Synthesis of O-Nicotinoyl-Substituted Depot Forms of Biologically Active N6-Benzyladenosine Analogs

Abstract

This unit describes an effective method for the preparation of N⁶-benzyl-2′,3′,5′-tri-O-nicotinoyl adenosine and N⁶-(3-fluorobenzyl)-2′,3′,5′-tri-O-nicotinoyl adenosine. These compounds are depot forms of biologically active N⁶-benzyladenosine (BAR) and its fluorinated analog N⁶-(3-fluorobenzyl)adenosine (FBAR), which had previously shown pronounced antiviral activity against human enterovirus EV-A71. BAR and FBAR bearing biodegradable O-nicotinoyl ester moieties were obtained by a three-step synthesis starting from inosine. An attractive feature of this strategy is the possibility of obtaining biodegradable depot forms of various biologically active ribonucleoside derivatives, particularly N⁶-substituted adenosine derivatives. © 2025 Wiley Periodicals LLC.

Basic Protocol: Preparation of N⁶-benzyl-2′,3′,5′-tri-O-nicotinoyl adenosine (4a).

Alternate Protocol: Preparation of N⁶-(3-fluorobenzyl)-2′,3′,5′-tri-O-nicotinoyl adenosine (4b).