Rhodium catalyzed stereospecific reductive carbocyclization of 1,6-enynes and synthesis of 4'-methyl-6'-substituted aristeromycins
| Autor: | Chandralata Bal, Ramakrishnamraju Samunuri, Ashok K. Jha |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adenosine
Stereochemistry Guanosine 010402 general chemistry 01 natural sciences Biochemistry Catalysis chemistry.chemical_compound Stereospecificity Genetics medicine Humans Rhodium BINAP Molecular Structure 010405 organic chemistry Chemistry Asymmetric hydrogenation Stereoisomerism General Medicine cccDNA Entecavir 0104 chemical sciences Cyclization Alkynes Molecular Medicine Mitsunobu reaction Nucleoside Oxidation-Reduction medicine.drug |
| Zdroj: | Nucleosides, nucleotidesnucleic acids. 38(6) |
| ISSN: | 1532-2335 |
| Popis: | The need of long-term treatment for chronic HBV, emergence of drug-resistant viruses and inefficiency of currently approved therapies to eliminate covalently closed circular DNA (cccDNA), mandates identification of potent and selective inhibitors of HBV replication with novel mechanisms of action. Entecavir, a carbocyclic guanosine nucleoside analog, is the most potent inhibitor of HBV replication on the market. Moreover, the naturally occurring carbocyclic nucleosides aristeromycin are known for their wide range of antiviral activities. In this research, we have utilized BINAP directed rhodium catalyzed reductive carbocyclization of 1,6-enynes (8a-b) through asymmetric hydrogenation which is an approach, not yet explored in carbocyclic sugar synthesis. Interestingly, we obtained exclusive anti-(9a) and Z-anti (9b) carbocyclic sugars. The new aristeromycin analogs (10a-b) with scaffold combination of entecavir and aristeromycin were then synthesized using the Mitsunobu reaction followed by deprotection. |
| Databáze: | OpenAIRE |
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