Synthesis of new trans double-bond sphingolipid analogues: Delta(4,6) and Delta(6) ceramides

J Org Chem. 2002 Apr 19;67(8):2600-5. doi: 10.1021/jo0162639.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Catalysis
  • Ceramides / chemical synthesis*
  • Chemistry, Organic / methods
  • Chromatography, Thin Layer
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Spectrophotometry, Infrared
  • Spectroscopy, Fourier Transform Infrared
  • Stereoisomerism

Substances

  • Ceramides