Synthesis and Biological Evaluation of Oseltamivir Analogues from Shikimic Acid

Abstract

New oseltamivir analogues were designed and synthesized, starting from shikimic acid. Biological evaluation against three human cancer cell lines (KB, MCF7 and Lu-1) showed that many of them exhibited cytotoxic activity. Azides 5 are more active than the corresponding amines 6. Thus, the reduction of the azide group into amine led to the loss of cytotoxicity. The compounds with a cyclohexanemethyloxy group at C-3 were more active than the other investigated compounds belonging to the same series. This cyclohexanemethyloxy group seems to be critical for the cytotoxic activity of this class of compounds. The synthetic oseltamivir analogues 6a-e had no inhibition activity, even at the concentration of 50 µM when they were evaluated for their in vitro influenza A neuraminidase inhibitory activity by an enzymatic assay.

Production and Synthetic Modifications of Shikimic Acid

“…The preparations of oseltamivir analogues have been reported in several works, and their biological properties as neuraminidase inhibitors or antitumor agents have been studied. Such analogues have been prepared either by modification of oseltamivir or via some of the synthetic intermediates previously mentioned, ,− and for this reason will not be covered in this review article.…”