An efficient protocol for the 4β‐acylamidation of the N‐acylated glycals of Neu5Ac by using the corresponding N‐perfluoroacylated congeners as key tools has been developed and applied to the synthesis of glycals combining the features of the molecules with antiviral properties.

Two simple and rapid procedures affording 4β‐acylamido‐ and 4β‐acetoxyneuraminic acid glycals acylated or perfluoroacylated at the 5‐amino group are reported. The first protocol avoids the formation of oxazolines to synthesize the 4β‐acetamido glycals through the Ritter reaction. The second passes through the oxazoline derivative to prepare 4β‐acetoxyneuraminic acid glycals. Both protocols start from peracetylated methyl neuraminate, acylated at the amino group with a normal, a glycolyl, or a perfluoroacyl group, or with the corresponding peracetylated glycal methyl esters (of the DANA or FANA series).

A simple protocol for the synthesis of N-perfluoroacylated and N-acylated glycals of neuraminic acid, with a secondary cyclic amine (morpholine or piperidine) at the 4α position, has been set-up, starting from peracetylated N-acetylneuraminic acid methyl ester that undergoes, sequentially to its direct N-transacylation followed by a C-4 amination, a β-elimination, and a selective hydrolysis of the ester functions, without affecting the sensitive perfluorinated amide.

A protocol for direct access to C‐4‐functionalized Neu5Ac2en derivatives by allylic substitution of an α‐acetoxy group with various nucleophiles is reported. The DANA acetamido group is exchanged for a trifluoroacetylamido group (as in FANA) to avoid the formation of a stable 4,5‐oxazoline. With thiols, the reaction involves an initial attack at the anomeric carbon (Ferrier reaction) under kinetic control, followed by an equilibration of the nucleophile to the thermodynamically more stable 4‐position.

No abstract