Natsuhisa Oka

Ribocitrin, a natural product isolated from Streptomyces neyagawaensis MF980‐CF1, consists of ( S )‐homocitric acid and a trisaccharide unit, α‐ d ‐ribofuranosyl‐(1→2)‐α‐ d ‐ribofuranosyl‐(1→3)‐ d ‐ribofuranose. Ribocitrin exhibits inhibitory activity against Streptococcus mutans dextransucrase and is therefore considered a potential preventive agent for dental caries. Although ribocitrin exhibits promising biological activity, its structural complexity is anticipated to render chemical synthesis difficult; accordingly, neither the trisaccharide moiety nor the full molecule has been synthesized to date. In this study, we present the first successful synthesis of the trisaccharide framework of ribocitrin via 1,2‐ cis ‐α‐selective ribofuranosylation using ribofuranosyl iodides as glycosyl donors. Both α‐glycosidic linkages were constructed with complete 1,2‐ cis ‐selectivity. The trisaccharide structure was confirmed by comparison of the spectroscopic data of its per‐ O ‐acetylated derivative with those previously reported.

Glycosylated self-assembling molecules enable the construction of nanostructures whose surfaces are decorated with saccharides under aqueous conditions, reminiscent of biological systems at both the molecular and cellular levels. Such glyco-nanostructures thus hold great promise as soft materials for biological applications. Herein, we report the facile synthesis of glycosylated diarylmethyloxy-triazines, which serve as new building blocks for fabricating self-assembled nanostructures in aqueous media and forming supramolecular hydrogels. The triazine scaffold enables the protecting-group-free synthesis of glycosylated compounds with reasonable β-anomer selectivity. Notably, both the substituents on the aryl groups attached to the triazine core and the geometry of the glycosidic linkages in the disaccharides strongly influence the hydrogelation behavior.

Glycosylated self-assembling molecules enable the construction ofnanostructures whose surfaces are decorated with saccharides under aqueous conditions, reminiscent ofbiological systems at both the molecular and cellular levels. Such glyco-nanostructures thus hold great promise as soft materials for biological applications. Herein, we report the facile synthesis ofglycosylated diarylmethyloxy-triazines, which serve as new building blocks for fabricating self-assembled nanostructures in aqueous media and forming supramolecular hydrogels. The triazine scaffold enables the protecting-group-free synthesis ofglycosylated compounds with reasonable β-anomer selectivity. Notably, both the substituents on the aryl groups attached to the triazine core and the geometry of the glycosidic linkages in the disaccharides strongly influence the hydrogelation behavior and morphology ofthe self-assembled nanostructures.

Malaria research is facing a concerning challenge due to the continuously increasing number of cases and deaths, along with the Plasmodium parasite's resistance against first-line treatments, emphasising the need for novel effective antimalarials.

Nucleoside analogs play an important role in antiviral therapy because they mimic natural nucleosides and disrupt viral genome replication. Hepatitis C virus (HCV), a positive-sense single-stranded RNA virus, remains a major global health concern. Viral replication depends on the RNA-dependent RNA polymerase NS5B, making it an important target for antiviral drug development. Modification of uridine at the C5 position has been reported to enhance antiviral potency, metabolic stability, and resistance profiles. In this study, a series of 5-isoxazolyl-substituted uridine derivatives was designed and evaluated using an integrated in silico approach. Molecular docking was performed to investigate binding modes and affinities toward wild-type HCV NS5B genotype 1a and the drug-resistant genotype 1b N316 variant. Molecular dynamics (MD) simulations were conducted to examine the stability and dynamic behavior of the protein–ligand complexes. In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were predicted to assess pharmacokinetic and safety profiles. Docking results suggested that C5 modification enhances binding affinity compared with the reference drug sofosbuvir. Among the designed analogs, compound 7 bearing a 3-(4-pyridyl)isoxazolyl group exhibited the most favorable binding free energies against both targets. Mechanistic analysis suggested that this substituent enhances hydrophobic interactions within the wild-type binding pocket while forming a compensatory hydrogen bond with the mutated Asn316 residue. MD simulations confirmed the stability of the compound 7–NS5B complexes, and ADMET predictions indicated favorable pharmacokinetic properties. These findings suggest that the 5-(3-(4-pyridyl)isoxazolyl)uridine scaffold represents a promising framework for developing next-generation HCV NS5B inhibitors.

tert-Butyl (diphenylphosphono)bromoacetate 3d was readily prepared by brominating tert-butyl diphenylphosphonoacetate 5d. The HWE reaction of 3d with various aldehydes gave (E)-α-bromoacrylates 1 with selectivity ranging from 89:11 to 99:1, typically in yields exceeding 90%. Additionally, the HWE reactions after treatment of 3d with NaI or iodinating 5d produced the corresponding (E)-α-iodoacrylates 7 in yields of 87-100%, with selectivities ranging from 91:9 to 99:1. The products were used to synthesize trisubstituted alkenes through Sonogashira coupling.