An Efficient Synthesis of 5‐Aminopropargyl‐Pyrimidine‐5′‐O‐Triphosphates Through Palladium‐Catalyzed Sonogashira Coupling. Issue 1 (18th March 2019)

• Record Type: Journal Article
• Authors: Shanmugasundaram, Muthian; Senthilvelan, Annamalai; Kore, Anilkumar R.
• Editors: Beaucage, Serge L.; Bergstrom, Donald E.; Herdewijn, Piet; Matsuda, Akira
• Is Part Of: Current protocols in nucleic acid chemistry. Volume 77:Issue 1(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-03-18
• Subjects: aminopropargyl nucleotides -- cDNA microarrays -- gene expression -- labeling -- PCR -- pyrimidine -- reverse transcription; Nucleic acids -- Laboratory manuals; Nucleic Acids -- chemical synthesis; Nucleic acids; Laboratory Manuals; Electronic books; Laboratory manuals; 572.8028
• DOI: 10.1002/cpnc.81
• Languages: English
• ISSNs: 1934-9270

Abstract

Abstract: The utilization of 5‐aminopropargyl nucleotide serves as a versatile molecular biology tool for the introduction of functional groups into a nucleic acid target of interest by using in‐vitro enzymatic incorporation method. This article describes a simple, reliable, general, and efficient two‐step chemical method for the synthesis of 5‐(3‐aminopropargyl)‐2′‐deoxycytidine‐5′‐ O ‐triphosphate, 5‐(3‐aminopropargyl)‐cytidine‐5′‐ O ‐triphosphate, 5‐(3‐aminopropargyl)‐2′‐deoxyuridine‐5′‐ O ‐triphosphate, and 5‐(3‐aminopropargyl)‐uridine‐5′‐ O ‐triphosphate, starting from the corresponding pyrimidine triphosphate. The first step involves regioselective C ‐5 iodination of pyrimidine triphosphate using N‐iodosuccinimide and sodium azide. In the second step, propargylamine is coupled to the iodo‐pyrimidine using the palladium‐catalyzed Sonogashira reaction, producing good yields of highly pure (>99.5% HPLC) 5‐aminopropargyl‐pyrimidine‐5′‐ O ‐triphosphate. In this approach, the palladium‐catalyzed Sonogashira coupling reaction is highly chemoselective and does not involve protection and deprotection. © 2019 by John Wiley & Sons, Inc.