Sphingosine, alkylated

Constructing a quaternary center by the alkylation of azlactones has led to development of a new strategy for the synthesis of sphingosine analogs. The azlactone derived from alanine was alkylated with a gem-diacetate to give a 10.5 1 mixture of diastereomers both with 89% ee [191 ]. 

In 2006, Rezanka etal44 isolated an antifeedant, syriacin (59), from the freshwater sponge Ephydatia syriaca in the Jordan river. It is an unusual sulfated ceramide glycoside with branched-chain sphingosine and also a branched-chain fatty acid. From the viewpoint of absolute configuration, 59 is very unusual, because it contains both (if)- and (.V)-configured. rcc-butyl terminals in its alkyl chains. It seems to be biosynthesized from precursors with opposite absolute configuration. 

Clemens, J. J., Davis, M. D., Lynch, K. R., Macdonald, T.L. Synthesis of para-alkyl aryl amide analogues of sphingosine-l-phosphate discovery of potent SIP receptor agonists. Bioorg Med Chem Lett 13 (2003) 3401-3404. 

In nature one also finds chiral fatty acid or fatty alcohol derivatives with a hydroxyl or amino substituent at the alkyl chain. Common examples are given in Table 2.2.2 of the fatty acids in cheap commercial castor oil (a fat mixture) consist of ricinoleic acid (12-/ -hydroxy-9-Z-octadecene-carboxylic acid). The hydrogenation product (R)-12-hydroxy-stearic acid is the cheapest chiral fatty acid (about 100/g). Sphingosin (2-S-amino-4-E-octadecene-l,3-R-diol) is a chiral a--arnino-diol, which is found in large amounts in nerve tissue ( 5,000/g). Chirality is expensive, if it is localized within the hydrophobic chain. 

Glycolipids.—2-G-Acyl-l-0-alkyl-3-C>-(j8-D-galactopyranosyl 3-sulphate)-gIycerol has been labelled with [ S]sulphate the labelled glycolipid was used as the substrate in studies of the specificities of human arylsulphatases A and B. Oxidative ozonolysis of the alkenic bond of the sphingosine moiety of either globoside (47) or the methyl ester of haematoside (48) allowed the product to be... 

D-Xylose and D-arabinose have been employed (in a parallel sequence of reactions) for the synthesis of the D- +)-erythro and L- -)-threo sphingosines 185 and 186 respectively. The key step, illustrated in Scheme 40, involved a double elimination (to generate an alkyne) followed by alkylation. 

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