Presentation Title

A Stereocontrolled Synthesis of Xylo- and Arabinofuranoside Analogs

Start Date

November 2016

End Date

November 2016

Location

Surge 173

Type of Presentation

Oral Talk

Abstract

Several nucleoside analogs have been approved by the FDA for cytotoxic therapy and for treatment of hepatitis, HIV, and HSV. 3'-azidothymidine (AZT) was the first antiretroviral treatment for HIV and is also used to treat several human cancers. A challenging step in the synthesis of nucleoside analogs is to convert either or both of the 2' and 3'-hydroxyl groups on the ribose moiety into desired modifications with retention of configuration. Herein, we report an efficient, two-step approach to achieve desired diastereomeric configuration of the 2'/3'-hydroxyl moieties using an enantioselective reducing catalyst. Oxidation followed by enantioselective reduction provided an efficient route toward the synthesis of target molecules. This method produced the desired xylo- and arabino- configurations among both purines and pyrimidines, including adenosine, cytidine, and uridine derivatives, with up to 98% diastereomeric excess (de). The resulting nucleoside xylofuranoside derivatives were further modified by nucleophilic addition of N3 to elicit ribonucleoside guanidine (RNG) precursors. This approach may increase efficiency in the generation of nucleoside precursors of interest along with the production of xylo- and arabinofuranoside prodrugs such as cytarabine and vidarabine.

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Nov 12th, 2:45 PM Nov 12th, 3:00 PM

A Stereocontrolled Synthesis of Xylo- and Arabinofuranoside Analogs

Surge 173

Several nucleoside analogs have been approved by the FDA for cytotoxic therapy and for treatment of hepatitis, HIV, and HSV. 3'-azidothymidine (AZT) was the first antiretroviral treatment for HIV and is also used to treat several human cancers. A challenging step in the synthesis of nucleoside analogs is to convert either or both of the 2' and 3'-hydroxyl groups on the ribose moiety into desired modifications with retention of configuration. Herein, we report an efficient, two-step approach to achieve desired diastereomeric configuration of the 2'/3'-hydroxyl moieties using an enantioselective reducing catalyst. Oxidation followed by enantioselective reduction provided an efficient route toward the synthesis of target molecules. This method produced the desired xylo- and arabino- configurations among both purines and pyrimidines, including adenosine, cytidine, and uridine derivatives, with up to 98% diastereomeric excess (de). The resulting nucleoside xylofuranoside derivatives were further modified by nucleophilic addition of N3 to elicit ribonucleoside guanidine (RNG) precursors. This approach may increase efficiency in the generation of nucleoside precursors of interest along with the production of xylo- and arabinofuranoside prodrugs such as cytarabine and vidarabine.