4,5,7-hexanitrocubane, the most highly nitrated cubane made to date. Single-crystal X-ray structural information is given for both penta- and hexanitrocubane.

[reaction: see text] A series of [n]paracyclophanediols (n = 8-12) was synthesized by samarium-catalyzed pinacol coupling for their ansa-bridge formation. Enantiomerically pure [n]paracyclophane esters were derived from the diols in a several steps via chiral resolution (for n = 10) or via crystallization-induced asymmetric transformation (for n = 11) by using amino alcohol auxiliaries and their selective cleavages.

Photochemical planar-to-planar chirality transfer was effected by using (R)-[10]paracyclophane-12-carboxylates as a planar-chiral sensitizer and (Z)-cyclooctene and (Z,Z)-1,5-cyclooctadiene as prochiral substrates to give a planar-chiral (E)- and (E,Z)-isomer in up to 44% and 87% enantiomeric excess, respectively, the latter of which being the highest ever reported for a sensitized photochirogenic reaction.