RESUMO
Promising synthetic derivatives of macrolactone natural product (-)-A26771B have been designed and synthesized both from semisynthesis and total synthesis. Further optimization led to the first synthesis of macrolactam analogs of (-)-A26771B with improved antibacterial activity and metabolic stability.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Fatores Biológicos/farmacologia , Antibacterianos/síntese química , Antibacterianos/metabolismo , Fatores Biológicos/síntese química , Fatores Biológicos/metabolismo , Relação Dose-Resposta a Droga , Desenho de Fármacos , Lactonas/síntese química , Lactonas/metabolismo , Lactonas/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A conformational study of branimycin was performed using single-crystal X-ray crystallography to characterize the solid-state form, while a combination of NMR spectroscopy and molecular modeling was employed to gain information about the solution structure. Comparison of the crystal structure with its solution counterpart showed no significant differences in conformation, confirming the relative rigidity of the tricyclic system. However, these experiments revealed that the formerly proposed stereochemistry of branimycin at 17-C should be revised.
Assuntos
Macrolídeos/química , Cristalografia por Raios X , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , EstereoisomerismoRESUMO
[reaction: see text] A concise and efficient total synthesis of biphenomycin B has been accomplished featuring a key microwave-assisted intramolecular Suzuki-Miyaura reaction for formation of the 15-membered meta,meta-cyclophane 20.