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 1a, 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,2'R,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 (2'R)-isomers.
Azuma
Hideki
H
Department of Applied & Bioapplied Chemistry, Graduate School of Engineering, Osaka City University, Sugimoto 3-3-138, Sumiyoshi-ku, Osaka 558-8585, Japan. ogino@bioa.eng.osaka-cu.ac.jp
Takao
Ryoko
R
Niiro
Hayato
H
Shikata
Keiji
K
Tamagaki
Seizo
S
Tachibana
Taro
T
Ogino
Kenji
K
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D007938:Leukemia / Q000209:etiology; D051379:Mice; D015394:Molecular Structure; D012694:Serine; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; C057218:symbioramide; D012694:Serine; D013110:Sphingosine