Published papers

© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim The first total synthesis of terpioside B (1) has been accomplished. Key steps include the stereoselective installments of a set of challenging 1,2-cis-glycosidic linkages. Thus, α(1,4)-linked d-galactoside was effectively constructed from a 1,2-anhydrogalactose donor and an unprotected 1,6-anhydrogalactose acceptor by using a boron-mediated aglycon delivery (BMAD) method. In addition, α-l-fucofuranosides were stereoselectively and simultaneously constructed by remote group-assisted 1,2-cis-α-stereoselective glycosylations.

© 2020 The Royal Society of Chemistry. Photo-induced glycosylations of several acceptors with trichloroacetimidate donors using bis(2-naphthyl)disulfide as an organo-Lewis photoacid (LPA) catalyst proceeded effectively to give the corresponding glycosides in good to high yields. In addition, the ground and excited state absorption spectra of bis(2-naphthyl)disulfide with or without NEt3 suggested the Lewis acidity of bis(2-naphthyl)disulfide upon photo-irradiation.

Mannosylerythritol lipids (MELs), which are one of the representative sugar-based biosurfactants (BSs) produced by microorganisms, have attracted much attention in various fields in the sustainable development goals (SDGs) era. However, they are inseparable mixtures with respect to the chain length of the fatty acids. In this study, self-assembling properties and structure-activity relationship (SAR) studies of recovery effects on damaged skin cells using chemically synthesized MELs were investigated. It was revealed, for the first time, that synthetic and homogeneous MELs exhibited significant self-assembling properties to form droplets or giant vesicles. In addition, a small difference in the length of the fatty acid chains of the MELs significantly affected their recovery effects on the damaged skin cells. MELs with medium or longer length alkyl chains exhibited much higher recovery effects than that of C18-ceramide NP.

Development of an efficient method for the analysis and identification of the target proteins with which biologically active glycosides directly interact is highly desirable in many research fields. In this article, we report an efficient strategy for the preparation of chemical probes of biologically active glycosides using a reaction sequence of i) a boron-mediated aglycon delivery (BMAD) with an N3-functionalized 1,2-anhydroglu-cose donor, ii) deprotection, and iii) strain-promoted azidealkyne cycloaddition. Using the synthesized chemical probes, we successfully demonstrated that the target proteins of a cardiac glycoside, lanatoside C (1), can be visualized and identified in human colon cancer HCT116 cells.

Synthesis of three types of purpose-designed mannosylerythritol lipid (MEL)-D analogues with decanoyl groups (C10), β-GlcEL-D, α-GlcEL-D, and α-MEL-D, was accomplished utilizing our boron-mediated aglycon delivery (BMAD) methods. Their self-assembling properties, recovery effects on damaged skin cells, and antibacterial activity were evaluated. It was revealed, for the first time, that α-GlcEL-D and α-MEL-D only generated giant vesicles, indicating that slight differences in the steric configuration of an erythritol moiety and fatty acyl chains affect the ability to form vesicles. Analogue α-MEL-D exhibited significant recovery effects on damaged skin cells. Furthermore, α-MEL-D exhibited antibacterial activity as high as that for MEL-D, indicating that α-MEL-D is a promising artificial sugar-based material candidate for enhancing the barrier function of the stratum corneum, superior to a known cosmetic ingredient, and possesses antibacterial activity.

Here reports an photoinduced glycosylation of trichloroacetimidate donors and several alcohols using 3,11-dimethoxydinaphthothiophene as an organo Lewis photoacid catalyst upon long-wavelength UV-LED light (385 nm) irradiation. The reaction proceeded under mild reaction conditions smoothly to give the corresponding glycosides in good to high yields. In addition, the present glycosylation method was applicable to a wide range of trichloroacetimidate donors and acceptors. Furthermore, the dinaphthothiophene catalyst could be recovered and reused without any loss of efficiency. Moreover, this glycosylation method was applied successfully to the total synthesis of a biologically active natural product, cholesteryl 6-O-myristoyl-α-glucoside.

Here reports an photoinduced glycosylation of trichloroacetimidate donors and several alcohols using 3,11-dimethoxydinaphthothiophene as an organo Lewis photoacid catalyst upon long-wavelength UV-LED light (385 nm) irradiation. The reaction proceeded under mild reaction conditions smoothly to give the corresponding glycosides in good to high yields. In addition, the present glycosylation method was applicable to a wide range of trichloroacetimidate donors and acceptors. Furthermore, the dinaphthothiophene catalyst could be recovered and reused without any loss of efficiency. Moreover, this glycosylation method was applied successfully to the total synthesis of a biologically active natural product, cholesteryl 6-O-myristoyl-α-glucoside.

Regio- and stereoselective formation of the 1,2-cis-furanosidic linkage has been in great demand for efficient synthesis of biologically active natural glycosides. In this study, we developed a regioselective and β-stereospecific d-/l-arabinofuranosylation promoted by a boronic acid catalyst under mild conditions. The glycosylations proceeded smoothly for a variety of diols, triols, and unprotected sugar acceptors to give the corresponding β-arabinofuranosides (β-Arbf) in high yields with complete β-stereoselectivity and high regioselectivity. The regioselectivity was completely reversed depending on the optical isomerism of the donor used and was predictable a priori using predictive models. Mechanistic studies based on DFT calculations revealed that the present glycosylation occurs through a highly dissociative concerted SNi mechanism. The usefulness of the glycosylation method was demonstrated by the chemical synthesis of trisaccharide structures of arabinogalactan fragments.

Abstract Avian pathogenic Escherichia coli O1 (APEC O1) is a pathogenic bacterium that causes significant economic losses in the poultry industry and raises concerns about zoonotic infections. The development of effective vaccines against APEC O1 is essential due to antibiotic resistance and the potential for severe symptoms in both chickens and humans. In this context, we have been focusing on the O1A, O1B, and O1C antigen structures derived from E. coli O1 lipopolysaccharide (LPS). In this study, the first synthesis of the pentasaccharide repeating units of the O1B and O1C antigens was successfully achieved. The synthesis and immunological evaluation of their conjugates with bovine serum albumin (BSA) were conducted. Only the O1A-pentasaccharide structure is a glycotope candidate for APEC O1. Keyhole limpet hemocyanin (KLH)–O1A-pentasaccharide conjugate was also synthesized, and its immunogenicity was evaluated by the ELISA assay. The efficient production of antibodies capable of binding to both APEC O1 LPS and the O1A-pentasaccharide structure was observed, indicating that O1A-pentasaccharide is a promising vaccine candidate against APEC O1.

A novel tumor-related biomarker, a H2O2-activatable photosensitizer 4 based on the 1,3-dicarbonyl enol moieties of hypocrellin B (3), was designed and synthesized. The photosensitizer 4 showed a blue-shifted absorption band compared with 3, and showed negligible photosensitizing ability without H2O2. However, the release of 3 from 4 by the reaction with H2O2 regenerated the photosensitizing ability. Furthermore, 4 exhibited selective and effective photo-cytotoxicity against high H2O2-expressing cancer cells upon photo-irradiation with 660 nm light, which is inside the phototherapeutic window.

Synthesized fucoidan derivative 10 exhibited inhibitory activities against the binding of heparin with several SARS-Cov-2 spike proteins, but did not inhibit factor Xa activity that could otherwise lead to undesirable anticoagulant activity.