RESUMEN
The synthesis of 7-oxasphingosine (3) and 7-oxaceramide (4) was improved by starting from the 4-methoxybenzyl-protected d-galactal 9. The sphingosine analogues 5-7 and 24 were synthesized via the azido alcohol 13. The 7-thiasphingosine 5 is a poorer substrate for both isoforms of sphingosine kinase (SPHK) than sphingosine, but showed a slight preference for SPHK2. The sulfone 6 and the 7-aza compounds 7 and 24 were not phosphorylated by either SPHK1 or SPHK2, and none of 5-7 and 24 activated invariant natural killer T (iNKT) cell clones when presented by human CD1d-transfected antigen-presenting cells (APC) or by plate-bound human CD1d. Only 7 and 24 associated with plate-bound recombinant CD1d prevented stimulation of iNKT cells by alpha-galactosylceramide (alpha-GalCer).
Asunto(s)
Ceramidas/química , Células T Asesinas Naturales/inmunología , Fosfotransferasas (Aceptor de Grupo Alcohol)/química , Esfingosina/química , Células Presentadoras de Antígenos/inmunología , Antígenos CD1d/genética , Antígenos CD1d/inmunología , Ceramidas/síntesis química , Ceramidas/farmacología , Humanos , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Esfingosina/síntesis química , Esfingosina/farmacologíaRESUMEN
A short, convergent synthesis of the mushroom pigment norbadione A is described. The construction of an appropriately substituted naphtholactone intermediate involved a regioselective Diels-Alder reaction between a bis(triisopropylsilyloxy)diene and 2,6-dichlorobenzo-1,4-quinone. A double Suzuki-Miyaura cross-coupling between a diboronate and two identical enol triflates was another key feature of the synthesis.
