Yuji Matsuya

Organic synthesis frequently utilizes acetals as protecting groups for carbonyl functionality during multistep procedures. However, traditional acetal deprotection requires arduous neutralization and purification stages before the carbonyl groups can undergo further functionalization. Therefore, the direct functionalization of acetals remains highly desirable. A one-pot olefination of acetals that eliminates the need for intermediate workup processes during deprotection was developed in this study. A 1,3,5-trioxane-coordinated lithium perchlorate complex ([Li]ClO₄) facilitated both the electrodeprotection and the subsequent Horner-Wadsworth-Emmons reaction. This sequential transformation yielded α,β-unsaturated carbonyl compounds featuring a diverse array of substituent groups. Moreover, these olefination products remained viable for subsequent Michael addition reactions within the same one-pot framework.

We report a design strategy for developing small panchromatic molecules through structural tautomerism. Bridged rhodamine (1) is soluble in water and exhibits excellent light absorption, its molar absorption coefficient exceeding 5000 across the entire UV-visible region from 300 to 750 nm in DMSO. DFT calculations suggest that the barrierless interconversion of the energetically equivalent C10-hydroxy (1a) and C10-carbonyl (1b) forms of 1 contributes to the broadening of the absorption spectrum.

Ligation reactions that proceed at room temperature under aqueous conditions and without catalysts are in high demand, including bioorthogonal reactions. We report a mild amide-ligation reaction of iminophosphoranes with gem-difluoroalkenes. Through experimental and theoretical analyses of intermolecular and intramolecular amidation reactions, we found that the Staudinger-Bertozzi ligation-type reaction of iminophosphoranes with gem-difluoroalkenes is an excellent reaction that proceeds rapidly at room temperature in an aqueous solvent.

The development of bioorthogonal reactions is expected to propel further advances in chemical biology. In this study, we demonstrate Staudinger-Diels-Alder (SDA) ligation as a candidate for a new bioorthogonal reaction. This reaction ligates two molecules via strong C-C bonds at room temperature. We found that the aryl substituent of azide-benzocyclobutene (azide-BCB) had a strong influence on the molecule's tolerance to water. In particular, Cl-substituted azide-BCBs generated the ligated product in high yield, even in the presence of water. Mechanistic investigations using DFT methods revealed that hydrophobic electron-withdrawing substituents suppressed the side reactions of SDA ligation.

Herein, we propose a concept called nonpolar selective emission (NPSE). We demonstrated that NPSE can be used as a sensing mechanism for the detection of chemical gases, and discovered the potential of NPSE dyes as a time-dependent security ink.

An organocatalyzed Fischer indolization is established by combining 2,2′-biphenol (10 mol%) and B(OH)₃ (30 mol%) as weak, readily available, and easy-to-handle acids. The inclusion of MgSO₄, which efficiently scavenges NH₃ (a possible acid catalyst poison), appears to be key to the success of this process. The corresponding indoles are obtained in yields of up to 91% using this method.y Received: 15 February 2024 Accepted after revision: 03 May 2024 Article published online: 17 May 2024 © 2024. Thieme. All rights reserved Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

The recent expansion of photoredox catalysis into chemical biology has underscored the importance of photochemistry, attracting the attention of many researchers. On the other hand, as conventional photoredox catalysts were developed for organic synthesis, there is a necessity to develop biocompatible photoredox catalysts. Here, we show a water-soluble and water-compatible near-infrared (NIR) photoredox catalyst, coerulein B (CB). CB is a water-soluble molecule with a slightly twisted molecular structure, and its anionic species (CB⁻) exhibits NIR absorption and emission. We demonstrated that CB works as a water-compatible photoredox catalyst in the coupling reaction of pyridine hydrochloride and aryldiazonium salt. These results indicate that CB is one of the promising candidates for photocatalysts used in biological reactions.

The one-pot de novo synthesis of pentasubstituted pyridines was realized following the process of Au(I)-autotandem catalysis and subsequent aromatization. The process involves aza-enyne metathesis with aryl propiolates to yield 1-azabutadienes and their addition/6π-electrocyclization sequence with the other propiolate units. The resultant 1,4-dihydropyridines were aromatized to furnish the pyridines in the presence of atmospheric oxygen. The aryl propiolates were regioselectively incorporated into the ring system to afford 2-arylpyridines as the sole product.

We screened α-methylene cyclopentanones (MCPs) for NF-κB pathway inhibitory activity. The conformation of biologically active diastereomers was controllable by the stereochemistry of the side chain.

DPP8/9 inhibition induces either pyroptotic or apoptotic cell death in hematological malignancies. We previously reported that treatment with the DPP8/9 inhibitor 1G244 resulted in apoptotic cell death in myeloma, and our current study further evaluates the mechanism of action of 1G244 in different blood cancer cell lines. Specifically, 1G244 inhibited DPP9 to induce GSDMD-mediated-pyroptosis at low concentrations and inhibited DPP8 to cause caspase-3-mediated-apoptosis at high concentrations. HCK expression is necessary to induce susceptibility to pyroptosis but does not participate in the induction of apoptosis. To further characterize this DPP8-dependent broad-spectrum apoptosis induction effect, we evaluated the potential antineoplastic role for an analog of 1G244 with higher DPP8 selectivity, tominostat (also known as 12 m). In vitro studies demonstrated that the cytotoxic effect of 1G244 at high concentrations was enhanced in tominostat. Meanwhile, in vivo work showed tominostat exhibited antitumor activity that was more effective on a cell line sensitive to 1G244, and at higher doses, it was also effective on a cell line resistant to 1G244. Importantly, the weight loss morbidity associated with increasing doses of 1G244 was not observed with tominostat. These results suggest the possible development of novel drugs with antineoplastic activity against selected hematological malignancies by refining and increasing the DPP8 selectivity of tominostat.