RESUMEN
Microbial hydroxylation of o-bromophenylacetic acid provided 2-bromo-5-hydroxyphenylacetic acid. This enabled a route to the key intermediate 4-bromo-2,3-dihydrobenzofuran for synthesizing a melatonin receptor agonist and sodium hydrogen exchange compounds. Pd-mediated coupling reactions of 4-bromo-2,3-dihydrobenzofuran provided easy access to the 4-substituted-2,3-dihydrobenzofurans.
Asunto(s)
Aspergillus/metabolismo , Benzofuranos/metabolismo , Fenilacetatos/metabolismo , Biotransformación , Hidroxilación , Estructura MolecularRESUMEN
The C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in a dose-dependent manner by as much as 55% in hyperglycemic streptozotocin (STZ) rats. These findings, combined with a favorable ADME profile, have prompted clinical evaluation of dapagliflozin for the treatment of type 2 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/síntesis química , Hipoglucemiantes/síntesis química , Riñón/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Administración Oral , Animales , Compuestos de Bencidrilo , Glucemia/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucósidos/química , Glucósidos/farmacología , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Ratas , Transportador 2 de Sodio-Glucosa , EstereoisomerismoRESUMEN
An efficient and practical process to generate beta-C-arylglucoside derivatives was achieved. The process described involves Lewis acid mediated ionic reduction of a peracetylated 1-C-aryl methyl glucoside derived from the addition of an aryl-Li to selectively protected delta-D-gluconolactone. The reduction of the 2-acetoxy-1-C-oxacarbenium ion intermediates proceeds with a high degree of selectivity to give beta-C-arylglucosides without 2-acetoxy group participation. Furthermore, during the reduction process we also identified an unprecedented critical role of water. By changing from the usual benzyl ether protecting groups because of cost and chemical compatibility concerns, the new process is made additionally efficient and highly selective.