A new route toward 2-acetamido-4-O-methyl-2-deoxy-d-mannopyranose from a Ferrier derivative of tri-O-acetyl-d-glucal, which contributes to aldolase-catalyzed synthesis of laninamivir (CS-8958)

A new route toward 2-acetamido-4-O-methyl-2-deoxy-d-mannopyranose (4-O-methylManNAc), the chemo-enzymatic precursor of 7-O-methylsialic acid and laninamivir, was established. Known p-methoxyphenyl 6-O-(tert-butyldimethylsilyl)-2,3-dideoxy-α-d-erythro-hex-2-enopyranoside was the starting material, and it was derived via Ferrier reaction from tri-O-acetyl-d-glucal. The total yield was 43% over six steps from the starting material. As the key steps, Payne oxidation provided a syn-epoxy alcohol, and the inversion from an aziridine to an oxazoline proceeded stereoselectively. Although the ring opening reaction of the epoxide with an azide gave both the 2- and 3-azido regioisomers, they could be merged into the desired aziridine via independent routes.