RESUMO
Herein we report a highly efficient method for nickel-catalyzed C-N bond formation between sulfonamides and aryl electrophiles. This technology provides generic access to a broad range of N-aryl and N-heteroaryl sulfonamide motifs, which are widely represented in drug discovery. Initial mechanistic studies suggest an energy-transfer mechanism wherein C-N bond reductive elimination occurs from a triplet excited NiII complex. Late-stage sulfonamidation in the synthesis of a pharmacologically relevant structure is also demonstrated.
Assuntos
Halogênios/química , Compostos Heterocíclicos/química , Níquel/química , Fármacos Fotossensibilizantes/química , Sulfonamidas/química , CatáliseRESUMO
A method for the decarboxylative macrocyclization of peptides bearing N-terminal Michael acceptors has been developed. This synthetic method enables the efficient synthesis of cyclic peptides containing γ-amino acids and is tolerant of functionalities present in both natural and non-proteinogenic amino acids. Linear precursors ranging from 3 to 15 amino acids cyclize effectively under this photoredox method. To demonstrate the preparative utility of this method in the context of bioactive molecules, we synthesized COR-005, a somatostatin analogue that is currently in clinical trials.
Assuntos
Peptídeos/síntese química , Catálise , Ciclização , Descarboxilação , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Estrutura Molecular , Oxirredução , Peptídeos/química , Processos FotoquímicosRESUMO
Decarboxylative cross-coupling of alkyl carboxylic acids with vinyl halides has been accomplished through the synergistic merger of photoredox and nickel catalysis. This new methodology has been successfully applied to a variety of α-oxy and α-amino acids, as well as simple hydrocarbon-substituted acids. Diverse vinyl iodides and bromides give rise to vinylation products in high efficiency under mild, operationally simple reaction conditions.
Assuntos
Ácidos Carboxílicos/química , Níquel/química , Processos Fotoquímicos , Compostos de Vinila/química , Catálise , OxirreduçãoRESUMO
An advanced intermediate in a projected synthesis of pactamycin has been prepared. Early installation of the C1-dimethylurea functionality allows for its participation in a diastereoselective, chelation-controlled addition of organometal nucleophiles to the C5 prochiral ketone. Four of the molecule's six stereocenters are set with a ketone functional handle provided for subsequent manipulation.