45] Practical synthesis of N-palmitoylsphingomyelin and N-palmitoyldihydrosphingomyelin

Abstract

Sphingolipids play a significant role in the structural organization of biological membranes, and numerous intra- and intercellular processes are dependent on their metabolism and catabolism. Over the past decade, sphingolipids and their metabolites have generated a great deal of interest due to the discovery of the sphingomyelin cycle in which ceramide plays an important role in the regulation of cell growth, differentiation, and cell death. Sphingolipids have also been implicated in the development of general types of tumors, and there are several reports that the dietary sphingolipids can affect and even reverse the development of carcinogenesis. The success of these and many other investigations depends on the accessibility of sphingolipids, which are used as substrates. Many kinds of sphingolipids can be isolated easily from natural sources; however, these compounds are not chemically homogeneous with respect to sphingosine bases or fatty acids. It is clear that the heterogeneity of these moieties affects both physicochemical characteristics and biological functions of the sphingolipids. The semisynthetic preparation of sphingomyelins and other sphingolipids through their lyso derivatives provides a way to obtain compounds in which the fatty acid is homogeneous, while the sphingosine base composition remains nonhomogeneous. Prepared by this method, substrates may be contaminated with the threo isomers because of epimerization at the C-3-atom, which occurs in the process of acidic deacylation of the natural materials. Commercial sphingolipids can be contaminated with other biologically active compounds, which can exhibit the same or different activity. Total chemical synthesis allows the preparation of individual homogeneous natural compounds with a completely defined structure in any desirable quantities for biophysical and biochemical studies. Chemically prepared substrates with variations in a core structure may be used for elucidating variations in the structure-dependent biochemical and biophysical properties.