Unifying the synthesis of nucleoside analogs

Nucleosides, the building blocks of DNA and RNA, typically contain a ribose sugar attached to a nucleobase. Structurally modified nucleoside analogs can disrupt the biological processes that mediate nucleoside assembly into DNA and RNA. Nucleoside analogs that target viral and cell replication have delivered generations of drugs combatting cancer, herpes simplex virus, human immunodeficiency virus, and hepatitis C virus (1–4). Despite these successes, considerable challenges remain in chemically synthesizing nucleoside analogs, especially the development of short and general synthetic routes. On page 725 of this issue, Meanwell et al. (5) report a rapid and scalable de novo synthesis of a diverse range of nucleoside analogs from simple achiral starting materials. Their approach builds on previous work by Peifer et al. (6), who introduced a facile and enantioselective synthetic approach to pentose sugars.