2. Academic Validation
  3. Enantiomeric 4'-truncated 6'-fluoro-3-deazaneplanocin and its 3-bromo derivative: Synthesis and antiviral properties, including Ebola and Marburg

Enantiomeric 4'-truncated 6'-fluoro-3-deazaneplanocin and its 3-bromo derivative: Synthesis and antiviral properties, including Ebola and Marburg

  • Bioorg Med Chem Lett. 2021 Jun 1:41:127985. doi: 10.1016/j.bmcl.2021.127985.
Chloe Haverkamp 1,  Chong Liu 1,  Stewart W Schneller 2
Affiliations

Affiliations

  • 1 Molette Laboratory for Drug Discovery, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL, United States.
  • 2 Molette Laboratory for Drug Discovery, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL, United States. Electronic address: [email protected].
PMID: 33766766 DOI: 10.1016/j.bmcl.2021.127985
Abstract

In seeking to increase the library of fluorine containing adenine-derived carbocyclic nucleoside Antiviral candidates, d-like and l-like 6'-fluoro-3-deazaneplanocin and its 3-bromo derivative lacking the 4'-hydroxylmethylene substituent (2/3 and 4/5, respectively) are presented. Their synthesis was accomplished from d-ribose by developing a more facile precursor route than suggested by the literature. The 2/4d-like pair displayed significant anti-filo virial properties while the enantiomeric l-like congeners 3/5 were inactive. Target compounds 2/4 also were active towards measles and norovirus. The effect of 2/4 is further evidence of the role fluoro-derived adenine carbocyclic nucleoside can play in Antiviral drug discovery. Furthermore, the simplicity of their synthesis lends them to more efficacious analogs and to scale-up optimization. There were no Other relevant Antiviral properties for 2/3 and 4/5 (except BK polyomavirus for 3/5).

Keywords

3-Deazaneplanocin; Ebola; Enantiomeric carbocyclic nucleosides; Marburg; Measles; Mitsunobu reaction; Norovirus; α-Fluorocyclopentenones.

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