Synthesis of enantiomerically pure (S)-methanocarbaribo uracil nucleoside derivatives for use as antiviral agents and P2Y receptor ligands.
We have developed an approach toward enantiomerically pure (S)-methanocarba ribonucleosides based on several functional group transformations on a sensitive bicyclo[3.1.0]hexane system. D-ribose was transformed into methanocarba alcohol 3 followed by conversion of the OH group to a nitrile with inversion of configuration at C4. The nitrile group was subsequently reduced in two stages to the 5'-hydroxymethyl group. An ester group appended to a tertiary carbon (C1) was transformed to an amino group as a nucleobase precursor.
Melman
Artem
A
Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, New York 13699, USA.
Zhong
Minghong
M
Marquez
Victor E
VE
Jacobson
Kenneth A
KA
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D008024:Ligands; D058919:Purinergic P2 Receptor Antagonists; D012266:Ribose / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014498:Uracil; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000998:Antiviral Agents; D001643:Bridged Bicyclo Compounds; D008024:Ligands; D058919:Purinergic P2 Receptor Antagonists; C046059:bicyclo(3.1.0)hexane; D014498:Uracil; D012266:Ribose; D014529:Uridine