[391 Synthesis of Sphingosine and Sphingoid Bases

Sphingosines are a related class of long chain aliphatic compounds possessing a 2-amino-l,3-diol moiety. The most common member of this group found in nature is ( 2 S , 3 R ) D e r y t h r o 2 a m i n o l , 3 o c t a d e c 4 E e n e diol l a and is frequently referred to as sphingosine. These molecules are the backbone of more complex sphingolipids, including ceramide, sphingomyelin, cerebrosides, and glycosphingolipids. Ubiquitous to all living organisms, sphingolipids play many biologically important roles. As major constituents of membranes, they contribute to the structural integrity of a cell. Furthermore, sphingolipids facilitate cell-cell signaling, cell recognition, and adhesion. 1'1~' Given the obvious significance of sphingolipids, efforts for the synthetic preparation of sphingosine and related analogs have generated much interest. There have been many published syntheses of sphingosine and its derivatives in the literature since the first reported sphingosine synthesis by Shapiro, 2'2a with each synthesis offering something unique. Some syntheses utilize inexpensive starting materials from the chiral pool, whereas others control stereochemistry through asymmetric induction. High yield and few steps may be the hallmark of some preparations, whereas synthetic elegance, stereoselectivity, or the ability to convert to other sphingolipids or natural products may be the attributes of others. Because of this wealth of approaches chemists have a variety of choices for the preparation of synthetic sphingoid bases, but determining which procedure to use depends on the researcher's specific needs. The aim of this article is to illustrate and summarize many protocols, provide insights about each preparation and, in this way, facilitate the selection of sphingolipid synthetic preparations. Sphingosine syntheses can be divided into several categories. Syntheses that start from chiral precursors are divided into those that begin with serine derivatives and those that begin with sugar derivatives. Syntheses that