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The first synthesis of N -(acyloxy)ynamides was realized through the coupling of N -(acyloxy)amides and hypervalent alkynyliodane under mild conditions. This reaction probably involves biradical species ("C 2 ") generation and radical processes. Furthermore, we also demonstrated that N -(acyloxy)ynamide could be transformed into a N -sulfonylimidate derivative by a copper catalyst. This study provides new building blocks for synthetic organic chemistry reactions and improves understanding of the chemical reactivity of "C 2 ".

The reaction of 14-aminonaltrexone with acetic anhydride was found to produce a range of different novel compounds between the free compound and its hydrochloride. The hydrochloride produced a compound with an acetylacetone moiety, whereas the free form produced a compound with a pyranopyridine moiety. Efforts to isolate reaction intermediates and density functional theory calculations have elucidated those formation mechanisms with both bearing the novel morphinan-type skeleton. Furthermore, a derivative with the acetylacetone moiety showed binding to opioid receptors.

Sulfides and their derivatives are among the most important class of reagent in synthetic chemistry. Despite the importance of such compounds, the use of sulfide radical cations in synthetic chemistry is underdeveloped. To address this issue, herein, we describe alkene chlorotrifluoromethylation reactions promoted by photoredox/sulfide dual catalysis systems, which involves sulfide radical cations generated through the oxidation of sulfides by a photoredox catalyst. The high functional group tolerance of this chemistry was demonstrated using natural products and drug molecules as substrate alkenes.

One of the most important questions in evolutionary biology is how the spatial distribution of species is limited. Asymmetric gene flow from core populations is suggested to increase the number of poorly adapted immigrants in the populations at the range edge. Genetic load due to migration, i.e., migration load, should prevent adaptation to the local habitat, leading to decreases in distribution range via local extinction or the limiting range expansion. However, few experimental studies have examined the effects of immigration on fitness and natural selection within recipient populations. To investigate the influence of migration load on the evolution of distribution range, we performed field and laboratory observations as well as population transcriptomics for the common river snail, Semisulcospira reiniana. This species meets the conditions that migration from source populations can prevent local adaptation in a sink population because they inhabit the broader range of environments, including middle/upper reaches of a river and estuaries within a single river and they may be more vulnerable to being swept away by water currents due to lowered spontaneous (upward) locomotion activity. We found that river steepness was related to the lower distribution limit of S. reiniana, with a narrower distribution range in the steeper river. Population transcriptomic analysis showed that gene flow was heavily asymmetric from the upstream populations to downstream ones in the steep river, suggesting a greater migration load in the steep river. The number of genes putatively involved in adaptation to the local habitat was lower in the steep river than in the gentle river. Gene expression profiles suggested that individuals achieve better local adaptation in the gentle river. Laboratory experiments suggested that evolutionary differences in salinity tolerance among local populations were only found in the gentle river. Our results consistent with the hypothesis that migration load owing to asymmetric gene flow disturbs local adaptation and restricts the distribution range of river snails., (© 2022. The Author(s).)

Morphinan derivatives lacking the 4,5-epoxy ring were synthesized to examine the participation of the 14-OH group, the 3-OMe group, and the aromaticity of the A-ring in the activity and selectivity for the orexin 1 receptor (OX 1 R). The assay results and the conformational analyses of the 14-dehydrated and 14-H derivatives suggested that the orientations of the 6-amide side chain and the 17-benzenesulfonyl group would play important roles in the activity for OX 1 R. In the 6β-derivatives, removal of the 3-OMe group and the reduction of the A-ring significantly decreased the activity toward the OX 1 R, but these changes did not affect the 6α-derivatives. These results indicate that the 3-OMe group and the A-ring would be essential structural moieties for the 6β-derivatives., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The 14-dehydration- and 14-H derivatives of the orexin 1 receptor (OX 1 R) antagonist YNT-707 (2) were synthesized. The obtained derivatives showed higher affinities for OX 1 R than the corresponding 14-hydroxy derivatives. The conformational analysis suggested that the 17-sulfonamide groups in the derivatives without the 14-hydroxy group have a greater tendency to be oriented toward the upper side of the D-ring compared with the 14-hydroxy derivatives. Additionally, the 14-dehydration-derivative with 6α-amide side chain showed significantly higher affinity than the 14-hydroxy derivative, while the corresponding 14-H derivative showed only slightly higher affinity. Thus, the 14-hydroxy group strongly affects the affinity of the antagonist for the OX 1 R., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The essential structure of the orexin 1 receptor (OX 1 R) antagonist YNT-707 (2) was clarified, particularly the roles to OX 1 R antagonist activities of the 3-OMe, the 4,5-epoxy ring, the 14-hydroxy group, and the orientation of the 6-amide side chain. The 3-OMe and 17-sulfonamide group were shown to be essential for the OX 1 R antagonistic activity. The 4,5-epoxy ring plays an important role for the active orientation of the 6-amide group. The 14-hydroxy group could lower the activity of the 6β-amide isomer by the interaction of the 14-hydroxy group with the 6-amide group, which could orient the 6-amide group toward the upper side of the C-ring. Finally, we proposed the difference in the active conformation between OX 1 R and κ opioid receptor (KOR), especially in the orientation of the 6-amide group which is expected to be a useful guide for medicinal chemists to design OX 1 R ligands., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Nalfurafine, a κ-selective opioid receptor agonist, unexpectedly showed a selective antagonist activity toward the orexin 1 receptor (OX 1 R) (K i = 250 nM). Modification of the 17-amino side chain of the opioid ligand to an arylsulfonyl group and the 6-furan acrylamide chain to 2-pyridyl acrylamide led to compound 71 with improvement of the antagonist activity (OX 1 R, K i = 1.36 nM; OX 2 R, not active) without any detectable affinity for the opioid receptor. The dihydrosulfate salt of 71, freely soluble in water, attenuated the physical dependence of morphine. Furthermore, all of the active nalfurafine derivatives in this study had almost no activity for OX 2 R, which led to high OX 1 R selectivity. These results suggest that nalfurafine derivatives could be a useful series of lead compounds to develop highly selective OX 1 R antagonists.

A selective and sensitive method for the determination of low molecular weight aliphatic primary amines in urine is described. These amines were converted into their benzenesulphonyl derivatives by a modified Hinsberg procedure, and measured by gas chromatography with flame photometric detection (FPD-GC) using a DB-1 capillary column. The derivatives were very stable and provided excellent FPD responses. By FPD-GC, linear calibration curves were obtained in the range 10-200 ng of methylamine, ethylamine, n-propylamine, isobutylamine and n-butylamine using tert-butylamine as an internal standard, and the detection limits of these amines were ca. 6-25 pg as the injection amount. Benzenesulphonamide derived from ammonia was converted into its N-dimethylaminomethylene derivative which has a longer retention time, and separated from benzenesulphonyl derivatives of low molecular weight primary amines on the chromatogram. The recoveries of aliphatic primary amines added to urine samples were 91-107% and the relative standard deviations were 0.2-4.5%. Analytical results of aliphatic primary amine contents in urine samples of normal subjects are presented.

A selective and sensitive method for the determination of urinary beta-phenylethylamine (PEA) by gas chromatography (GC) has been developed. After extraction of the urine sample with n-pentane, PEA was converted into its N-benzenesulphonamide derivative and then determined by GC with flame photometric detection using a DB-1301 capillary column. By using this method, nanogram amounts of PEA in urine could be accurately and precisely determined without any influence from coexisting substances. Analytical results for the determination of PEA in urine samples from normal subjects are presented.