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Synthesis 2009(5): 759-766  
DOI: 10.1055/s-0028-1083373
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Practical Syntheses of Sphingosine-1-Phosphate and Analogues

Virginie Blota, Ulrich Jacquemarda, Hans-Ulrich Reissig*a, Burkhard Kleuserb
a Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Fax: +49(30)83855367; e-Mail: hans.reissig@chemie.fu-berlin.de ;
b Institut für Pharmazie, Freie Universität Berlin, Königin-Luise Str. 2-4, 14195 Berlin, Germany
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Publication History

Received 18 July 2008
Publication Date:
11 February 2009 (online)

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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.