The First Synthesis and Anti‐retroviral Activity of 5′,5′‐Difluoro‐3′‐Hydroxy‐Apiosyl Nucleoside Cyclomonophosphonic Acid Analogs

Abstract

The first synthesis of novel 5′,5′‐difluoro‐3′‐hydroxy apiose nucleoside cyclomonophosphonic acid analogs was performed as potent anti‐retroviral agents. Phosphonation was performed by direct displacement of a triflate intermediate with diethyl(lithiodifluoromethyl) phosphonate to give the corresponding (α,α‐difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection of diethyl phosphonates provided the target nucleoside cyclomonophosphonic acid analogs. The synthesized nucleoside analogs were subjected to anti‐viral screening against the human immunodeficiency virus‐1 (HIV‐1). Cytosine analogs show significant anti‐HIV activity.