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Molecules 2013, 18(9), 11576-11585; doi:10.3390/molecules180911576
Article

Synthesis of a Novel Carbocyclic Analog of Bredinin

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Received: 23 August 2013; in revised form: 5 September 2013 / Accepted: 10 September 2013 / Published: 17 September 2013
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
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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.
Keywords: bredinin; carbocyclic analog; synthesis; intramolecular cyclization; antiviral activity bredinin; carbocyclic analog; synthesis; intramolecular cyclization; antiviral activity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Nair, V.; Zhang, F. Synthesis of a Novel Carbocyclic Analog of Bredinin. Molecules 2013, 18, 11576-11585.

AMA Style

Nair V, Zhang F. Synthesis of a Novel Carbocyclic Analog of Bredinin. Molecules. 2013; 18(9):11576-11585.

Chicago/Turabian Style

Nair, Vasu; Zhang, Fan. 2013. "Synthesis of a Novel Carbocyclic Analog of Bredinin." Molecules 18, no. 9: 11576-11585.


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