Synthesis and characterization of some atypical sphingoid bases

Sphingolipids are ubiquitous and abundant components of all eukaryotic and some prokaryotic organisms. Sphingolipids show a large structural variety not only between the different species, but also within an individual cell. This variety is not limited to alterations in the polar headgroups of e.g. glycosphingolipids, but also affects the lipophilic anchors comprised of different fatty acids on the one hand and different sphingoid bases on the other hand. The structural variations within different sphingoid bases e.g. in pathogens can be used to identify novel biomarkers and drug targets and the specific change in the profile of common and uncommon sphingolipids are associated with pathological conditions like diabetes or cancer. Therefore, the emerging field of sphingolipidomics is dedicated to collect data on the sphingolipidome of a cell and hence to assign changes therein to certain states of a cell or to pathological conditions. This powerful tool however is still limited by the availability of structural information about the individual lipid species as well as by the availability of appropriate internal standards for quantification. Herein we describe the synthesis of a variety of 1-deoxy-sphingoid bases. 1-DeoxySphingolipids have recently acquired significant attention due to its pathological role in the rare inherited neuropathy, HSAN1 but also as predictive biomarkers in diabetes type II. Some of the compounds synthesized and characterized herein, have been used and will be used to elucidate the correct structure of these disease-related lipids and their metabolites.