RESUMO
The dicyclohexylborane-mediated addition of allene 1 to (E)-2-tridecenal affords a quaternary protected 2-amino-2-vinyl-1,3-diol in good yield as a single diastereomer. This compound is readily transformed into the four stereoisomers of the quaternary (E)-2-vinyl analogs of sphingosine. The metabolic fate and the effect of these compounds on the basal sphingolipid metabolism in human A549 lung adenocarcinoma cells has been studied, together with the ceramide analog of the most relevant vinylsphingosine derivative.
Assuntos
Ceramidas/síntese química , Ceramidas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Esfingolipídeos/metabolismo , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Células A549 , Sobrevivência Celular , Humanos , Serina C-Palmitoiltransferase/antagonistas & inibidores , Esfingolipídeos/química , Esfingosina/síntese química , EstereoisomerismoRESUMO
Treatment of readily available allene 1 with Cy2BH followed by addition of an aldehyde led to quaternary protected 2-amino-2-vinyl-1,3-diols in high yield and excellent stereochemical purity. The choice of benzoyl as N-protecting group is critical since the observed N- to O-Bz transfer during the process prevents later undesired isomerizations in the adducts and keeps all heteroatoms protected.
