Synthesis of new trans double-bond sphingolipid analogues: Delta(4,6) and Delta(6) ceramides.
Unsaturation was introduced at Delta(4,6) and Delta(6) of the sphingoid chain of naturally occurring ceramide 1 via a beta-keto sulfoxide (12) and sulfone (18) derived from N-Boc-L-serine methyl ester acetonide (9), affording two novel ceramide analogues, (2S,3R)-2-octanoylamidooctadeca-(4E,6E)-diene-1,3-diol (2) and (2S,3R)-2-octanoylamidooctadec-(6E)-ene-1,3-diol (3). After C-alkylation of 12 with (E)-1-bromo-2-tetradecene (8), a trans double bond was installed by elimination of PhS(O)H, providing conjugated dienone oxazolidine 13. Reaction of 18 with 8, followed by desulfonation (Al(Hg)), afforded keto-oxazolidine 20, which bears a (E)-Delta(6) double bond. The syntheses of analogues 2 and 3 from ketones 13 and 20, respectively, were completed by the following sequence of reactions: diastereoselective reduction (NaBH(4)/CeCl(3) or DIBAL-H), hydrolysis of the oxazolidine ring, liberation of the amino group, and installation of the N-amide group.
Chun
Jiong
J
Department of Chemistry and Biochemistry, Queens College of The City University of New York, Flushing, NY 11367-1597, USA.
Li
Guoqing
G
Byun
Hoe-Sup
HS
Bittman
Robert
R
D002384:Catalysis; D002518:Ceramides / Q000138:chemical synthesis*; D002625:Chemistry, Organic / Q000379:methods; D002855:Chromatography, Thin Layer; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
D002518:Ceramides