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.

高效的抗流感药物扎那米韦及其磷酸酯同系物，通过利用C4位的硝基作为潜在的氨基基团，与手性亚磺酰亚胺进行非对称性的氮杂亨利反应进行合成。该亚磺酰亚胺源自廉价的D-葡萄糖酸δ-内酯，以此在C5位上建立关键的含氮取代基。此方法为扎那米韦和扎那磷酸酯的稠密取代二氢吡喃核心的构建提供了一种高效途径，且无需使用危险的叠氮化物试剂。