Stereoselective synthesis of 1-deoxy-1-ethynyl-β-d-ribofuranose as a versatile scaffold

Kitamura, Yoshiaki; Edayoshi, Kana; Kitade, Yukio

doi:10.1016/j.tetlet.2012.10.053

Cited by 8 publications

(2 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The synthesis of β‐alkynylribosides was developed in six steps from precursor 26 with 28% overall yield, as Scheme 6 shows. [ 46 ] In this sequence, the use of a β‐directing group, such as benzoyl, yield the intermediate 27 with the β‐cyano group as the sole anomer. The triple bond is obtained using the Bestmann–Ohira reagent on the aldehyde derived from the diisobutylaluminium hydride mediating the reduction of methyl ester 28 .…”

Section: Chemistrymentioning

confidence: 99%

Developments in the chemistry and biology of 1,2,3‐triazolyl‐C‐nucleosides

Nascimento,

Ferry,

Gallier

et al. 2023

Archiv der Pharmazie

View full text Add to dashboard Cite

In the last 50 years, nucleoside analogs have been introduced to drug therapy as antivirals for different types of cancer due to their interference in cellular proliferation. Among the first line of nucleoside treatment drugs, ribavirin (RBV) is a synthetic N‐nucleoside with a 1,2,4‐triazole moiety that acts as a broad‐spectrum antiviral. It is on the World Health Organization (WHO) list of essential medicines. However, this important drug therapy causes several side effects due to its nonspecific mechanism of action. There is thus a need for a continuous study of its scaffold. A particular approach consists of connecting d‐ribose to the nitrogen‐containing base with a C–C bond. It provides more stability against enzymatic action and a better pharmacologic profile. The coronavirus disease (COVID) pandemic has increased the need for more solutions for the treatment of viral infections. Among these solutions, remdesivir, the first C‐nucleoside, has been approved by the Food and Drug Administration (FDA) for clinical use against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It drew attention to the study of the C‐nucleoside scaffold. Different C‐nucleoside patterns have been synthesized over the years. They show many important activities against viruses and cancer cell lines. 1,2,3‐Triazolyl‐C‐nucleoside derivatives are a prolific and efficient subclass of RBV analogs close to the already‐known RBV with a C–C bond modification. These compounds are often prepared by alkynylation of the d‐ribose ring followed by azide‐alkyne cycloaddition. They are reported to be active against the Crimean‐Congo hemorrhagic fever virus and several tumoral cell lines, showing promising biological potential. In this review, we explore such approaches to 1,2,3‐triazolyl‐C‐nucleosides and their evolution over the years.

show abstract

Section: Chemistrymentioning

confidence: 99%

Developments in the chemistry and biology of 1,2,3‐triazolyl‐C‐nucleosides

Nascimento,

Ferry,

Gallier

et al. 2023

Archiv der Pharmazie

View full text Add to dashboard Cite

show abstract

“…In our previous studies, we have succeeded in developing versatile terminal alkyne probes and rapid ligand-free CuAAC. [10][11][12] In addition, we discovered terminal alkyne substrate-bearing heteroatoms such as oxygen and nitrogen atoms adjacent to the alkynes efficiently react with benzyl azide derivatives under CuAAC conditions to afford the corresponding triazole products. 13) Furthermore, the 1-hydroxyl group can also be utilized as a connection point with a tag for high-throughput synthesis and screening using DNA-encoded chemical libraries 14) and on-chip combinatorial libraries.…”

Section: Introductionmentioning

confidence: 99%

A Diversifiable Synthetic Platform for the Discovery of New Carbasugar SGLT2 Inhibitors Using Azide–Alkyne Click Chemistry

Kitamura

Kandeel

Oba

et al. 2023

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are clinically available to control blood glucose levels in diabetic patients via an insulin-independent mechanism. It was found that some carbasugar analogs of known SGLT2 inhibitors exert a high inhibiting ability toward SGLT2 and have a prolonged blood glucose lowering effect. In this study, we designed new candidates of carbasugar SGLT2 inhibitor that can be synthesized using copper-catalyzed azide-alkyne cycloaddition (CuAAC) into an aromatic ring, which is a part of the pharmacophore at the final stage in the synthetic protocol for the easier discovery of superior SGLT2 inhibitors. Based on the results of molecular docking studies, some selected compounds have been synthesized. Evaluation of these compounds using a cell-based assay revealed that the majority of these compounds had SGLT2 inhibitory activity in a dose-dependent manner. The SGLT2 inhibitory activity of 7b and 7c was almost equal to that of SGLT2 inhibitors in current use. Furthermore, molecular dynamics simulations also revealed that 7c is a promising novel SGLT2 inhibitor.

show abstract