Kinetics of Strain-Promoted Alkyne-Nitrone Cycloadditions (SPANC) with Unprotected Carbohydrate Scaffolded Nitrones
Nathan Noël1, Agathe Martinez1, Fabien Massicot1
1Université de Reims Champagne-Ardenne, CNRS UMR 7312, ICMR, 51687 Reims, France.
Organic Letters
|May 1, 2024
Summary
Unprotected carbohydrate-derived nitrones were explored for bioconjugation via strain-promoted alkyne-nitrone cycloadditions. This versatile method shows promise for applications in aqueous environments.
Area of Science:
- Organic Chemistry
- Bioconjugation Chemistry
- Carbohydrate Chemistry
Background:
- Strain-promoted alkyne-nitrone cycloaddition (SPAN) is a click chemistry reaction.
- SPAN reactions are valuable for bioconjugation due to their bioorthogonality and efficiency.
- Developing novel nitrone precursors is crucial for expanding SPAN applications.
Purpose of the Study:
- To investigate unprotected carbohydrate-derived nitrones as novel partners in SPAN reactions.
- To assess the utility of these carbohydrate-based nitrones for bioconjugation.
- To demonstrate the applicability of this method in aqueous media.
Main Methods:
- Synthesis of unprotected carbohydrate-derived nitrones.
- Strain-promoted alkyne-nitrone cycloaddition reactions with cyclooctyne.
- Kinetic analysis of the cycloaddition reactions.
- One-pot protocol development in aqueous media.
Main Results:
- Carbohydrate-derived nitrones were successfully employed in SPAN reactions.
- Second-order rate constants ranged from 3.4 × 10^-4 to 5.8 × 10^-2 M^-1 s^-1, comparable to other nitrones.
- A one-pot protocol was established for sequential nitrone formation and cycloaddition in water.
Conclusions:
- Unprotected carbohydrate-derived nitrones are effective reagents for bioconjugation via SPAN.
- This methodology offers a new tool for bioconjugation, particularly in aqueous conditions.
- The carbohydrate scaffold provides a versatile platform for developing new nitrone reagents.
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