The ammonium betaine was developed as an intramolecular ion-pair catalyst for realizing cooperative catalysis of a cation and anion; i.e. ion-pair catalysis. Combination of the stereocontrolling ability of the chiral ammonium ion and functions of the pairing aryloxylate ion enabled bifunctional organic base catalysis and ionic nucleophilic catalysis, which facilitate a variety of organic transformations with rigorous stereochemical control. In addition, employing a single-electron-accepting cation as a partner of the basic aryloxylate led to the development of a chemical redox catalyst with the capability of proton-coupled electron transfer (PCET). This research demonstrates a power of the ion-pair catalysis in selective organic synthesis and is therefore likely to stimulate further study in this field.

Flavan-derived polyphenols are widely distributed in the plant kingdom, and have long been known to possess remarkable biological activity and a positive effect on human health. However, the detailed biochemical functions of this class of molecules at a molecular level are still not well studied due to the limited availability of natural samples in sufficient quantity and quality. This account gives an overview of our synthetic efforts towards this class of molecules which exploit selective functionalization of the C(4) position of the flavan skeleton. Various nucleophilic components could be introduced into this position via S_N1-type substitution. As part of our synthetic studies on flavan oligomers, an orthogonal activation method that employs two distinct flavan units was developed. This enabled iterative coupling to give linear and/or doubly-linked flavan oligomers to be achieved.

Asymmetric catalysis is one of the most attractive and efficient approaches toward synthesis of chiral enantioenriched compounds using achiral compounds as substrates and reagents. Compared with the well-established enantioselective preparation of carbon-stereogenic compounds, the corresponding preparation of silicon-stereogenic compounds is much less explored. In fact, most of the available methods rely on the use of stoichiometric amounts of chiral reagents, and much less progress has been made on catalytic enantioselective synthesis from achiral compounds. This review article mainly focuses on our recent achievements in this research area through the use of a synthetic strategy that employs transition-metal-catalyzed enantioselective desymmetrization reactions of prochiral tetraorganosilanes.

In this study, the total syntheses of apratoxins A and C and their analogs were carried out. Apratoxins A and C and their oxazoline analogs exhibited potent cytotoxicities against cancer cells as well as similar 3D structures in solution as analyzed by a distance geometry method. The oxazoline analogs were slightly less, but highly, potent as they exhibited similar conformations as their parent compounds. As the MoCys moiety possibly induced severe toxicity owing to the ability of a Michael acceptor and instability of the thiazoline ring under acidic and basic conditions, MoCys and MeAla-MeIle were substituted by other simple amino acids. In addition, the combinatorial synthesis of these mimetics was carried out by the split and mix method with solid-phase peptide synthesis and solution-phase macrolactamization in parallel. Apratoxin M7 in which MoCys was replaced by piperidine-4-carboxylic acid was found to exhibit a conformation similar to that of apratoxin A, and indicated moderate activity. Based on apratoxin M7, the further optimization of the Tyr(Me)-MeAla-MeIle tripeptide led to the discovery of apratoxin M16 (Bph/Tyr(Me)), which is as potent as apratoxin A. The growth inhibitory activity of apratoxin A and apratoxin M16 against 10 cancer cell lines was comparable, suggesting that the target of apratoxin M16 should be the same as that of apratoxin A.

Thienoquinoids are a class of compounds that consist of a quinoidal conjugation path in the thiophene-based π-extended structures. Owing to the quinoidal conjugation path, the characteristic features of thienoquinoidal compounds are their high-lying energy levels of the highest occupied molecular orbitals (HOMOs) and low-lying energy levels of the lowest unoccupied molecular orbitals (LUMOs) compared to their aromatic thiophene-based counterparts. The thienoquinoidal cores are often terminated with electron-withdrawing groups such as dicyanomethylene units, which further lowers the LUMOs making the resulting thienoquinoidal compounds attractive as electron-accepting molecules for charge-transfer complexes and n-type organic semiconductors. In fact, the thienoquinoidal molecules were initially focused as the electron accepter in 1980s. Since 2002 when the first report that a terthienoquinoidal derivative can act as a superior n-type organic semiconductor, this class of compounds have attracted researchers in the field of organic electronics and organic semiconductors, and a vast number of thienoquinoidal molecules have been synthesized in the last decade. The present review focuses on the methods for the synthesis of thienoquinoidal compounds with different terminal units and their electronic structures depending on the terminal units and thienoquinoidal cores. Then, several representative results on the application of thienoquinoidal molecules in the n-type field-effect transistors are mentioned, together with future prospects of this intriguing class of compounds.

Catalytic synthesis of heteroles via the cleavage of carbon-heteroatom bonds is described. The rhodium-catalyzed reaction of 2-silylphenylboronic acids with internal alkynes gives 2,3-disubstituted benzosilole derivatives with loss of a substituent in the triorganosilyl group of the staring material. π-Extended phospholes and thiophenes were found to be synthesized by the palladium-catalyzed reactions of normally unreactive tertiary phosphines and sulfides through the cleavage of carbon-phosphorus and carbon-sulfur bonds, respectively. In addition, double cleavage of carbon-phosphorus bonds of bisphosphines is found to occur with the generation of phospholes.

Over 40 years have passed since a well-known hypothesis of a channel-like amphotericin B (AmB) assembly with ergosterol (Erg) was proposed as the mode of action accounting for its selective fungal toxicity. However, no reliable or direct experimental evidence had been obtained until recently mainly because of significant difficulties in structural analysis of the self-assembly of small molecules specifically formed inside a membrane. In this study, we describe the accomplishments in the chemical synthesis of two AmB derivatives with fluorine labeling in the molecular skeleton for applying solid-state NMR techniques. The interatomic distance measurements using these chemically prepared probes have successfully shown the detailed AmB-Erg bimolecular interaction in the channel structure for the first time. The latest solid-state NMR analysis backed by synthetic chemistry is expected to achieve a breakthrough in elucidating the long-unsolved AmB channel architecture.

Nitrogen and phosphorus are ubiquitously found in biologically active compounds, natural products, pharmaceutical agents, synthetic reagents, and even organic functional materials. The introduction of these heteroatoms into organic skeletons by the development of C-N and C-P bond forming reactions has been one of the long-standing research goals of synthetic chemistry. Both nitrogen and phosphorus have one lone pair, and synthetic chemists have therefore developed many nucleophilic amination and phosphination reactions. On the other hand, our research group has recently been focusing on the unique reactivity of hydroxylamines and hydroxylphosphines (tautomers of secondary phosphine oxides), and has developed otherwise challenging C-N and C-P bond-forming reactions with alkenes and alkynes based on electrophilic amination and phosphination using these reagents. In this account, we present an umpolung-enabled, copper-catalyzed, regio- and stereoselective aminoboration and hydroamination of alkenes, including unactivated terminal alkenes as well as electronically and sterically activated styrenes, strained alkenes, and vinylboranes/silanes. Additionally, a similar umpolung, electrophilic phosphination of alkynes under Tf₂O-promoted, metal-free conditions is also described.

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes. Unfortunately, current therapeutic agents are not so effective that only less than 36% of the patients have been treated satisfactorily. Thus, we set out to investigate novel small-molecule carbohydrate mimics as potential antidiabetic agents to supplement the existing medication. Selective inhibition of the transporter protein sodium-glucose cotransporter 2 (SGLT2) has emerged as a promising way to control blood glucose level in T2DM patients. We have pioneered the design and synthesis of some novel carbasugars (pseudosugars), readily available from inexpensive ᴅ-gluconolactone, which contains a metabolically stable “pseudo-glycosidic” C-O bond. Their aza-analogues (with a C-N bond) and carbon-analogues (with a C-C bond) have been prepared to provide important insights into the structure-activity relationship (SAR) of these inhibitors, thereby aiding the development of carbasugar SGLT2 inhibitors as potential antidiabetic agents. Our synthetic targets are the carbocyclic analogues of sergliflozin and dapagliflozin, which are readily accessible via various transition metal-catalyzed cross-coupling reactions. We herein describe our novel synthetic approaches towards carbasugar SGLT2 inhibitors, and discuss their SAR.

This account focuses on the synthesis and reactivity of the diborane(4) compounds, pinB-BMes₂ and B₂(o-tol)₄ (pin = pinacolato, Mes = 2,4,6-Me₃C₆H₂, o-tol = 2-MeC₆H₄), which have been recently reported by the author’s group. Both compounds exhibit higher Lewis acidity than the most common diborane(4) B₂pin₂, which is due to the overlapping vacant p-orbitals of the two boron atoms. As a result, pinB-BMes₂ and B₂(o-tol)₄ exhibit a peculiar reactivity toward multiple bond compounds and small molecules such as CO, isocyanides, alkynes, nitriles, pyridine, and H₂. DFT calculations revealed that the combination of the high electrophilicity of these diborane(4)s, which facilitates the complexation of weak nucleophiles, and the reactive B-B bonding electrons should be responsible for the observed unique reactivity.

This essay summarizes a personal history of studies on fluoride-mediated reactions of enol silyl ethers, metal homoenolate, cytochalasin and cortisone synthesis, cycloaddition chemistry of cyclopropenone acetals and dipolar trimethylenemethanes, biological activity of organofullerenes and DNA and siRNA delivery, organocuprate(I) reaction mechanisms, iron-catalyzed cross coupling and C-H activation reactions, ¹⁵O labeling for positron emission tomography (PET), functional fullerene molecules including bucky ferrocene, shuttlecock molecules and [10]cyclophenacene, fullerene bilayer vesicles, new design materials for organic and lead perovskite solar-cell fabrication, carbon-bridged oligophenylene vinylenes and single-molecule atomic-resolution real-time transmission electron microscopy (SMART-EM) for structural and kinetic studies of molecules and molecular clusters. It also describes how the encounters with key people may change the course of your scientific research as well as of your personal life. These examples suggest that life is a stochastic process, and, moreover, science in the future would be something that we do not even imagine now as a subject of research.