Synthesis of the potent influenza neuraminidase inhibitor 4-guanidino Neu5Ac2en. X-Ray molecular structure of 5-acetamido-4-amino-2,6-anhydro-3,4,5-trideoxy-D-erythro-L-gluco-nononic acid

Abstract

An efficient and high-yielding synthesis of 4-guanidino Neu5Ac2en, the potent anti-influenza A and B compound, is described. The route exploits a stereospecific introduction of the key nitrogen functionality at C-4 via an oxazoline intermediate. Three different methods for the final-step conversion of the 4-amino into 4-guanidino derivatives are described. To explore the structure–activity relationship in this region of the molecule, a series of substituted guanidino derivatives were synthesized and their activity is described.