Total synthesis and bioactivities of two proposed structures of maresin.
Maresin is a potent anti-inflammatory lipid mediator derived from docosahexaenoic acid (DHA). A highly convergent total synthesis of two proposed structures of C7-epimeric maresins from the four known fragments was achieved in 17 steps. The three key coupling reactions were the BF(3)-mediated alkyne attack on the epoxide, chiral titanium complex-promoted enantioselective alkyne addition to the aldehyde, and a Julia-Kocienski olefination. The two synthesized diastereomers were found to be comparably active in blocking neutrophil infiltration in the acute peritonitis model.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kenji
K
Sasaki
Daisuke
D
Urabe
Hiroyuki
H
Arai
Makoto
M
Arita
Masayuki
M
Inoue
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D004281:Docosahexaenoic Acids / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010538:Peritonitis / Q000188:drug therapy*; D013237:Stereoisomerism
D000893:Anti-Inflammatory Agents; D004281:Docosahexaenoic Acids