Novel Approaches towards the LTD4/E4 Antagonist, LY290154

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• 作者：Alain Merschaert ; Pascal Boquel ; Jean-Pierre Van Hoeck ; Hugo Gorissen ; Alfio Borghese ; Benjamin Bonnier ; Anne Mockel ; Freddy Napora
• 刊名：Organic Process Research & Development
• 出版年：2006
• 出版时间：July 2006
• 年：2006
• 卷：10
• 期：4
• 页码：776 - 783
• 全文大小：143K
• 年卷期：v.10,no.4(July 2006)
• ISSN：1520-586X

文摘

Several novel approaches have been investigated for thesynthesis of the LTD₄/E₄ antagonist LY290154. Significantimprovements to the discovery route were first made by usingan indoline nucleophile instead of an indolyl anion in the keysubstitution step. An alternative approach, introducing the7-chloroquinoline moiety in the latest stages of the synthesiswas then demonstrated. Interestingly, the pivotal intermediateof this latter route was also obtained in a one-pot processfollowing a Katritzky methodology. Finally, an asymmetricsynthesis offering significant advantages over the enantioselective route reported by McKillop was demonstrated.