2-Fluorocordycepin: Chemoenzymatic Synthesis and Study of Anticancer Activities In Vitro

Abstract

Objective: The aim of this study was to develop an efficient method for the preparation of 2-fluorocordycepin and to evaluate its anticancer activity in vitro. Methods: An approach to chemical synthesis of 2-fluorocordycepin was developed. The conditions of chemoenzymatic synthesis of this compound were optimized. Results and Discussion: 2-Fluorocordycepin was prepared chemically using α-acetoxyisobutyryl bromide in three steps with 34% yield and by enzymatic method using E. coli purine nucleoside phosphorylase and 1-alpha phosphate of 3-deoxyribose with 66% yield. The latter compound was synthesized in eight steps: the protected isopropylidene derivative of 3-deoxyribose was obtained in four steps, followed by an attempt at direct “one pot” phosphorylation. Conclusions: Two methods of 2-fluorocordycepin preparation were proposed and implemented: chemical synthesis from 2-fluoradenosine and chemoenzymatic synthesis, including preparation of 3-deoxyerythropentofuranoso-1-phosphate, followed by transglycosylation using E. coli purine nucleoside phosphorylase. The cytotoxic activity of 2-fluorocordycepin in vitro was evaluated. It was shown that 2-fluorocordycepin exhibits antimetabolic effect against a number of cancer cell lines (Jurkat, Raji, MCF-7, THP-1, U937, A549, LS174T), which allows us to consider this compound as a promising candidate for the development of anticancer drugs.