A versatile method to prepare difluorinated primary alcohols and its application to the syntheses of novel acyclic fluorinated nucleosides

A four-step reaction sequence, converting general ketone precursor 1 to difluoro primary alcohol 5, has been developed. This synthetic method has been successfully applied to prepare compound 13 as the difluoro-analog of the antiviral drugs ganciclovir and penciclovir. The addition of fluorine to a...

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Bibliographic Details
Published in:Tetrahedron letters 2013-12, Vol.54 (50), p.6909-6911
Main Author: Tse, Bruno
Format: Article
Language:English
Subjects:
Alcohols
Antiviral
Drugs
Fluorination
Fluorine
Ganciclovir
Ketones
Nucleosides
Penciclovir
Radicals
Tetrahedrons
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Summary:A four-step reaction sequence, converting general ketone precursor 1 to difluoro primary alcohol 5, has been developed. This synthetic method has been successfully applied to prepare compound 13 as the difluoro-analog of the antiviral drugs ganciclovir and penciclovir. The addition of fluorine to a molecule often leads to intriguing changes in the properties of the molecule. Many novel drug leads and drug candidates are the results of the incorporation of fluorine. This Letter presents a versatile method to create molecules with the general structure R1R2CHCF2CH2OH from ketone R1(CO)R2. The key steps of this synthetic method involve the formation of a cyclic thiocarbonate and the regioselective radical opening of the thiocarbonate to yield the corresponding primary alcohol –CF2CH2OH. Using this synthetic method, novel fluorinated analogs of ganciclovir and penciclovir have been prepared.
ISSN:0040-4039
1873-3581
DOI:10.1016/j.tetlet.2013.10.037