Premium
Synthesis of Nucleosides through Direct Glycosylation of Nucleobases with 5‐ O ‐Monoprotected or 5‐Modified Ribose: Improved Protocol, Scope, and Mechanism
Author(s) -
Downey A. Michael,
Pohl Radek,
Roithová Jana,
Hocek Michal
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201604955
Subject(s) - chemistry , nucleobase , glycosylation , ribose , combinatorial chemistry , riboside , epoxide , nucleophile , glycosyl , stereochemistry , glycosyl donor , anomer , dna , biochemistry , enzyme , catalysis
Abstract Simplifying access to synthetic nucleosides is of interest due to their widespread use as biochemical or anticancer and antiviral agents. Herein, a direct stereoselective method to access an expansive range of both natural and synthetic nucleosides up to a gram scale, through direct glycosylation of nucleobases with 5‐ O ‐tritylribose and other C 5‐modified ribose derivatives, is discussed in detail. The reaction proceeds through nucleophilic epoxide ring opening of an in situ formed 1,2‐anhydrosugar (termed “anhydrose”) under modified Mitsunobu reaction conditions. The scope of the reaction in the synthesis of diverse nucleosides and other 1‐substituted riboside derivatives is described. In addition, a mechanistic insight into the formation of this key glycosyl donor intermediate is provided.