Sphingosine, acetylation synthesis

The aziridine-2-carboxaldehyde 56 can also serve as synthon for the synthesis of sphingosines, which are important biomembrane constituents [64]. One possible route involves the addition of an alanate to the aldehyde. In a later stage of this synthetic plan the aziridine can be opened, either via the intermediacy of an oxazoline or directly with dilute acid. Unfortunately, the reaction of aldehyde 56 with a vinylalanate has a poor diastereoselectivity of 3 2. Therefore, an alternative approach was considered, namely one involving the addition of a vinylzinc reagent to the aldehyde thereby employing our N-tritylaziridinediphenyl-methanol 51 as the chiral catalyst. Gratifyingly, only one diastereomer was obtained. Reductive removal of the trityl function, acetylation of the hydroxy... 

Reaction 18 was shown to occur in the presence of guinea-pig or rat-brain microsomes. Ceramides were stated to be inactive as the acceptor of D-galactose residues, but it appears that only N-acetyl-sphingosine was used. Also, inactivity of any of the substrates in these reactions could be due to the lack of proper emulsification. Reaction 19 was postulated by R. O. Brady, when he reported on the first enzymic synthesis of cerehrosides with rat-hrain microsomes and stearoyl- C-CoA. In a reaction mixture containing psychosine as an acceptor, twice as much stearic acid- C was incorporated as in the mixture containing a combination of sphingosine and UDP-D-glucose instead of psychosine. ... 

An acylase converts sphingosine to the ceramide by condensing a long-chain fatty acid molecule with the base. A fatty acyl-CoA acid acts as donor. Both palmitic and stearic acetyl-CoA [110] may be used for the synthesis of ceramides (see Figs. 3-30 and 3-31). Stearic acid is the predominant fatty acid in brain gangliosides. It forms 72% of the fatty add of shark... 

During the synthesis of sphingosine-1-phosphate lyase (SIPL) inhibitor for the treatment of autoimmune disorders, Bagdanoff and co-workers prepared the a,a-difluoro analog of 2-acetyl-4(5)-[l(f ),2(5),3(f ),4-tetrahydroxybutyl]imidazole (Scheme 20) [30], Ketalization of the diol using 2,2-dimethoxypropane followed by the treatment of bisketal with DAST and subsequent deprotection afforded the targeted 2-(l,l-difluoroethyl)imidazole derivative. 

This enzyme, which has been purified some 200-fold, also catalyzes the synthesis of ceramide from sphingosine and free fatty acid. Acyl CoA derivatives are active only after hydrolysis by thiolase to release free fatty acid which is then available to condense with sphingosine. Attempts to dissociate these enzymic processes from one another have been unsuccessful. The preparation showed hydrolytic activity (ceramidase) toward A-palmitoyl, oleoyl, and stearoyl sphingosine, as well as with. V-palmitoyl dihydrosphingosine. Cerefarosides, sphingomyelin, and iV-acetyl sphingosine were not cleaved. 

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