Studies on the Syntheses of Multilayered [2. 2] Paracyclophanes

It is well-known that a number of double-layered compounds such as [2. 2]paracyclophane show anomalous physical and chemical properties due to the transannular π-electronic interaction between the stacked aromatic rings.²) Moreover, the interaction significantly increases with an increase of the layers as observed in a series of multilayered [2. 2]paracyclophanes³) and thereby it is of great interest to search a possibility of an organic semiconductor or its suitable model in them or their derivatives. However, such a study has been severely limited by great difficulty on the syntheses of the layered cyclophanes. While a number of synthetic methods have been developed for cyclophanes,²) only 1,6-Hofmann elimination method has so far been adopted to the preparation of multilayered [2.2]paracyclophanes.³) In practice, however, the yield is very low and becomes markedly poor with the increasing layers. Now we have studied some practical improvements on the preparation of multilayered [2.2]paracyclophanes.     

Synthetic study of kosinostatin aglycone: synthesis of BCDE rings using alkoxycarbonylmethylation of diazonaphthoquinone

A synthetic study of kosinostatin aglycone is reported. Synthesis of key intermediate lactone 3, which corresponds to the BCDE ring fragment, was accomplished, and the precursor BCD ring fragment 5 was synthesized via two routes. First, 5 was synthesized from 2,5-dimethoxybenzaldehyde 16 by the combination of typical known transformations including efficient application of non-aqueous OsO₄ oxidation in the presence of PhB(OH)₂. However the synthesis required 15 long steps, and its main difficulty was ortho-alkoxycarbonylmethylation of 1-naphthol. Next we attempted to apply our recently developed alkoxycarbonylmethylation of diazonaphthoquinone for the synthesis of 5, and 5 was successfully synthesized in 9 steps from the same starting compound 16. Finally, 5 was stereoselectively converted to lactone 3 via trifluoroacetic acid-mediated cyclization of the 3,4-epoxycylohexanecarboxylic acid derivative.     

Indole alkaloids from Kopsia jasminiflora

Seven new indole alkaloids (aspidofractinine type 1–3, kopsine type 5, strychnos type 6, and vincamine type 7, 8) were isolated from Kopsia jasminiflora (Apocynaceae) collected in Thailand. 5-Oxokopsinic acid (4) was isolated from nature for the first time. The structures of the new alkaloids were determined by spectroscopic analyses and chemical transformation of a known alkaloid. 5,6-Secokopsinine (1) possesses a dialdehyde function that is formed by oxidative cleavage of the C-5–C-6 bond of kopsinine (9). New vincamine-type alkaloid 8 showed potent inhibitory activity toward human cancer cell lines (A549, HT29, HCT116).     

Identification of novel EED-EZH2 PPI inhibitors using an in silico fragment mapping method

Journal of Computer-Aided Molecular Design - Enhancer of zeste homolog 2 (EZH2) is a histone lysine methyltransferase that is overexpressed in many cancers. Numerous EZH2 inhibitors have been...     

Direct Asymmetric Mannich‐Type Reaction of α‐Isocyanoacetates with Ketimines using Cinchona Alkaloid/Copper(II) Catalysts

The enantioselective direct Mannich‐type reaction of ketimines with α‐isocyanoacetates has been developed. Excellent yields and enantioselectivity were observed for the reaction of various ketimines and α‐isocyanoacetates using cinchona alkaloid/Cu(OTf)₂ and a base. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. This process offers an efficient route for the synthesis of α,β‐diamino acids.     

Fast multipole method for three-dimensional systems with periodic boundary condition in two directions

We derived a new expression for the electrostatic interaction of three-dimensional charge-neutral systems with two-dimensional periodic boundary conditions (slab geometry) using a fast multipole method (FMM). Contributions from all the image cells are expressed as a sum of real and reciprocal space terms, and a self-interaction term. The reciprocal space contribution consists of two parts: zero and nonzero terms of the absolute value of the reciprocal lattice vector. To test the new expressions, electrostatic interactions were calculated for a randomly placed charge distribution in a cubic box and liquid water produced by molecular dynamics calculation. The accuracy could be controlled by the degree of expansion of the FMM. In the present expression, the computational complexity of the electrostatic interaction of N-particle systems is order N, which is superior to that of the conventional two-dimensional periodic Ewald method for a slab geometry and the particle mesh Ewald method with a large empty space at an interface of the unit cell. © 2020 Wiley Periodicals, Inc.     

New mu-opioid receptor agonists with phenoxyacetic acid moiety

New muq-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, 12-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest agonist potency on the MOR in an isolated guinea-pig ileum preparation, and it also had selectivity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells compared with the same types of delta- and kappa-opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more potent MOR agonist activity than loperamide. Furthermore, compound 8 showed a peripheral analgesic activity in vivo screening on rat.     

Detection of multiple anions by thin-layer chromatography

A novel detection method for 21 different anions by thin-layer chromatography is presented. Anions on the target plate form salts with amine in a developing solvent and are visualized after staining with citric acid-acetic anhydride reagent as white spots contrasting against a pale red-pink background. This method has particularly high sensitivity for anions of chlorate, sulfate, phosphate, chromate and dichromate (0.02-0.05 microg). The method is demonstrated to efficiently detect toxic arsenite in curry sauce as an example application. The proposed method offers highly efficient indirect detection for a wide range of anions, and serves as a purification procedure for the preparation of anionic sample solutions for other analytical methods.     

Hydrothermal Synthesis of the Blue Potassium Molybdenum Bronze, K0.28MoO3

Blue potassium molybdenum bronze, K_0.28MoO₃, was prepared by hydrothermal heating hydrogen molybdenum bronze in KCl solution at 431 K. Hydrated molybdenum bronze was found formed as an intermediate during the conversion from hydrogen molybdenum bronze to blue bronze. The hydrothermal method proved itself an easy and effective for synthesis of mixed-valence compounds.     

Oligo(octithienylene-diethynylene)s as unprecedentedly long conjugated nanomolecules

[reaction: see text] A series of oligo(octithienylene-diethynylene)s alternately composed of octithiophene and diacetylene units have been prepared by a random Eglinton coupling reaction among mono- and diethynyloctithiophenes. The largest compound isolated in the oligomeric series is comprised of twelve octithiophene units and eleven diacetylene units, and its molecular length reaches ca. 43 nm, which is the longest among single-component conjugated nanomolecules.