RESUMO
We have developed a versatile synthetic strategy for the synthesis of the natural product diptoindonesin G and its analogues as selective modulators of estrogen receptors. The strategy involves a regioselective dehydrative cyclization of arylacetals, a regioselective bromination of benzofurans, a sequential cross-coupling of bromo-benzofurans with aryl boronic acids, and a BBr3-mediated tandem cyclization and demethylation. Preliminary biological studies uncovered the critical and dispensable phenolic hydroxyl groups in the natural product and also revealed unexpected selectivity for isoforms of estrogen receptor.
Assuntos
Benzofuranos/síntese química , Benzofuranos/farmacologia , Receptores de Estrogênio/metabolismo , Acetais/síntese química , Acetais/química , Acetais/farmacologia , Benzofuranos/química , Ácidos Borônicos/síntese química , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Ciclização , Halogenação , Humanos , Células MCF-7 , Estabilidade Proteica/efeitos dos fármacos , EstereoisomerismoRESUMO
All eight possible stereoisomers of 2,3,6-trideoxyhexopyranosides are prepared systematically from furan derivatives by a sequence of Achmatowicz rearrangement, Pd-catalysed glycosidation, and chiral catalyst-controlled tandem reductions. This sequence provides access to all possible stereoisomers of naturally occurring rhodinopyranosides, amicetopyranosides, disaccharide narbosine B, and other unnatural oligomeric 2,3,6-trideoxyhexopyranosides. It comprises a unique and systematic strategy for the de novo synthesis of deoxysugars.
