We herein describe an umpolung carboxylation of allyl alcohol derivatives, which is efficiently catalyzed by a palladium catalyst. This carboxylation with CO₂ is extended to several substrates including vinylcyclopropanes, N-allenyl-2-iodoanilines, indole, furan, and pyrrole derivatives, which are all converted into nucleophilic allylpalladium species in the presence of ZnEt₂ and then react with CO₂. Among them, when 2-indolylmethyl, 2-furylmethyl, and 2-pyrrolylmethyl acetates were employed, unprecedented double carboxylations took place to afford the corresponding dicarboxylated products in good yields. These strategies are powerful for synthesizing various carboxylic acids from readily available starting materials and their synthetic utilities are very broad.

Progress in genome-guided discovery of secondary metabolites has facilitated the identification of naturally occurring polyene macrolactams and their polycyclic lactam derivatives from microorganisms. Recent studies revealed that some transformations from parent macrolactams to their polycyclic derivatives proceeded without the aid of enzymes and were only dependent on external environmental stimuli such as light irradiation, heating, and aerobic conditions. Interestingly, some polyene macrolactams such as heronamide C and niizalactam A are converted in response to the different stimuli into polycyclic lactams with different polycyclic skeletons and biological activity. We have regarded such compounds as “pluripotent stem molecules” and have been working on not only the chemical and reactivity analysis of these molecules but also the creation of their synthetic versions, which we named “induced pluripotent small (iPS) molecules” after iPS cells. In this account, we review the structure, reactivity, biogenesis, and biological activity of naturally occurring polyene macrolactams. Our current efforts toward creating iPS molecules based on naturally occurring polyene macrolactams are also discussed.

Sirtuins (SIRTs) are a family of NAD⁺-dependent histone deacetylases. In mammals, dysfunction of SIRTs is associated with age-related metabolic diseases and cancers, so SIRT modulators are considered to have potential therapeutic values. For a long time, it was thought that SIRTs only catalyze deacetylation reactions of histones, however, more recently, it was found that SIRTs can remove various acyl groups, including propionyl, crotonyl, succinyl, hexanoyl, myristoyl, palmitoyl, lipoyl and benzoyl groups, from histones and many other protein substrates. In addition, recent reports suggest that SIRT6 demyristoylase activity regulates the secretion of TNF-α, and that SIRT2 defatty acylase activity regulates the localization of K-Ras4a oncoprotein and promotes cellular transformation, meaning that new enzymatic activities of SIRTs also regulate pathophysiological functions. Therefore, SIRT-subtype- and activity-specific fluorescence probes and modulators are required both as tools for basic research to understand the physiological functions of SIRTs and as candidate therapeutic agents. In this review article, we first describe the molecular design and development of a new fluorescent probe for one-step SIRT activity detection and their application to cellular SIRT1 imaging. We then outline a strategy for converting fluorescent probes to peptide inhibitors based on the findings obtained in the course of developing the fluorescent probes. We further describe the construction of a fluorescent probe library with different isozyme selectivity among SIRTs was used to select the best fluorescent probe for detecting SIRT2 activity, which was then applied to chemical screening to search for small-molecular inhibitors of SIRT2 demyristoylase activity.

Open-shell π-electronic molecules exhibit spin and magnetic properties, facile redox properties, and unique photophysical properties derived from their unpaired electron(s) and the presence of singly-occupied molecular orbital(s). Especially, stable open-shell π-electron molecules are continuously attracting attention in interdisciplinary research areas as promising components of magnetic, electric, and related materials. Among them, radical cation species generated by oxidation of π-electron molecules with superior electron donating ability are one of the promising components of the materials because their physical properties and functionality of molecular entities and assemblies are able to be controlled by substituents and counter anions. Here, we have introduced detailed molecular structures and intriguing physical properties of highly stable radical cations based on phenothiazine, dihydrophenazine, and phenoxiazine π-electronic systems, such as controls of magnetic, near-IR absorption, and liquescent properties, that have been elucidated as results of our continuous research.

Organometallic complexes have proven to be useful in synthetic organic chemistry over the decades. Their definition is molecular compounds with metal-carbon interaction(s) or precursors. Typically, organometallic compounds are prone to hydrolysis, and thereby they have been considered to be less compatible with biological environments, where water is abundant. On the other hand, the past few decades have witnessed the structural identification of metal-sulfur clusters with metal-carbon bond(s) in the active sites of enzymes, which reduce small substrates such as N₂, protons, and CO₂. The structure-function relationship of such “organometallic” metal-sulfur clusters would provide clues to develop a new class of catalysts for the transformation of small molecules, including organic substrates. In this review article, we summarize recent progress in the reaction chemistry of metal-sulfur clusters, with particular emphasis on the reduction and transformation of N₂, CO₂, and small organic molecules.

Carbon dioxide radical anion (CO₂^·−) is a reactive intermediate that can act as a powerful single electron reductant as well as a nucleophilic C1 radical source. However, its utility has not been well explored due to the fact that direct reductive approaches to access CO₂^·− from thermodynamically stable CO₂ require deeply reducing conditions. This review focuses on a recently developed approach for the generation of CO₂^·− via hydrogen-atom transfer under practical and mild conditions, which has enabled a variety of transformations that are difficult to achieve by conventional methods.