Improved, gram scale synthesis of N,O,O-triacetyl-erythro- and threo-C18-sphingosines from serine

Abstract

A formal total synthesis of all four (E)-C₁₈-sphingosine stereoisomers from serine has been carried out. This involves the thiazole-based homologation of the amino acid into a chiral 3-amino-2,4-dihydroxybutanal 1 and the Wittig olefination of 1 with the ylide from the C₁₄ alkyl phosphonium salt 2. The photoisomerization of the resulting mixture of Z- and E-alkenes affords the target sphingosine. Thus, N,O,O-triacetyl-D-erythro C₁₈-sphingosine 5 and the L-threo isomer 10 were prepared in 43–44% overall yield from the aldehyde (S,S)-1a and (2R,3S)-1b, respectively. The corresponding antipodal L-erythro and D-threo isomers can be prepared in the same way starting from aldehydes ent-1a and ent-1b, respectively. Conversion of the above acetyl sphingosines into the free sphingoid bases has been reported in the literature.