Development of New Radical Reactions with a Vinylsilyl Group and Their Application to the Synthesis of Branched-Chain Sugar Nucleosides

Abstract

Among biologically active branched-chain sugar nucleosides, 1-(2-deoxy-2-methylene-β-D-erythro-pentofuranosyl)cytosine (DMDC), 1-(2-C-cyano-2-deoxy-β-D-arabino-pentofuranosyl)cytosine (CNDAC), and 1-(3-C-ethynyl- β-D-ribo-pentofuranosyl)cytosine (ECyd) were found to be potent antitumor antimetabolites, which significantly inhibit the growth of various human solid tumor cells both in vitro and in vivo. However, examples of synthesis of 1'- and 4'-branched-chain sugar nucleosides are rare, and because of the lack of efficient synthetic methods for their preparation, the biological activities of 1'- and 4'-branched-chain sugar nucleosides have not been systematically studied. This chapter focuses on studies that tried to develop new efficient methods for preparing such branched-chain sugar nucleosides. A radical cyclization reaction has been known as a highly versatile method for forming C-C bonds. Silicon-containing groups are very useful for the regio- and stereoselective introduction of a carbon substituent based on a temporary silicon connection and there is a growing interest in their use in intramolecular radical cyclization reactions. The chapter describes recent progress in the evaluation of new types of radical cyclization reactions and their application to the synthesis of modified nucleosides branched at 1'-, 2'-, and 4'-positions.