Sphingosine, acetylation

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... 

Precoated silica gel plates (silica gel 60) were purchased from Scientific Products. Bio-Sil A (200 - 400 Mesh) was obtained from Bio-Rad Laboratories. Fatty acid methyl esters, sphingosine and dihydrosphingosine were products of Supelco, Inc. as were 10% DEGS-PS, 3% SP-2340 and 3% OV-17 (all on Supelcoport support). N-acetyl and N-glycolyl neuraminic acid, DEAE-Sephadex A50 and neuraminidase type IX were obtained from Sigma Company. Ganglio-side standards from human brain and neutral glycosphingolipid standards from bovine erythrocytes were prepared in this laboratory. 

The degradation of N-acetyl-di-0-acetyl-CI8-sphingosine (4) with ozone gives13,14 3-amino-2-hydroxybutyrolactone (5) and tetra-decanal (6). 

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. ... 

Figure 12.16 Sphingolipid biosynthesis in Pichia ciferrii. Enzymes are shown as ovals and named according to the corresponding homologues from Saccharomyces cerevisiae. Abbreviations AcTR, acetyl-CoA long-chain base acetyltransferase TAPS, tetraacetyl phytosphingosine TriASa, triacetyl sphinganine TriASo, triacetyl sphingosine IP, inositol phosphoryl. TAPS is by far the most abundant sphingolipid formed in wild-t5 e cells, as reflected by the strength of the arrows.

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