RESUMO
Enantio- and diastereoselective synthesis of multifunctional spiropyrazolone scaffolds has been achieved using secondary amine-catalyzed [4 + 2] annulations of α,ß,γ,δ-unsaturated pyrazolones with aldehydes. The pyrazolone substrates serve as C4 synthons to produce 6-membered, carbocycle-based, chiral spiropyrazolone derivatives. The synthesized chiral compounds showed potent toxicity against a panel of cancer cell lines. The most potent compound 3h-induced cell cycle arrest and macroautophagy in HCT116 colorectal cancer cells, triggering autophagy-dependent apoptotic cell death.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoproteínas/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Pirazolonas/síntese química , Linhagem Celular Tumoral , Humanos , Estrutura MolecularRESUMO
Protecting group-controlled annulations of tetra-substituted oxindole olefins and sulfur ylides have been achieved for the synthesis of multifunctional cyclopropane- and dihydrofuran-fused spirooxindoles. Under precise annulation regulation, a variety of cyclopropane- and dihydrofuran-fused spirooxindoles containing vicinal quaternary carbon centers were produced in up to 90% yield with up to 20 : 1 dr. This reaction demonstrates high regio-, chemo- and diastereoselectivity, broad functional group tolerance and gram-scale capacity.
RESUMO
An efficient organocatalytic cascade reaction has been developed involving a Michael-hemiaminalization relay for the asymmetric synthesis of spiropiperidinone derivatives bearing adjacent quaternary and tertiary chiral centers via LUMO or HOMO activation. Importantly, this methodology demonstrates that applying distinct activation modes to different substrates in the same reaction can diverge diastereoselectivity. To our knowledge, this is also one of the few published cases of primary amine catalytic [3 + 3] cycloaddition reactions involving α-branched ß-ketoamides.
