High-yielding synthesis of the anti-influenza neuraminidase inhibitor (-)-oseltamivir by two 'one-pot' sequences

The efficient asymmetric total synthesis of (―)-oseltamivir, an antiviral reagent, has been accomplished by using two "one-pot" reaction sequences, with excellent overall yield (60 % ) and only one required purification by column chromatography. The first one-pot reaction sequence consists of a diphenylprolinol silyl ether mediated asymmetric Michael reaction, a domino Michael reaction/ Horner―Wadsworth―Emmons reaction combined with retro-aldol/Horner― Wadsworth―Emmons reaction and retro Michael reactions, a thiol Michael reaction, and a base-catalyzed isomerization. Six reactions can be successfully conducted in the second one-pot reaction sequence; these are deprotection of a tert-butyl ester and its conversion into an acyl chloride then an acyl azide, Curtius rearrangement, amide formation, reduction of a nitro group into an amine, and a retro Michael reaction of a thiol moiety. A column-free synthesis of (—)—oseltamivir has also been established.