Preparation of 5'-deoxy-5'-amino-5'-C-methyl adenosine derivatives and their activity against DOT1L

Abstract

From a readily available 5-C-Me ribofuranoside, we have realized a reliable route to valuable 5'-deoxy-5'-amino-5'-C-methyl adenosine derivatives at gram scale with confirmed stereochemistry. These adenosine derivatives are useful starting materials for the preparation of 5'-deoxy-5'-amino-5'-C-methyl adenosine derivatives with higher complexity. From one of the new adenosine derivatives, some 5'-deoxy-5'-amino-5'-C-methyl adenosine DOT1L inhibitors were prepared in several steps. Data from DOT1L assay indicated that additional 5'-C-Me group improved the enzyme inhibitory activity.

Keywords: 5′-Deoxy-5′-amino-5′-C-methyl adenosine derivative; DOT1L inhibitor; N-glycosylation; Nucleoside synthesis; Structure activity relationship.