Total Synthesis of Anti-Influenza Agents Zanamivir and Zanaphosphor via Asymmetric Aza-Henry Reaction

The
potent anti-influenza agents, zanamivir and its phosphonate
congener, are synthesized by using a nitro group as the latent amino
group at C4 for asymmetric aza-Henry reaction with a chiral sulfinylimine,
which is derived from inexpensive d-glucono-δ-lactone
to establish the essential nitrogen-containing substituent at C5.
This method provides an efficient way to construct the densely substituted
dihydropyran core of zanamivir and zanaphosphor without using the
hazardous azide reagent.