Messenger RNA (mRNA) is gaining attention as a new modality of oligonucleotide therapeutics. We have reported a new mRNA synthesis method, named the PureCap method, by in vitro transcription, which enables the production of completely capped mRNA. For this purpose, we designed and synthesized new cap analogs bearing hydrophobic o-nitrobenzyl groups, which function as purification tags for mRNA with a 5′-cap structure by reverse-phase high-performance liquid chromatography. In this paper, we describe the synthesis of new cap analogs, named PureCap analogs, and its application for completely capped mRNA synthesis.

Ensitrelvir, SARS-CoV-2 3CL protease inhibitor, has been discovered for the treatment of the coronavirus disease 2019 (COVID-19). Ensitrelvir is structurally composed from three main units, which are indazole unit, triazole unit and triazinone unit. Synthetic strategies where these three units are employed at latter steps in the synthesis made it possible to construct a highly productive convergent route. In addition, the lean manufacturing process was also established through process optimization based on SELECT perspectives. These achievements contributed for the rapid commercial manufacturing of Ensitrelvir with less than one year. In this report, we describe R&D activities for route scouting and process optimization. In addition, a few trouble shootings which occurred during the manufacturing are also introduced. Lastly, additional study for further investigations to improve productivity and flexibility are briefly explained.

The synthesis of fluorescent organic molecules with superior luminescent properties is a highly active research area due to their extensive applications in life sciences for fluorescence imaging and in materials science for organic electroluminescence. Even though molecules exhibit efficient luminescence in dilute solution, they often experience concentration quenching in aggregated or solid states. However, recent advancements have led to an increase in solid-state-emissive organic molecules by suppressing intermolecular interactions or utilizing aggregation-induced emission. Some of them exhibit mechanochromic luminescence (MCL), where emission color changes reversibly in response to mechanical stimuli, such as grinding with a spatula. In typical MCL of organic crystals, mechanical stimuli induce amorphization and a red shift in emission wavelength. Subsequent stimuli, like heating or solvent exposure, restore the original emission color. Initially, designing organic crystals with MCL properties was challenging and relied on serendipity. This paper summarizes research on the syntheses of stimuli-responsive luminescent organic molecules, particularly those exhibiting MCL in the crystalline state. By synthesizing various donor-acceptor-type luminescent molecules, the steric effects of substituents were found to significantly influence luminescent properties and mechanoresponsive behavior in the crystalline state. Additionally, creating segregated crystals by mixing pyrene derivatives with other luminescent molecules enhanced the mechanoresponsive shift in emission wavelength. Furthermore, utilizing asymmetric synthesis of secondary alcohols, chiral bispyrene derivatives were developed that enabled the switching of circularly polarized luminescence. These findings represent significant achievements in the rational control of luminescence in organic molecules and have substantial implications for advancing synthetic organic chemistry, photochemistry, and materials science.

Organic synthetic molecules and supramolecular assemblies that respond to a large variety of external stimuli, such as solvent, temperature, photoirradiation, pH, and mechanical forces (pressure, stress, strain, and tension), have attracted considerable attention in current chemistry. Such smart soft materials, or chemosensors, have potential applications in interfacial imaging, probing, and cancer detection, which necessitate stimuli-responsive structural/optical/functional changes. In recent years, there has been significant progress in the synthesis of dynamically controllable chemosensors in response to external stimuli. In particular, hydrostatic pressure, one of the mechanical isotropic forces, has gained attention in the field of “mechano” science (mechanochemistry and mechanobiology), where pressure-responsive chemosensors are strongly desired for detecting minute pressures in cancer cells. Indeed, based on the hydrostatic pressure-control concept, we have successively developed pressure-responsive functional soft materials that show (chir) optical changes. For example, notable examples include the flapping porphyrin tweezers with S₂ fluorescence, the dynamic polymers with aggregation-induced emission, the biocompatible polymers with excimer fluorescence, and other various systems, all of which exhibit spectral responses under the influence of hydrostatic pressure. These discoveries have motivated us to develop a further practical chemosensor that can be controlled by hydrostatic pressure. In this review, we summarized our recent achievements on the pressure-responsive chemosensors.

Small polyhedral hydrocarbons represented by cubane have attracted attention as potential molecular scaffolds for pharmaceuticals as benzene bioisostere. Cubane is also expected to be used as a chiral scaffold, but due to its high symmetry, it is necessary to introduce chirality by sequential site-selective introduction of substituents. Furthermore, polyhedral desymmetrized isomers of cubane, such as cuneane and semibullvalene, and extended cage compounds, such as bishomocubane and homocuneane, exhibit chirality and are also expected to be used as new chiral scaffolds. In this concept, we would like to explain our synthetic routes, particularly focusing on the decoration and editing of the cubane skeleton.

In this minireview, digital microfluidics (DMF) is presented as an innovative option for automated organic synthesis at the microscale. Using DMF, valuable compounds, were successfully synthesized at the microliter scale. Additionally, organic reactions within the DMF devices were monitored using microcoil NMR and electrostatic spray ionization, allowing for kinetic analysis of rapid reactions. As DMF technology continues to advance and be integrated with synthetic organic chemistry, further miniaturization, automation, and acceleration of organic synthesis processes are anticipated.