An Efficient and Safe Protocol for In Situ Generation of Azides for Click Chemistry: Late-Stage Application toward Synthesis of 1,2,3-Triazole-Embedded Uridines

Arul A. Annadurai; Chiradeep Panja; Begur VasanthKumar Varun; Arvid Mathur; Amrita Roy

doi:10.1055/a-2716-8417

Synthesis, Table of Contents

Synthesis
DOI: 10.1055/a-2716-8417

Paper

An Efficient and Safe Protocol for In Situ Generation of Azides for Click Chemistry: Late-Stage Application toward Synthesis of 1,2,3-Triazole-Embedded Uridines

Authors

Arul A. Annadurai

¹Department of Chemical Synthesis, Biocon Bristol-Myers Squibb Research Center, Bangalore, India (Ringgold ID: RIN430014)
Chiradeep Panja

¹Department of Chemical Synthesis, Biocon Bristol-Myers Squibb Research Center, Bangalore, India (Ringgold ID: RIN430014)
Begur VasanthKumar Varun

¹Department of Chemical Synthesis, Biocon Bristol-Myers Squibb Research Center, Bangalore, India (Ringgold ID: RIN430014)
Arvid Mathur

²Discovery and Development Sciences, Bristol Myers Squibb, Princeton, United States (Ringgold ID: RIN3971)
Amrita Roy

¹Department of Chemical Synthesis, Biocon Bristol-Myers Squibb Research Center, Bangalore, India (Ringgold ID: RIN430014)

Abstract

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Abstract

Nucleosides with heterocyclic side chains, such as 1,2,3-triazoles, are a well-known class of biologically active molecules. In this respect, alkyne nucleosides were found to be efficient synthons for synthesizing 1,2,3-triazoles via click chemistry. Although the selective propargylation of a nucleoside is challenging, it can be achieved by careful selection of suitable hydroxy protecting groups. On the other hand, the in situ generation of azides from the corresponding amines is a safe protocol for click chemistry, but subsequent coherent reaction conditions play a crucial role in the success of 1,2,3-triazole synthesis in a nucleoside scaffold. Herein, we describe such a safe and efficient protocol for the synthesis of 1,2,3-triazole side chain-containing nucleoside scaffold by selective propargylation of uridine. This strategy afforded access to various, previously nonreported 1,2,3-triazole-containing uridine scaffolds and opens up new avenues for such late-stage modifications in other nucleosides.

Keywords

Bacterial resistance to antibiotics - Nucleoside-based drugs - Click chemistry - 1,2,3-Triazoles - In situ azide generation - Alkyne nucleosides - Nucleosides of 1,2,3-triazole scaffold of uridine

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References

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