Synthesis of non glycosidic nucleobase-sugar mimetics

Biologically active organic molecules acting as nucleoside mimics are frequently encountered in pharmaceutical research. They are either synthetic heterocycles, which miss the sugar-derived interactions with the active site of the nucleoside-binding protein, or natural products containing a glycosidic linkage, which may cause bioavailability and metabolic stability problems. We report here the concept of synthetic full nucleoside mimics, including both a N-containing nucleobase-like portion and a sugar-like moiety, where the latter consists of 5- and 6-membered carbacycles connected by a more stable and drug-like C-N bond to the nucleobase mimic. Compounds 14,16 (indolinones), 21 and 23 (benzimidazolones) have been prepared as model compounds. (C) 2009 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.