Total syntheses of symbioramide derivatives from L-serine and their antileukemic activities

Naturally occurring symbioramide, (2S,3R,2'R,3'E)-N-(2'-hydroxy-3'-octadecenoyl)-dihydrosphingosine la, was synthesized from D-erythro-dihydrosphingosine (amino part, 2) and (2R,3E)-2-hydroxy-3-octadecenoic acid (acid part, 3a), both of which were prepared from L-serine. Its diastereomer, (2S,3R,2'S,3'E)-1b, having an enantiomer of the unnatural-type acid part that was prepared from D-mannitol, and its corresponding (Z)-isomers, (2S,3R,2R,3'Z)-1c and (2S,3R,2'S,3'Z)-1d, were also prepared. The antileukemic activities of 1a-d against HL-60 and L-1210 cells were appreciated by a MTT assay. None of the four symbioramide derivatives showed antileukemic activities in HL-60 cells. In L-1210 cells, all the symbioramide derivatives showed moderate antileukemic activities. Compound 1d had the most effective activity against L-1210 cells among the four derivatives. The data suggest that unnatural types of (2'S)-isomers of acid parts are more active than those of (2R)-isomers.