Facile synthesis of the CERT inhibitor HPA-12 and some novel derivatives
Essa M Saied1, Stephanie Diederich, Christoph Arenz
1Institute for Chemistry, Humboldt Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin (Germany), Fax: (+49) 30-2093 6947; Chemistry Department, Faculty of Science, Suez Canal University, Ismailia (Egypt).
Abstract:
HPA-12 is an inhibitor of CERT-mediated non-vesicular transport of ceramide from the ER membranes to the Golgi apparatus. The inhibitor effectively blocks the synthesis of the membrane lipid sphingomyelin and may represent a novel drug prototype. Previous syntheses relied on non-commercial catalysts or specialized chemistries. Here we present a straightforward and effective method to synthesize HPA-12 from commercially available protected L-serinol in four steps. Some new analogues were synthesized and evaluated for their CERT-binding activity.
