Total synthesis of an immunosuppressive glycolipid, (2S,3S,4R)-1-O- (alpha-d-galactosyl)-2- tetracosanoylamino-1,3,4-nonanetriol.
[reaction: see text] A practical and efficient total synthesis of (2S,3S,4R)-1-O-(alpha-d-galactosyl)-2-tetracosanoylamino-1,3,4-nonanetriol, OCH 1b, a potential therapeutic candidate for Th1-mediated autoimmune diseases, is described. The synthesis incorporates direct alkylation onto epoxide 5 and stereospecific halide ion catalyzed alpha-glycosidation reaction. A key intermediate 10 was obtained in only eight steps and 37% overall yield from commercially available d-arabitol 2, and the total synthesis of 1b was accomplished in 12 steps and 19% overall yield. This method will enable the synthesis of a variety of phytosphingolipids, especially that with the shorter sphingosine side chain than 1a, in a highly stereoselective manner.
Murata
Kenji
K
Daiichi Suntory Biomedical Research Co., Ltd., 1-1-1, Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8513, Japan.
Toba
Tetsuya
T
Nakanishi
Kyoko
K
Takahashi
Bitoku
B
Yamamura
Takashi
T
Miyake
Sachiko
S
Annoura
Hirokazu
H
D006028:Glycosphingolipids / Q000138:chemical synthesis*; D007166:Immunosuppressive Agents / Q000138:chemical synthesis*; D008968:Molecular Conformation
D006028:Glycosphingolipids; D007166:Immunosuppressive Agents