Total synthesis of four stereoisomers of (5Z,8Z,10E,14Z)-12-hydroxy-17,18-epoxy-5,8,10,14-eicosatetraenoic acid and their anti-inflammatory activities

Tomomi Goto, Daisuke Urabe, Yosuke Isobe, Makoto Arita, Masayuki Inoue

研究成果: Article査読

2 被引用数 (Scopus)

抄録

The four stereoisomers of novel lipid mediator 1, (5Z,8Z,10E,14Z)-12-hydroxy-17,18-epoxy-5,8,10,14-eicosatetraenoic acid, were synthesized from six simple fragments. Triyne 2 was convergently assembled through three SN2 alkynylation reactions and one Sonogashira coupling reaction. Two of the three alkynes of 2 were hydrogenated using Lindlar catalyst, while the third alkyne was reduced through formation of the alkyne-dicobalt hexacarbonyl complex and subsequent reductive decomplexation, producing the requisite tetraene structure in a stereoselective manner. Next, a two-step functional group manipulation at C1, followed by simultaneous deprotection and epoxide formation, gave rise to the four isomers, (12S,17R,18S)-1aa, (12S,17S,18R)-1ab, (12R,17R,18S)-1ba and (12R,17S,18R)-1bb. The present work allowed determination of the absolute structure of naturally occurring 1 to be 1aa and 1ab, as well as biological evaluation of the two natural (1aa, 1ab) and two unnatural (1ba, 1bb) isomers. Intriguingly, natural 1aa and unnatural 1ba were found to exhibit more potent anti-inflammatory activities than 1ab and 1bb, indicating the greater importance of the stereochemistry of the C17,18-epoxide compared to that of the C12-hydroxy group.

本文言語English
ページ(範囲)8320-8332
ページ数13
ジャーナルTetrahedron
71
43
DOI
出版ステータスPublished - 2015 10月 28
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 創薬
  • 有機化学

フィンガープリント

「Total synthesis of four stereoisomers of (5Z,8Z,10E,14Z)-12-hydroxy-17,18-epoxy-5,8,10,14-eicosatetraenoic acid and their anti-inflammatory activities」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル