Practical Syntheses of Sphingosine-1-Phosphate and Analogues

Abstract

Sphingosine-1-phosphate (S1P, 1) is a bioactive sphingolipid metabolite involved in a variety of critical cellular processes including proliferation, survival, and migration. For this reason the stereoselective syntheses of S1P and analogues are of great interest. Based on l-serine as source of chirality we achieved practical routes to prepare S1P (1) and the aryl group containing analogues 3 and 4 in fair amounts. The crucial stages of the syntheses are: introduction of the required side chain by addition of appropriate organometallics to Garner’s aldehyde and conversion of the primary alcohols into the corresponding phosphates.

Key words

phosphates - amino alcohols - lipids - organometallic reagents - sphingosine derivatives

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17

The scaling-up, essentially following our protocol, provided S1P 1 in quantities of more than 100 g.