Synthesis of phytosphingosine and phytoceramide probes to study the sphingolipid metabolism in non-alcoholic fatty liver disease

Abstract

Evidence demonstrates that downregulation of DES1 activity, altering dihydroceramides ratio, is involved in the primordial causes of non-alcoholic fatty liver disease (NAFLD). Although DES2 and regulation of phytoceramides are also considered to be involved in the development of this disease, not enough studies exist to prove it. This work has essentially developed and evaluated a synthetic procedure capable of providing both non-natural C17 phytosphingosine and phytoceramide probes with D-ribo-stereochemistry to be used in the study of the stated problem through its administration in mice for HRMS-HPLC monitorization. Some of the probes are commercially available but economically inaccessible for the amounts needed to perform animal assays. Target compounds were characterized by stereochemical control of the dihydroxylation intermediates from their specific optical rotation, NMR analysis and MS. Additionally, the natural C18 phytoceramide was prepared as a reference standard from a commercially available phytosphingosine