Synthesis of a novel carbocyclic analog of bredinin
1Center for Drug Discovery and College of Pharmacy, University of Georgia, Athens, GA 30602, USA. vnair@rx.uga.edu.
Abstract:
The natural nucleoside antibiotic, bredinin, exhibits antiviral and other biological activities. While various nucleosides related to bredinin have been synthesized, its carbocyclic analog has remained unknown. Synthesis of this heretofore unknown analog of bredinin is described. The key precursor, (3aS,4R,6R,6aR)-6-((methoxy-methoxy)methyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-amine (5), was prepared from the commercially available compound, (1R,4S)-2-azabicyclo[2.2.1] hept-5-en-3-one (4). Our initial approach used intermediate 6, derived in three transformations from 5, for the key photolytic step to produce the desired ring-opened precursor to the target compound. This photochemical transformation was unsuccessful. However, an appropriately protected and related precursor was synthesized from 5 through the following side-chain functional group transformations: elaboration of the amino group through malonyl ester formation, oximation at the central carbon, conversion of ester to amide and catalytic reduction of the oxime group. This precursor, on treatment with triethylorthoformate and catalytic acetic acid in ethanol, underwent cyclization to produce the desired 4-carbamoyl-imidazolium-5-olate ring. Deprotection of the latter product proceeded smoothly to give the carbocyclic analog of bredinin. This target molecule exhibits antiviral activity, albeit low, against a number of RNA viruses. Further biological evaluations are in progress.
Related Concept Videos
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
β-Dicarbonyl Compounds via Crossed Claisen Condensations
Inhibitors of Bacterial DNA Synthesis
Insulin: Biosynthesis, Chemistry, and Preparation
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
Inhibitors of Bacterial Protein Synthesis


