RESUMO
Two complementary methods for the synthesis of fluorinated exo-glycals have been developed, for which previously no general reaction had been available. First, a Selectfluor-mediated fluorination was optimized after detailed analysis of all the reaction parameters. A dramatic effect of molecular sieves on the course of the reaction was observed. The reaction was generalized with a set of biologically relevant furanosides and pyranosides. A second direct approach involving carbanionic chemistry and the use of N-fluorobenzenesulfonimide (NFSI) was performed and this method gave better diastereoselectivities. Assignment of the Z/E configuration of all the fluorinated exo-glycals was achieved based on the results of HOESY experiments. Furthermore, fluorinated exo-glycal analogues of UDP-galactofuranose were prepared and assayed against GlfT2, which is a key enzyme involved in the cell-wall biosynthesis of major pathogens. The fluorinated exo-glycals proved to be potent inhibitors as compared with a series of C-glycosidic analogues of UDP-Galf, thus demonstrating the double beneficial effect of the exocyclic enol ether functionality and the fluorine atom.
Assuntos
Compostos de Diazônio/química , Inibidores Enzimáticos/química , Galactose/análogos & derivados , Galactosiltransferases/antagonistas & inibidores , Sulfonamidas/química , Difosfato de Uridina/análogos & derivados , Antituberculosos/síntese química , Antituberculosos/química , Antituberculosos/farmacologia , Compostos de Diazônio/síntese química , Compostos de Diazônio/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Galactose/síntese química , Galactose/química , Galactose/farmacologia , Galactosiltransferases/metabolismo , Halogenação , Humanos , Modelos Moleculares , Mycobacterium tuberculosis/enzimologia , Sulfonamidas/síntese química , Sulfonamidas/farmacologia , Tuberculose/tratamento farmacológico , Difosfato de Uridina/síntese química , Difosfato de Uridina/química , Difosfato de Uridina/farmacologiaRESUMO
Bump the base: This study reports the discovery of the base-induced Z-to-E isomerization of exo-glycals bearing an electron-withdrawing group (EWG). The scope of this novel transformation regarding the carbohydrate unit is also discussed. After elucidating the mechanism, preparation of novel (E)-exo- glycals was performed (TBS = tert-butyldimethylsilyl).
Assuntos
Álcalis/química , Carboidratos/química , Éteres/química , Organofosfonatos/química , EstereoisomerismoRESUMO
Highly ( Z)-diastereoselective approaches for the synthesis of trifluoromethylated exo-glycals by copper and photoredox catalysis are described. These complementary reactions are applicable to a wide range of methylene exo-glycals generated from the corresponding pyranoses and furanoses and give trifluoromethylated compounds under mild conditions in moderate to good yields. DFT calculations have allowed a rationalization of the observed ( Z)-stereoselectivity.
RESUMO
The insertion reaction of diazocarbonyls to acids could be performed smoothly in fluorinated alcohols in the absence of metal catalyst. This new procedure allowed the chemoselective preparation of various functionalized compounds such as acyloxyesters, depsipeptides, and sulfonate, phosphonate, or boronate derivatives.
Assuntos
Álcoois/química , Compostos de Diazônio/química , Cetonas/química , Alcanossulfonatos/síntese química , Alcanossulfonatos/química , Ácidos Borônicos/síntese química , Ácidos Borônicos/química , Catálise , Técnicas de Química Combinatória , Halogenação , Estrutura Molecular , Organofosfatos/síntese química , Organofosfatos/químicaRESUMO
Novel fluorinated analogues of goniothalamin 1 and howiinol A 2 have been prepared from trifluorocrotonate derivatives. Trifluoromethyl goniothalamin (R/S) 4 showed a slightly lower activity than 1, while the trifluoromethyl howiinol A 16 exhibited similar activities on several cell lines in the micromolar range. Unlike (R) goniothalamin and howiinol A, trifluoromethyl parent compounds remained unchanged when submitted to biomimetic oxidative systems.