Facile Access to Bromonucleosides Using Sodium Monobromoisocyanurate (SMBI)

Jyotirmoy Maity1, Smriti Srivastava1, Yogesh S. Sanghvi2, Ashok K. Prasad1, Roger Stromberg3

1 Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi, 2 Rasayan Inc., Encinitas, California, 3 Department of Biosciences and Nutrition, Karolinska Institutet, Novum
Publication Name:  Current Protocols in Nucleic Acid Chemistry
Unit Number:  Unit 1.39
DOI:  10.1002/cpnc.24
Online Posting Date:  March, 2017
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Abstract

Bromonucleosides constitute a significant class of molecules and are well known for their biological activity. 5‐Bromouridine, 5‐bromo‐2′‐deoxyuridine, 5‐bromouridine‐5′‐triphosphate, and nucleotides containing 5‐bromouridine have been tested and used for numerous biological studies. 8‐Bromopurine nucleosides have been used as essential precursors for the synthesis of nucleosides with fluorescent properties. This unit describes protocols for the synthesis of bromonucleosides using sodium monobromoisocyanurate (SMBI) in a straightforward way. Reactions are carried out at room temperature, and aqueous solvent mixtures are used to dissolve the nucleosides. Sodium azide is used as catalyst for the bromination of pyrimidine nucleosides, and no catalyst is necessary for the bromination of purine nucleosides. Unprotected 2′‐deoxy pyrimidine and 2′‐deoxy purine nucleosides are treated with SMBI to afford C‐5 bromo pyrimidine and C‐8 bromo purine nucleosides, respectively. This methodology has been found to be efficient for the synthesis of bromonucleosides on gram scale with consistently high yields. © 2017 by John Wiley & Sons, Inc.

Keywords: sodium monobromoisocyanurate; SMBI; bromination; bromonucleosides

     
 
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Table of Contents

  • Introduction
  • Basic Protocol 1: Synthesis of 5‐Bromopyrimidine Nucleosides
  • Basic Protocol 2: Synthesis of 8‐Bromopurine Nucleosides
  • Commentary
  • Literature Cited
  • Figures
     
 
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Materials

Basic Protocol 1: Synthesis of 5‐Bromopyrimidine Nucleosides

  Materials
  • Solvent mixture: acetonitrile:water (9:1)
  • Nucleosides:
    • 2′‐Deoxyuridine (1)
    • 2′‐Deoxycytidine (3)
  • Sodium azide
  • Sodium monobromoisocyanurate (SMBI)
  • Chloroform
  • Hexane
  • 500‐mL round‐bottom flasks
  • Magnetic stir bars and plate
  • Filtration system
  • Rotary evaporator equipped with water condenser
  • Additional reagents and equipment for thin layer chromatography (TLC; appendix 3D; Meyers and Meyers, ), 1H‐NMR and 13C‐NMR (unit 7.2; James, ), and high‐resolution mass spectrometry (HRMS; unit 10.2; Castleberry et al., )

Basic Protocol 2: Synthesis of 8‐Bromopurine Nucleosides

  Materials
  • Solvent mixture: dimethyl formamide (DMF):water (4:1)
  • Nucleosides:
    • 2′‐Deoxyadenosine (5)
    • 2′‐Deoxyguanosine (7)
  • Sodium monobromoisocyanurate (SMBI)
  • Toluene
  • Hexane
  • Methanol
  • Charcoal
  • 250‐mL and 500‐mL round‐bottom flasks
  • Magnetic stir bars and plate
  • Filtration system
  • Rotary evaporator equipped with water condenser
  • Additional reagents and equipment for thin layer chromatography (TLC; appendix 3D; Meyers and Meyers, ), 1H‐NMR and 13C‐NMR (unit 7.2; James, ), and high‐resolution mass spectrometry (HRMS; unit 10.2; Castleberry et al., )
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Figures

Videos

Literature Cited

Literature Cited
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