RESUMO
Baloxavir marboxil (1; BXM) is a potent drug used for treating influenza infections. The current synthetic route to BXM (1) is based on optical resolution; however, this method results in the loss of nearly 50% of the material. This study aimed to describe an efficient and simpler method for the synthesis of BXM. We achieved a stereoselective synthesis of BXM (1). The tricyclic triazinanone core possessing a chiral center was prepared via diastereoselective cyclization utilizing the readily available amino acid l-serine. The carboxyl moiety derived from l-serine was removed via photoredox decarboxylation under mild conditions to furnish the chiral tricyclic triazinanone core ((R)-14). The synthetic route demonstrated herein provides an efficient and atomically economical method for preparing this potent anti-influenza agent.
Assuntos
Dibenzotiepinas , Serina , Estereoisomerismo , Ciclização , Serina/química , Estrutura Molecular , Dibenzotiepinas/química , Dibenzotiepinas/síntese química , Triazinas/química , Triazinas/síntese química , Oxirredução , Descarboxilação , Morfolinas/química , Morfolinas/síntese química , Piridonas/química , Piridonas/síntese química , Processos Fotoquímicos , Antivirais/síntese química , Antivirais/químicaRESUMO
The reaction of terminal alkynes with hydrosilanes and tert-alkyl isocyanides in the presence of Rh(4)(CO)(12) gives (Z)-ß-silyl-α,ß-unsaturated imines in good yields. On the other hand, the use of aryl isocyanides in place of tert-alkyl isocyanides leads to the formation of E isomers.