RESUMO
The C-arylglycosides are available in enantiomerically pure form via the Dötz benzannulation reaction between Fischer alkenyl chromium carbene complexes and alkynes; it also could be converted to a precursor of medermycin by O-carbamate directed ipso bromination and nitrile substitution in good overall yields.
Assuntos
Estrutura Molecular , Naftoquinonas/síntese química , Naftoquinonas/química , EstereoisomerismoRESUMO
4-aminoquinolines, classically prepared via SNAr chemistry from an amine and 4-haloquinoline, are important scaffolds in medicinal chemistry. Interest in these compounds prompted us to explore palladium catalysis as an alternative to the existing methods for their preparation. Initial results followed by an iterative screening paradigm confirmed Pd(OAc)2/DPEphos/K3PO4 as a mild and convenient alternative for the formation of the C-N bond in 4-aminoquinolines. A description of the screen and the scope of this methodology are discussed herein.
Assuntos
Aminoquinolinas/síntese química , Aminas/química , Catálise , Métodos , Paládio/química , Quinolinas/químicaRESUMO
A series of non-covalent inhibitors of the serine protease dipeptidyl peptidase IV (DPP-IV) were found to adopt a U-shaped binding conformation in X-ray co-crystallization studies. Remarkably, Tyr547 undergoes a 70 degrees side-chain rotation to accommodate the inhibitor and allows access to a previously unexposed area of the protein backbone for hydrogen bonding.
Assuntos
Inibidores da Dipeptidil Peptidase IV , Inibidores de Proteases/síntese química , Inibidores de Proteases/farmacologia , Animais , Sítios de Ligação , Simulação por Computador , Cristalografia por Raios X , Dipeptidil Peptidase 4/sangue , Avaliação Pré-Clínica de Medicamentos , Ligação de Hidrogênio , Masculino , Modelos Moleculares , Conformação Molecular , Inibidores de Proteases/química , Ratos , Ratos Wistar , Espectrometria de FluorescênciaRESUMO
[reaction: see text] A synthesis of (S,S)-isodityrosine 1, a naturally occurring, key structural subunit of numerous biologically active macromolecules, is described. A formal [3 + 2 + 1] cycloaddition (Dötz benzannulation) approach was utilized to simultaneously construct an aromatic ring and the diaryl ether linkage in one step. This key step was extended to the synthesis of (S,S)-isodityrosine in two separate convergent synthetic routes. This method demonstrates a novel and mild method for the synthesis of diaryl ethers.