Nobuhiro Kanomata

Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice

Significance It is now widely accepted that the range of pheromones that control social behaviors are processed by both the vomeronasal system (VNS) and the main olfactory system (MOS). However, the functional contributions of each subsystem in social behavior remain unclear. Here, we showed that mice with loss-of-function confined to the dorsal MOS maintained innate odor recognition and VNS activity, but failed to demonstrate multiple male and female social behaviors. Functional dissociation of the MOS and VNS enabled the identification of an MOS-mediated processing of semiochemical information, independent of the VNS. 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.

Stereocontrol of molecular jump-rope: Crystallization-induced asymmetric transformation of planar-chiral cyclophanes

Abstract Stereocontrol of cyclophane-type planar chirality was achieved by spontaneous dynamic resolution via crystallization-induced asymmetric transformation. Simply heating a 1/1 mixture of the solid and the liquid diastereoisomers of bridged nicotinamides ( S ,3′ S )- 1a – f and ( R ,3′ S )- 2a – f accelerated their rope-skipping isomerization with precipitation of the solid ( S ,3′ S )- 1a – f , completing the disequilibriation to ( S ,3′ S )- 1a – f with up to 99% de.

Planar-to-planar chirality transfer in the excited state. Enantiodifferentiating photoisomerization of cyclooctenes sensitized by planar-chiral paracyclophane.

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.

A simple method removing 2-oxazolidinone and 2-hydroxyethylamine auxiliaries in methoxide-carbonate systems for synthesis of planar-chiral nicotinate

A facile and practical removal of 2-oxazolidinone and 2-hydroxyethylamine auxiliaries was accomplished by treating the corresponding N-acyl-2-oxazolidinone and N-(2-hydroxyethyl)amide derivatives in simple methoxide–carbonate systems. The presence of excess DMC (dimethyl carbonate) accelerates the N-acyl bond cleavage for those substrates under mild reaction conditions, and the present method was found to be useful especially for the synthesis of planar-chiral nicotinate.

Synthesis and structural studies of [n](2,4)pyridinophane ring system☆☆☆

Abstract The facile synthesis of [n](2,4)pyridinophane ring system (n = 9–6) was accomplished by the reaction of N-(1-phenylvinyl)iminophosphorane with cyclic α, β-unsaturated ketones. The chain flipping was studied by 1H NMR spectra at various temperatures.

On the reaction of (vinylimino)phosphoranes and related compounds synthesis and properties of novel 1,6-methanocyclodeca[b]cyclohepta[d]pyrrole

The title compound was synthesized by thermal reaction of 3-phosphoranylidene-amino-1,6-methano[10]annulene with 2-chlorotropone in a single step. The examination of 1H NMR spectrum revealed that there is little contribution of peripheral 18-π electron conjugation, but it is rather composed of 1-azaazulene and methano[10]annulene moieties.

Biomimetic Oxidation of Aldehyde with NAD+ Models: Glycolysis-Type Hydrogen Transfer in an NAD+/NADH Model System

Just like in biological systems, the GAPDH-catalyzed oxidation of aldehyde to carboxylate proceeds in conjunction with 1,4-selective reduction of NAD+ to NADH model compounds [Eq. (1)]. The combination of GAPDH- and LDH-type transfer reactions is also described here as a system mimic for the NAD+ /NADH redox cycle in anaerobic glycolysis. GAPDH=D-glyceraldehyde-3-phosphate dehydrogenase, LDH=L-lactate dehydrogenase.

Adsorption-induced asymmetric transformation of planar-chiral pyridinophanes

Stereocontrol of cyclophane-type planar chirality was investigated via adsorption-induced asymmetric transformation (AIAT) on a series of inorganic porous adsorbents. The rope-skipping equilibria between bridged nicotinamides (S,3′S)-1 and (R,3′S)-2 shifted preferentially to (R,3′S)-2 to accumulate (R)-configuration of planar chirality with up to 61% de (ca. 4/1 ratio) on alumina. The results are in good contrast to accumulation of the corresponding (S)-configuration via conventional crystallization-induced asymmetric transformation (CIAT) to the solid (S,3′S)-1a–d.

Synthesis and structural revision of phomopsin B, a novel polyketide carrying a 10-membered cyclic-ether ring.

Total synthesis of the proposed structure 2 for phomopsin B was achieved by using an intramolecular olefin metathesis as a key step. The spectral data, however, did not match with those of the natural product reported. Re-examination of the reported NMR data led to the structural revision of phomopsin B to known dothiorelone A 18. The R configuration of dothiorelone A was determined by total synthesis through a cross-metathesis with a chiral olefin 19.

The reactions of N-vinyliminophosphoranes. Part 14. A short new synthesis of [n](2,4)pyridinophane ring system (n= 9–6): static and dynamic structural studies of [7]- and [6](2,4)pyridinophanes

A short new synthesis of the [n](2,4)pyridinophane ring system (n= 9–6) consists of allowing N-vinyl- and N-(1-phenylvinyl)iminophosphoranes to react with cyclic α,β-unsaturated ketones. Structural studies of the compounds prepared were based on spectroscopic measurements and MNDO calculations. The 1H and 13C NMR spectra at various temperatures showed dynamic behaviour for the oligomethylene chains of [7]- and [6]-(2,4)pyridinophane derivatives (8c,d). The energy barriers ΔGc‡ of the bridge flipping are 12–13 kcal mol–1(Tc, 20 °C) for (8c) and 21–22 kcal mol–1 kcal mol–1(Tc, 150° C) for (8d). The lower-energy process of the oligomethylene chain in (8d) is the pseudorotation with Ea= 10.3 ± 0.2 kcal mol–1, ΔH‡= 9.8 ± 0.2 kcal mol–1, and ΔS‡=–4.8 cal mol–1 deg–1. Two stable conformations of the hexamethylene bridge of (8d) were unambiguously determined by low-temperature NMR. The strain of the [n](2,4)pyridinophane ring system was found to increase as the chain length becomes shorter. Remarkable deformation of the pyridine rings of (8c,d) was suggested by the geometrical optimization by MNDO calculation and the red shift of the UV spectrum.