Synthesis of Enantiomerically Pure Pyrimidine Ribonucleosides Locked in the South Conformation.

Abstract

The conformation of the central five-membered ring of a nucleoside plays an important role in enzyme recognition. Bicyclo[3.1.0]hexane, also known as the methanocarba (MC), serves as a template that can mimic the locked forms of the two distinctive conformations, namely, the north and south conformations. While modified nucleosides locked in the north conformation have been actively investigated, the south counterpart remains largely unexplored because it is difficult to synthesize. Herein, we report a concise synthetic route that can provide the key amino sugar intermediate essential for the synthesis of (S)-MC ribonucleosides in a 100% stereoselective manner. Also, through the proposed synthetic approach, we report the first synthesis of enantiomerically pure (S)-MC cytidine 1. We believe our findings would greatly contribute to the field of nucleoside chemistry and provide opportunities for novel nucleoside discovery.