Go Hirai

Sialidase-resistant ganglioside analogues having biological activities similar to those of natural gangliosides are expected to be important probes for clarifying the biological functions of gangliosides. Focusing on difluoromethylene-linked (CF2-linked) α(2,3)sialylgalactose as a core structure of sialidase-resistant ganglioside mimics, we have developed novel, stereocontrolled, and efficient methodologies to synthesize CF2-sialosides based on Ireland−Claisen rearrangement. CF2-linked α(2,3)sia

<i>C</i>-Glycosides are metabolically stable mimics of natural <i>O</i>-glycosides and are expected to be useful tools for investigation of the biological functions of glycans. Here, we describe the synthesis of a series of aryl and vinyl <i>C</i>-glycosides by stereoinvertive sp³-sp² cross-coupling reactions of 2-deoxyglycosyl boronic acid derivatives with aryl or vinyl halide, mediated by a photoredox/nickel dual catalytic system. Hydrogenation of the vinyl <i>C</i>-glyco

C-Linked carbohydrate structure, in which the cleavable O-glycosidic linkage is replaced by a carbon unit, is a useful tool for functional analyses of glycoconjugates. We describe a synthetic method for α-CH₂-linked disaccharide structures, such as Glc(1,6)-Glc, by stereoselective radical-coupling C-glycosylation between a conformationally constrained and stable C1-sp³ hybridized xanthate donor and a carefully designed acceptor.

[reaction: see text]. Stereocontrolled synthesis of the ABC ring framework of zoanthenol has been achieved. Our studies show that a beta,beta-disubstituted enone can act as a good acceptor of arylpalladium intermediates in the formation of a congested benzylic quaternary carbon center through an intramoleculer Mizoroki-Heck reaction. The cis B/C ring system was stereoselectively converted to the trans-fused framework through a SmI2-promoted deoxygenation of the alpha-hydroxy ketone.

We describe a new synthetic approach for C-linked glycolipid analogues, in which the cleavable O-glycosidic linkage is replaced by a carbon unit. Direct C-glycosylation of a conformationally constrained and stable C1-sp³ hybridized xanthate carbohydrate with carefully designed sphingosine units afforded the CH₂-linked analogue of antitumor-active KRN7000 and its glucose congener.

The acetal (<i>O</i>-glycoside) bonds of glycans and glycoconjugates are chemically and biologically vulnerable, and therefore <i>C</i>-glycosides are of interest as more stable analogs. We hypothesized that, if the <i>O</i>-glycoside linkage plays a vital role in glycan function, the biological activities of <i>C</i>-glycoside analogs would vary depending on their substituents. Based on this idea, we adopted a "linkage-editing strategy" for the creation of glycan analogs (pseudo-glycans). We de

Glycoconjugates are an important class of biomolecules that regulate numerous biological events in cells. However, these complex, medium-size molecules are metabolically unstable, which hampers detailed investigations of their functions as well as their potential application as pharmaceuticals. Here we report sialidase-resistant analogues of ganglioside GM3 containing a monofluoromethylene linkage instead of the native <i>O</i>-sialoside linkage. Stereoselective synthesis of <i>CHF</i>-linked di

Phosphate Surrogate: A potent vaccinia H1-related (VHR) phosphatase inhibitor with a nonacidic core structure has been developed. RK-682 enamine (RE) derivatives were found to be dual-specificity protein phosphatases (DSP)-selective and cell-permeable. The most VHR-selective compound, RE12, induced cell-cycle arrest in NIH3T3 cells at G1 phase and inhibited dephosphorylation of VHR substrates, such as phospho-ERK and phospho-JNK.

Abstract Stereo-controlled construction of the C-ring model (4) of zoanthamine alkaloids was achieved via a SmI2-mediated Simmons-Smith reaction.

Abstract The reactions of fluorinated ylide, generated from tris(dimethylamino)phosphine and tribromofluoromethane, with simple aldehydes and reactive ketones gave the expected Wittig reaction products. However, a ketone having a galactose skeleton afforded an acid fluoride, probably through an unprecedented Corey–Chaykovski-type epoxide formation reaction, followed by spontaneous Meinwald rearrangement.

We present a full account of our synthetic studies on the racemic DEFGH-ring moiety of physalins, featuring domino ring transformation of a tricyclic key intermediate. We also report the results of a detailed mechanistic examination of the domino ring transformation, as well as a reoptimization of the 2,3-Wittig rearrangement and methylation steps. Furthermore, we have newly established a method for the preparation of an optically active synthetic intermediate by enzymatic kinetic resolution. Ou

Synthesis of a focused library is an important strategy to create novel modulators of specific classes of proteins. Compounds in a focused library are composed of a common core structure and different diversity structures. In this Account, we describe our design and synthesis of libraries focused on selective inhibitors of protein phosphatases (PPases). We considered that core structures having structural and electronic features similar to those of PPase substrates, phosphate esters, would be a

Substituent direction is important: Type A–D isobenzofuranone derivatives were synthesized with differently directed hydrophobic alkyl side chains. These ligands bind in a similar conformation to protein kinase Cα but have contrasting activation abilities, possibly owing to different interaction of the side chain with the membrane lipid. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2452/2007/z700080_s.pdf or from the author. Please not