Nucleoside alkaloids with anti-platelet aggregation activity from the rhizomes of Ligusticum striatum

Two new (1–2) and six known (3–8) nucleoside alkaloids were isolated from the rhizomes of Ligusticum striatum DC. Compounds 1 and 2 (liguadenosines A and B) were unusual N-10 substituted adenosine derivatives. Their structures were elucidated by extensive spectroscopic analyses and ECD calculation. Most of them significantly inhibited the abnormal increase in platelet aggregation induced by ADP at concentrations of 50 and 100 μM. Particularly, the inhibitory effect of 3 was equivalent to aspirin.     

Microwave chemistry: Synthesis of purine and pyrimidine nucleosides using microwave radiation

Pyrimidine and purine nucleosides have a remarkable and comprehensive impact on medicinal chemistry and pharmaceutical industries. They become key parts of the growing interdisciplinary area of antimetabolites. The paramount importance of the nucleoside analogs triggered their broader use in treatment of critical diseases such as cancer, malignancies, microbial infection, and autoimmune diseases. Recent advances in their synthetic strategies through microwave-assisted organic synthesis (MAOS) have been reviewed.     

Synthesis of 3′-fluoro-4′-amino-hexitol nucleosides with a pyrimidine nucleobase as building blocks for oligonucleotides

The synthesis of 3′-fluoro-4′-amino-hexitol nucleosides with a uracil and cytosine nucleobase was performed. The synthesis started from 1,5:2,3-dianhydro-4,6-benzylidene-allitol and afforded the target compounds in 15 steps. These protected hexitol nucleosides are valuable building blocks for the preparation of a new class of oligonucleotides.     

Selected Thoughts on Hydrophobicity in Drug Design

The fundamental aim of drug design in research and development is to invent molecules with selective affinity towards desired disease-associated targets. At the atomic loci of binding surfaces, systematic structural variations can define affinities between drug candidates and biomolecules, and thereby guide the optimization of safety, efficacy and pharmacologic properties. Hydrophobic interaction between biomolecules and drugs is integral to binding affinity and specificity. Examples of antiviral drug discovery are discussed.     

Synthesis of Piperidine Nucleosides as Conformationally Restricted Immucillin Mimics

The de novo synthesis of piperidine nucleosides from our homologating agent 5,6-dihydro-1,4-dithiin is herein reported. The structure and conformation of nucleosides were conceived to faithfully resemble the well-known nucleoside drugs Immucillins H and A in their bioactive conformation. NMR analysis of the synthesized compounds confirmed that they adopt an iminosugar conformation bearing the nucleobases and the hydroxyl groups in the appropriate orientation.     

A solid-supported acidic oxazolium perchlorate as an easy-handling catalyst for the synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation

A solid-supported acidic oxazolium perchlorate was investigated as a heterogeneous catalyst in N-glycosylation reactions using silylated modified pyrimidines and an acylated ribose or glucose to afford the corresponding pyrimidine nucleosides. This salt is a nonhygroscopic and stable powder whose activity is comparable to that of 2-methyl-5-phenylbenzoxazolium perchlorate. A reaction with this polymer catalyst can be conducted on a gram scale. Reusability of the solid-supported catalyst was also investigated.     

NMR studies on 4‐thio‐5‐furan‐modified and 4‐thio‐5‐thiophene‐modified nucleosides

Systematic NMR characterization of 4‐thio‐5‐furan‐pyrimidine nucleosides or 4‐thio‐5‐thiophene‐pyrimidine nucleosides (ribonucleosides and 2′‐deoxynucleosides) was performed. All proton and carbon signals of 4‐thio‐5‐thiophene‐ribouridine and related analogues were unambiguously assigned. The orientations of the base (4‐thiouridine or its deoxy analogue) relative to the ring (furan or thiophene) are explored by a NMR approach and further supported by X‐ray crystallographic studies. The procedures presented here would be applicable to other modified nucleosides and nucleotides. Copyright © 2016 John Wiley & Sons, Ltd.     

An Efficient Synthesis of 2‐Substituted Benzoxazoles via RuCl3·3H2O Catalyzed Tandem Reactions in Ionic Liquid

An efficient synthesis of 2‐substituted benzoxazoles through RuCl₃·3H₂O catalyzed, air oxidized tandem reactions of 2‐aminophenols and aldehydes in [bmim]BF₄ was developed. This synthetic strategy has such advantages as mild reaction conditions, cost‐free oxidant, readily available starting materials, and recyclable catalyst and solvent. As an application, it was successfully used in the synthesis of the unreported 5‐(benzoxazol‐2‐yl)‐2′‐deoxyuridines with potential biological activities.     

Prebiotic Nucleoside Synthesis: The Selectivity of Simplicity

Ever since the discovery of nucleic acids 150 years ago,^[1] major achievements have been made in understanding and decrypting the fascinating scientific questions of the genetic code.^[2] However, the most fundamental question about the origin and the evolution of the genetic code remains a mystery. How did nature manage to build up such intriguingly complex molecules able to encode structure and function from simple building blocks? What conditions were required? How could the precursors survive the unhostile environment of early Earth? Over the past decades, promising synthetic concepts were proposed providing clarity in the field of prebiotic nucleic acid research. In this Minireview, we show the current status and various approaches to answer these fascinating questions.