Sphingosine and Phytosphingosine from D-Threose Synthesis of a 4-Keto-Ceramide

Article abstract of DOI:10.1016/S0957-4166(00)86295-3

Reaction of 2,4-O-benzylidene-D-threose 3 with tetradecyl magnesium bromide furnished D-arabino- and L-xylo-octadecane-1,2,3,4-tetrols 5a,x.Regioselective oxidation of the 4-OH group gave 4-keto-D-erythro-derivative 6 which can be reduced with acetaldehyde in a SmI2-catalyzed Tishtshenko reaction to afford exclusively 5a.Regioselective 2-O-mesylation of 5a ( -> 7a) and then acid catalyzed debenzylation afforded exclusively 2-O-mesyl-tetrol 9a.Reaction with NaN3 and ensuing azide reduction furnished D-ribo-C18-phytosphingosine (2) in high overall yield.Treatment of 2-O-mesyl derivatives 7a,x with NaN3 and then with 4-nitrobenzenesulfonyl chloride in pyridine afforded 11r,l.Elimination with DBU or, alternatively, by treatment with phenylselenide and then with H2O2, gave known 1,3-O-benzylidene protected azidosphingosine 14, which can be readily converted into sphingosine (1).Transformation of 2 into ceramide 15, selective 1,3-O-silyl protection, oxidation of the 4-OH group ( -> 17) and then desilylation afforded the 4-keto ceramide 18 found in a marine sponge.Reduction of 17 offers a convenient possibility for radioactive labelling of ceramides with tritium.