A nitrone-based cycloaddition approach to the synthesis of the glycosyl system of nogalomycin, menogaril, and their congeners

Abstract

A series of model systems for the benzoxocin portion of nogalomycin was synthesized by cycloaddition of nitrone 8 with assorted dipolarophiles. Cycloaddition between nitrone 8 and vinyltrimethylsilane afforded isoxazolidines which were fragmented to produce either benzoxocins 21 and 23 or tricyclic isomer 27. Tricyclic systems 23 a,d 27 were produced also from the adduct of nitrone 8 and allyltrimethylsilane following fragmentation and oxidative cleavage of the resulting homoallylic amine derivative. Dipolar cycloaddition between nitrone 8 and vinylene carbonate yielded two disatereomeric isoxazolidines 40 and 41, both of which had the intact carbon skeleton of the glycosyl region of nogalomycin but which bore the incorrect relative configuration for transformation to menogaril analogue 5