Ni-Catalyzed Cross-Coupling of 2-Iodoglycals and 2-Iodoribals with Grignard Reagents: A Route to 2-C-Glycosides and 2’-C-Nucleosides

Graphical Abstract

The importance of O/N-glycosides as biologically active compounds cannot be overstated. This study is focused on the functionalization of glycals and ribals at the C2 position with alkyl, vinyl, aryl, heteroaryl and strained ring substituents. The functionalized glycals and ribals were transformed into 2-C-deoxyglycosides and 2’-C-deoxynucleosides. The application to the synthesis of an analogue of cladribine and clofarabine is described.

Abstract

The synthesis of 2-C-glycals and 2-C-ribals was achieved in good yields using a nickel-catalyzed cross-coupling between 2-iodoglycals and 2-iodoribal respectively and Grignard reagents. The prepared 2-C-glycals and ribals were then transformed into 2-C-2-deoxyglycosides, 2-C-diglycosides and 2’-C-2’-deoxynucleosides. The developed method was applied to the synthesis of a 2-chloroadenine

2’-deoxyribonucleoside – a structural analogue of cladribine (Mavenclad®, Leustatin®) and clofarabine (Clolar®, Evoltra®), two compounds used in the treatment of relapsing-remitting multiple sclerosis and hairy cell leukemia.