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Solid phase synthesis of purines from pyrimidines.
R Di Lucrezia1, I H Gilbert, C D Floyd
1Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3XF U.K.
Journal of Combinatorial Chemistry
|May 29, 2000
Summary
This study details a solid-phase synthesis for substituted purines using a novel pyrimidine precursor. Key challenges in nitro group reduction were overcome, enabling diverse purine derivative generation.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Synthetic Chemistry
Background:
- Pyrimidine derivatives are crucial scaffolds in medicinal chemistry.
- Solid-phase synthesis offers advantages for combinatorial library generation.
- Efficient synthesis of substituted purines is essential for drug discovery.
Purpose of the Study:
- To describe a novel solid-phase synthesis of substituted purines.
- To overcome synthetic challenges in purine elaboration.
- To generate diverse purine analogs for potential therapeutic applications.
Main Methods:
- Solid-phase synthesis initiated with 4,6-dichloro-5-nitropyrimidine coupled to Rink amide resin.
- Nucleophilic displacement of chloride with amino compounds.
- Reduction of the nitro group using lithium aluminum hydride/aluminum trichloride.
- Elaboration of diamines to purines via three distinct synthetic routes.
Main Results:
- Successful synthesis of various substituted purines was achieved.
- A robust method for nitro group reduction under challenging conditions was established.
- Multiple routes for purine ring formation were demonstrated.
Conclusions:
- The described solid-phase approach provides a versatile platform for synthesizing substituted purines.
- The developed methodology facilitates access to diverse purine libraries.
- This synthesis strategy holds potential for accelerating the discovery of novel bioactive purine compounds.