Stereocontrolled Synthesis of Aryl C-Nucleosides under Ambient Conditions

Abstract

A stereocontrolled synthesis of an aryl C-nucleoside has been developed using D-ribals and arylboronic acids catalyzed by palladium without additional ligands in common solvents under an open-air atmosphere at room temperature. This protocol features very mild conditions, simplicity in operation, exclusive βstereoselectivity, broad substrate scopes, and good compatibility with reactive amino and hydroxyl groups. The functionalization of unsaturated C-nucleosides and the late-stage glycosylation of natural products/drugs demonstrated the high practicality of this strategy.C-Nucleoside is an uncommon type of nucleoside, in which the ribofuranosyl unit is linked to the (hetero)aryl aglycone by C− C glycosidic bonds instead of C−N bonds in DNA/RNA. 1 As C−C bonds are more stable to chemical hydrolysis and enzymatic degradation than the natural C−N bonds, Cnucleosides play an important role in drug development. 2 As shown in Scheme 1a, showdomycin, a natural product isolated from Streptomyces showdoensis, demonstrates high antibacterial and anticancer bioactivities. 3 Gilvocarcin V generated by

Palladium-Catalyzed O-Glycosylation through π–π Interactions

“…However, quinoline, as an aryl ring, can also form π–π stacking interaction with another aryl ring, which was not well-developed . In continuation of our long-held interest in developing effective glycosylation methods, herein, we design a 3- O -quinaldoyl glycal donor (Scheme d), which enables the stereodivergent synthesis of α- and β- O -glycosides catalyzed by Pd species at 60 and 110 °C respectively involving π–π interactions.…”