RESUMEN
The bengazoles are a family of marine natural products that display potent antifungal activity and a unique structure, containing two oxazole rings flanking a single carbon atom. Total syntheses of bengazole A and B are described, which contain a sensitive stereogenic centre at this position between the two oxazoles. Additionally, the synthesis of 10-epi-bengazole A is reported. Two parallel synthetic routes were investigated, relying on construction of the 2,4-disubstituted oxazole under mild conditions and a diastereoselective 1,3-dipolar cycloaddition. Our successful route is high yielding, provides rapid access to single stereoisomers of the complex natural products and allows the synthesis of analogues for biological evaluation.
Asunto(s)
Antifúngicos/síntesis química , Oxazoles/síntesis química , Antifúngicos/química , Procesamiento Automatizado de Datos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Oxazoles/química , Espectroscopía Infrarroja por Transformada de Fourier , EstereoisomerismoAsunto(s)
Antifúngicos/farmacología , Miconazol/síntesis química , Antifúngicos/síntesis química , Antifúngicos/química , Candida albicans/efectos de los fármacos , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Biología Marina , Miconazol/química , Miconazol/farmacología , Oxazoles/química , EstereoisomerismoRESUMEN
[reaction: see text] gamma,delta-Unsaturated alpha-hydroxy diesters with quaternary centers have been obtained with up to 99% ee in high yields using catalysts prepared from copper(II) triflate and C(1)-symmetric aminosulfoximines.
RESUMEN
The development of C1-symmetric aminosulfoximines, their highly modular synthesis, and their application in enantioselective copper-catalyzed Mukaiyama-type aldol reactions between pyruvates and enolsilanes is described. In this context, the influence of the ligand architecture as well as the optimization of the reaction conditions are discussed. In detail, the dependence of the catalyst efficiency on the solvent, the metal source and the temperature are reported, and an interesting additive effect is highlighted. Furthermore, the substrate scope will be presented. With the optimized catalyst system, a number of aldol products with quaternary stereogenic centers have been obtained in high yields and with enantiomeric excesses up to 99 %.