In this study, glycosylation using diphenylphosphinate as a new leaving group was examined. When the glycosylation of various alcohols with acetylated β-D-glucopyranosyl diphenylphosphinate (1) was carried out in the presence of trimethylsilyl trifluoromethanesulfonate in nitromethane, both the corresponding glucosides and the glucosides, which were deacetylated at position 2, were produced. Three kinds of reaction paths through an ortho ester intermediate can be considered for the present glycosylation.

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We focused on neighboring group participation as a key step for controlling the structures of cationic intermediates, and developed a valuable cation precursor, 2, 2-dimethoxyethyl ester, as well as selective reactions directed by a sulfenyl group. It was found that 2, 2-dimethoxyethyl esters generate cyclic cationic intermediates on the action of a Lewis acid via neighboring group participation of the ester function toward the acetal carbon. The cationic intermediates thus generated were useful for the stereoselective Michael reaction as well as the Diels-Alder reaction. The reactions applying neighboring effect of a sulfenyl group were also examined. As a result, stereoselective aldol reactions of the substrates containing a sulfenyl group were developed. Moreover, regioselective pinacol rearrangement and allylation reaction, and stereoselective cationic cyclization could be effectively carried out under the control of a sulfenyl group.

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 This review describes our recent efforts to develop efficient methods for the synthesis of heterocyclic compounds, such as indoles and benzofurans, employing ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes, which were prepared by the reaction of 1,3-cyclohexanediones with sulfonium salts. Ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes with primary amines proceeded at room temperature to provide 2-substituted tetrahydroindol-4(5H)-ones in good to excellent yield. The obtained product was readily converted into a 2-substituted 4-hydroxyindole derivative. Furthermore, acid-catalyzed ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes proceeded smoothly at room temperature to provide 2-substituted tetrahydrobenzofuran-4(2H)-ones in excellent yield. The obtained product was converted into a 2-substituted 4-hydroxybenzofuran derivative. The synthetic utility of this catalytic protocol was demonstrated by the total synthesis of cuspidan B.

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  Multi-substituted β-lactam compounds have not only attracted considerable interest as core structures of pharmaceutical compounds such as antibiotics but also have been used as building blocks for the construction of β-amino acids. Electrophilic β-lactams can be used to enhance essential biological activities. Furthermore, the ring-opening reactions of electrophilic β-lactams can be used to provide facile access to β-amino acids. The introduction of an electronegative fluorine atom to a β-lactam ring to give the corresponding fluoro-β-lactam can be used as an effective strategy for the preparation of electrophilic β-lactams. In this review, we provide a summary of our recent research towards the direct functionalization of fluoro-β-lactams. This review has been divided into four topics, including: 1) the alkylation and hydroxyalkylation of α-bromo-α-fluoro-β-lactams (1); 2) the nickel-catalyzed cross coupling reaction of 1; 3) the asymmetric synthesis of fluoro-β-lactams using chiral ligands; and 4) the utilization of fluoro-β-lactams as highly electrophilic building blocks.

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Glycoproteins, naturally occurring hybrid macromolecules composed of a protein and oligosaccharide chains, show various important biological activities in medical and pharmaceutical sciences. In spite of strong demand for glycoproteins having a definite structure, its specific preparation is still an unsolved problem in the field of synthetic organic chemistry. Here we propose an efficient strategy for synthesis of glycoproteins via 1,2-oxazoline derivatives as glycosyl donors for enzymatic transglycosylation.
We developed a facile method for synthesis of sugar oxazoline derivatives by the intramolecular dehydration reaction of the corresponding unprotected 2-acetamido-sugars in water using 2-chloro-1,3-dimethylimidazolinium chloride (DMC) as a dehydrating agent. According to this method, disialo-oligosaccharides can be converted to the corresponding 1,2-oxazoline derivatives in high yields without protecting the hydroxy groups.
A transglycosylation of the resulting oxazoline derivative to the GlcNAc moiety on a protein has successfully been demonstrated catalyzed by a mutant of N-acetylglucosaminidase-M, giving rise to a monodispersed disialo-type glycoprotein.

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 Nucleic acid-based drugs (NABDs) have recently attracted considerable attention as next-generation medicines, following the development of low molecular-weight and antibody drugs, because it is likely that they will have fewer side effects and greater target specificity than conventional medicines. Short double-stranded RNAs contain a 2-nucleotide overhang at the 3′-end of each strand. Small interfering RNAs (siRNAs) and microRNAs (miRNAs) inhibit gene expression by RNA interference (RNAi) and thus have great potential as NABDs. However, naked RNA strands have many problems that hinder their application as therapeutics, such as their rapid degradation in biological fluids, poor cellular uptake, and off-target effects. Therefore, artificially modified siRNAs and miRNAs have been studied extensively in an effort to overcome these problems. In this review, I summarize my recent studies on the synthesis of nucleic acid mimics and their application in RNAi-based medicine. The following two topics are specifically discussed: 1) the design and synthesis of chemically modified functional RNAs bearing nucleic acid mimics at their 3′-overhang region, which plays a key role in RNAi; and 2) the practical, reliable synthesis of nucleic acid mimics containing ethynyl groups.

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Azaspiracids (AZAs) are a group of shellfish toxin responsible for the poisoning called "azaspiracid poisoning (AZP)" prevailed in a coastal region of north Europe to northwest Africa since 1995. To establish the molecular basis including its chemical structure and its mode of biological action, several synthetic studies have been developed on azaspiracid-1 (AZA-1). In this review, studies on the syntheses of the FGHI- and EFGHI-ring domains corresponding to a lower half of AZA-1, reported by groups of Forsyth, Evans, Nicolaou, and us, are summarized. Retrosynthetic analysis, fragment synthesis and their assembly, and stereoselective construction of the unique spiroaminal HI-ring domain are main topics of this review. Furthermore, total syntheses successfully made by Evans and Nicolaou groups are described.

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A great number of protective groups for hydroxyl function have played an important role in organic synthesis particularly in the degradation or transformation of natural products and in the synthesis of polyfunctional molecules. Various types of protective groups for hydroxyl function have been exploited and are classified mostly into alkyl ether-, silyl ether-, acetal-, and ester-types. It is frequently needed to transform an existing protective group to another one pretinent to the following steps in the course of total synthesis of complex natural products such as carbohydrates and macrolide antibiotics, and this usually calls for two separate steps, i.e. a deprotection and a protection-anew. It will therefore be of great benefit in view of time and material savings to have means of one-step transformations between protective groups. From this viewpoint, I wish to demonstrate novel and efficient methods for one-step conversion of protective groups of hydroxyl function.

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β-（1,3）-グルカンは免疫賦活作用を有するため、古くから抗ガン剤として利用されてきた。しかし、β-（1,3）-グルカンがその活性を示すメカニズムは、まだ明らかにされていない。その大きな要因はメカニズムの解明を行うために利用されてきたβ-（1,3）-グルカンが、天然から抽出した構造が不均一な混合物であるためである。そのため、構造が明確なβ-（1,3）-グルカンは、生物活性におけるβ-（1,3）-グルカンの効果を単純化するために必要であり、そのβ-（1,3）-グルカンの化学合成に関する研究が行われてきた。グルコースの3位ヒドロキシ基の反応性は、グルコースの4位ヒドロキシ基の保護基の立体障害により、大きく低下しているため、β-（1,3）結合を形成するグリコシル化は困難である。さらに、6位に分岐鎖をもつβ-（1,3）-グルカンオリゴ糖を合成するためには、2つのヒドロキシ基に選択的に糖を導入できる保護基の選択が重要であり、グリコシル化に対する保護基の組み合わせによる影響を考慮して最適化しなければならない。近年、4,6-O-ベンジリデン基を導入した糖供与体と糖受容体を用いたβ-（1,3）-グルカンオリゴ糖の合成に関する研究が精力的に行われ、糖受容体の反応性とβ-（1,3）グリコシル化の立体選択性は大幅に改善された。その結果、直鎖状のβ-（1,3）-グルカンは16糖まで合成可能となった。また、β-（1,3）-グルカンの直鎖の骨格に分岐鎖を複数導入する方法に関するいくつかの有望な例が報告された。さらに化学合成したβ-（1,3）-グルカンオリゴ糖を用いた応用研究がすでにいくつか行われている。

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In recent years, hypervalent iodine reagents have gained increasing popularity in metal-free oxidative transformation due to their low toxicity, easy handling, transition-metal-like reactivity, and other benefits. However, although metal-free oxidative transformations of alkynes using iodine (III) reagents have been well studied for the preparation of alkynyl (aryl) iodonium and alkenyl (aryl) iodonium salts, stepwise methods including preparation step of these iodonium species have been commonly used in the synthesis of heterocycles from alkynes. In this account, our two approaches to the metal-free and single-step synthesis of heterocycles via an activation of alkynes by iodine (III) are mainly described. One is iodine (III)-mediated/catalyzed oxidative cycloisomerization reactions of propargyl compounds for the preparation of heterocycles bearing various functional group at their side chains. In these reactions, iodine (III) species works as an activator of carbon-carbon triple bonds as well as a donor of various heteroatomic functional groups. This methodology can be extended to iodine (III)-mediated/catalyzed oxidative annulation of alkynes and nitriles as another approach, in which heteroatoms on iodine (III) species are incorporated in the azole rings. In addition, molecular iodine-catalyzed cyclization of o-alkylanilines via iodocyclization/proto-deiodination sequence is described as an iodine catalysis without terminal oxidants.

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Nucleic acids bridged between 2’- and 4’-positions are attracting much attention because the oligonucleotides bearing these derivatives generally increase in the binding affinity with single-stranded RNA and have an increased resistance against nuclease. It is found that their properties are greatly affected by size and composition of the bridge. In particular, introduction of heteroatom into the bridge unit is considered to give an influence on network of surrounding water molecules in formation of nucleic acid complex. Therefore, it would be meaningful to investigate and understand the properties of various 2’,4’-bridged nucleic acids. Under such a background, this account focuses on 2’,4’-bridged nucleic acids containing multiple heteroatoms in the bridge structures, with five-, six- and seven-membered bridges, have recently been reported by us, and the synthesis, duplex-forming ability with single-stranded nucleic acid and nuclease resistance of their modified oligonucleotides are mainly described.

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