Synthesis of naphthyridone derivatives containing 8-alkoxyimino-1,6-dizaspiro[3.4]octane scaffolds

The synthesis of naphthyridone derivatives containing 8-alkoxyimino-1,6-dizaspiro[3.4]octane scaffolds, the position isomers of the side chain at the C-7 position of Zabofloxacin, has been achieved in eight steps from tert-butyl 3-cyano-4-oxopyrrolidine-1-carboxylate. The possible reaction mechanisms were also proposed. The key spirocyclic carbamate esters, which could be prepared using a modified Hofmann rearrangement strategy, were condensed with naphthyridone nuclei, and the resulting condensates were easily cleaved by TMSI and subsequently cyclized in the presence of K2CO3. Moreover, additional N-methylation derivatives were also obtained using the synthetic sequence.

Graphical abstractA novel series of naphthyridone derivatives containing 8-alkoxyimino-1,6-dizaspiro[3.4]octane scaffolds were designed and synthesized. The synthetic methods were investigated and the mechanisms were postulated.Download full-size image