RESUMO
Amide bond formation is one of the most executed reactions in chemistry and biology. This is largely due to the ubiquity of the amide functional group in biological molecules, natural products and pharmaceutically important drugs. We report here the development of "SuFExAmide": a new sulfur-fluoride exchange (SuFEx) click chemistry based protocol for the efficient amidation of carboxylic acids via acyl fluoride intermediates. We have developed benzene-1,3-disulfonyl fluoride as a cost effective, powerful and versatile coupling agent, which delivers challenging secondary and tertiary amides in excellent yields from sterically hindered and electron-deficient amines. The straightforward method offers significant benefits over existing protocols in terms of substrate scope, efficiency and ease of operation and is demonstrated by the synthesis of 44 amides, including GNF6702, an antiprotozoal drug candidate. In the majority of cases, the amide products are obtained in high yield without the need for excess reagents or chromatographic purification.
RESUMO
We present a selection of elegant and diverse biomimetic syntheses of complex natural product dimers. The dimerisation pathways discussed encompass the most prevalent strategies, including: Diels-Alder, Aldol, Mannich, conjugate addition, oxidative, radical and photochemical approaches; each underpinned through rational biosynthetic speculation.
Assuntos
Produtos Biológicos/síntese química , Biomimética/métodos , Técnicas de Química Sintética/métodos , Produtos Biológicos/química , Dimerização , Humanos , Estrutura MolecularRESUMO
A silver-mediated one-step procedure to 2,4-disubstituted and 2,4,5-trisubstituted oxazoles has been developed. The method is complementary to existing technologies, yet provides advantages with regard to simplicity, efficiency, and performance. The silver product can be readily recycled, thus minimizing waste.
Assuntos
Oxazóis/síntese química , Prata/química , Catálise , Química Verde , Oxazóis/químicaRESUMO
hLDH-5 has emerged as a promising target for anti-glycolytic cancer chemotherapy. Here we report a first generation of bifunctional inhibitors, which show promising activity against hLDH-5.
Assuntos
Alcinos/farmacologia , L-Lactato Desidrogenase/antagonistas & inibidores , NAD/farmacologia , Ácido Oxâmico/farmacologia , Triazóis/farmacologia , Alcinos/síntese química , Alcinos/química , Domínio Catalítico/efeitos dos fármacos , Química Click , Cristalografia por Raios X , Glicólise , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5 , Ligantes , Modelos Moleculares , Estrutura Molecular , NAD/síntese química , NAD/química , Ácido Oxâmico/síntese química , Ácido Oxâmico/química , Estereoisomerismo , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/químicaRESUMO
A new synthesis of 1-substituted-1H-indazoles via 1,3-dipolar cycloaddition of nitrile imines to benzyne is described. The reaction is completed within 5 min, affording the corresponding N(1)-C(3) disubstituted indazoles in moderate to excellent yields.
Assuntos
Derivados de Benzeno/química , Iminas/química , Indazóis/síntese química , Nitrilas/química , Técnicas de Química Combinatória , Ciclização , Indazóis/química , Estrutura MolecularRESUMO
An efficient synthesis of a range of 1,2-benzisoxazoles using an improved 1,3-dipolar cycloaddition of nitrile oxides and benzyne is described. Key to the procedure is the in situ generation of the reactive nitrile oxide and benzyne reaction partners mediated by TBAF. Reactions are complete within 30 s, giving the target products in good to excellent yield.
Assuntos
Derivados de Benzeno/química , Isoxazóis/síntese química , Nitrilas/química , Derivados de Benzeno/síntese química , Catálise , Ciclização , Isoxazóis/química , Nitrilas/síntese química , Óxidos/síntese química , Óxidos/químicaRESUMO
An efficient protocol for the synthesis of a range of 1,2-benzisoxazoles using an improved 1,3-dipolar cycloaddition of nitrile oxides and benzyne is described. Key to the procedure is the in situ generation of the reactive nitrile oxide and benzyne reactants simultaneously.