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 CN bond to the nucleobase mimic. Compounds 14, 16 (indolinones), 21 and 23 (benzimidazolones) have been prepared as model compounds.