Sodium-dependent glucose transporter 2 (SGLT2) inhibitors suppress reabsorption of filtered glucose in renal proximal tubule. Therefore, the inhibitors can control blood glucose by excreting the excess glucose in the urine. Six SGLT2 inhibitors have already been approved in Japan for type 2 diabetes treatments. The structural feature is that sugar is directly connected to benzene. Starting with dapagliflozin, pioneering C-glucoside, a modification of the aglycon and the sugar moiety has been made and the various preparation methods are developed. This review focuses on the sophisticated organic chemistry of C-glucoside construction.
Substitution of parts of C=C double bonds of conjugated hydrocarbons with electronegative and isoelectronic C=N moieties often causes drastic improvement in solubility in organic solvent, stability toward air or moisture, and electron-accepting ability. Therefore, aza-containing π-conjugated compounds nowadays constitute a significantly important family of organic functional materials, and thereby much attention has been paid to the elaboration on the development of efficient and selective synthetic methods of such compounds over the last few decades. Recently, we have developed novel synthetic methods of aza-containing π-conjugated compounds that are otherwise difficult to access by conventional methods, starting from aromatic amines as useful building blocks. In this account, the developed reactions along with the physicochemical properties of the novel conjugated compounds are described.
One-pot oxidation from primary alcohols to carboxylic acids is one of the most important methods in organic synthesis. With attention to the mechanistic advantage of Merck’s method (cat.2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)/cat.NaOCl/NaClO2), we have developed an efficient one-pot oxidation using 1-Me-AZADO+X-(oxoammonium salt of 1-methyl-2-azaadamantane N-oxyl) and NaClO2. After that, our research interest was focused on selective oxidation from diols to hydroxy acids. Herein, we report development of a highly active oxidation catalyst for selective oxidation of primary alcohols, 1,5-dimethyl-Nor-AZADO (DMN-AZADO), and DMN-AZADO-catalyzed selective oxidation of diols to hydroxy acids, and also report the chemoselective oxidation of 1,2-diols to α-hydroxy acids together with the one-pot oxidative cleavage from 1,2-diols to one-carbon-shorter carboxylic acids. A mechanistic study suggests that the formation of charge-transfer complex TEMPO-ClO2 is a key for the observed chemoselectivity.
Due to the depletion of fossil fuels, natural carbon resources (i.e. biomass-derived sugars) have attracted increasing attention in recent years as an alternative carbon source. Although significant advances have been reported in the development of catalysts for the conversion of carbohydrates into key chemicals, only a limited range of products can be obtained. We herein describe the highly-selective cascade syntheses of a range of useful compounds using biomass-derived sugars and their decomposed oxygenates. We especially focus on the upgrade of C1 and C3 oxygenates generated from glucose, formaldehyde and 1,3-dihydroxyacetone, respectively, to yield useful compounds via C-C bond formation. The establishment of this novel synthetic methodology to generate valuable chemical products from saccharides and their decomposed oxygenated materials renders carbohydrates a potential alternative carbon resource to fossil fuels.
Carbohydrates on proteins play various essential biological roles, such as fertilization, cell adhesion, cell differentiation. However, to understand these biological processes in more detail, proteins with homogeneous carbohydrate are required. The glycan chains of natural glycoproteins are highly heterogeneous, as they are formed by the action of various glycosyl transferases and glycosidases without appropriate templates. On the other hand, expression system using E. coli can not produce glycoproteins, as it does not have glycosylation machinery. These facts result in the lack of an efficient access to homogeneous glycoproteins, which makes the functional analysis of glycoproteins difficult. Due to the recent advances of peptide and glycoscience, the chemical synthesis of homogeneous glycoproteins has become practical. In this paper, I describe recent results of our glycoprotein synthesis.
Recently, the development of selective and powerful inhibitors for enzymes and receptors by structural basis chemical biology is desired. The development has been made successfully by addition of potential to form covalent-linkage with the target-protein to affinity component. Michael acceptors are a powerful and hopeful function to introduce a potential of the covalent-linkage formation to the anticancer agents. This short review describes several recent examples utilizing the covalent-linkage based on the Michael addition reaction in vivo and a possibility of reversible control of the adduct formation.
Imaging mass spectrometry (IMS) is newly developed method for visualizing the distribution of drugs and biomolecules in organ. Imaging mass microscope, iMScope TRIO is the new instrument for MALDI imaging MS (IMS) with high spatial resolution than ever.
In this report, we demonstrated the successfully visualized drugs from the dosed mice organ.