Alessondro Dondoni, Daniela Perrone and Elisa Turturici
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.