Pseudosugars, 34. Synthesis of 5a‐carba‐β‐D‐glycosylceramide analogs linked by imino, ether and sulfide bridges

Abstract

AbstractCarbocyclic analogs of glycoceramides, (2S,3R,4E)‐1‐(5a‐carba‐β‐D‐glycopyranosyl)‐2‐(hexadecanoylamino)‐4‐octa‐decen‐3‐ols E‐3‐E‐6, linked by imino, ether and sulfide bridges, were synthesized by coupling of aziridines, as the sphingosine precursors, with protected 1‐amino, 1‐hydroxy and 1‐mercapto derivatives of 5a‐carba sugars and subsequent deprotection and N‐acylation. Biological assay of 5a‐carbaglycosylceramides showed that both imino‐linked E‐3 and E‐4 having gluco and galacto configurations are mild immunomodulators and possess a mild inhibitory activity against gluco‐ and galactocerebrosidases. These findings prompted us to prepare the corresponding Z‐isomers Z‐3 and Z‐4, which interestingly show a similar enzyme‐inhibitory activity.