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Published on: November 9, 2019
Multiple multicomponent macrocyclizations including bifunctional building blocks (MiBs) based on Staudinger and
Fredy Leon1, Daniel G Rivera, Ludger A Wessjohann
1Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle/Saale, Germany.
This study expands macrocyclization methods beyond Ugi reactions, successfully synthesizing complex macrocycles using Staudinger and Passerini reactions with bifunctional building blocks.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Macrocyclic Chemistry
Background:
- Multicomponent macrocyclizations often rely on the Ugi reaction.
- Expansion to non-Ugi based methods is crucial for broader synthetic utility.
Purpose of the Study:
- To develop and exemplify efficient non-Ugi multicomponent macrocyclizations.
- To synthesize novel tetra-beta-lactam and bis-alpha-acyloxy carboxamide macrocycles.
Main Methods:
- Utilized Staudinger and Passerini three-component reactions (3CR).
- Adapted a recent oxidative variation of the Passerini-3CR involving primary alcohols, isocyanides, and carboxylic acids.
Main Results:
- Successfully synthesized tetra-beta-lactam macrocycles via Staudinger 3CR.
- Successfully synthesized bis-alpha-acyloxy carboxamide macrocycles via Passerini 3CR.
- Demonstrated the utility of non-Ugi MiBs in macrocyclization.
Conclusions:
- Established efficient non-Ugi multicomponent macrocyclization strategies.
- Expanded the scope of accessible macrocyclic structures.
- Highlighted the versatility of Staudinger and Passerini reactions in complex molecule synthesis.
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