Fluorinated triazole-containing sphingosine analogues

Syntheses and in vitro evaluation as SPHK inhibitors

M. Escudero-Casao, A. Cardona, R. Beltrán-Debón, Y. Díaz, M. Isabel Matheu, S. Castillón
Org. Biomol. Chem. 2018, 16, 7230-7235.

Sphingosine analogues with a rigid triazole moiety in the aliphatic chain and systematic modifications in the polar head and different degrees of fluorination at the terminus of the alkylic chain were synthesized from a common alkynyl aziridine key synthon. This key synthon was obtained by enantioselective organocatalyzed aziridination and it was subsequently ring opened in a regioselective manner in acidic medium. Up to 16 sphingosine analogues were prepared in a straightforward manner. The in vitro activity of the obtained products as SPHK1 and SPHK2 inhibitors was evaluated, displaying comparable activity to that of DMS.

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