总合成 (+/-) - 和 (-) - 乙氨基酸
Connor L Martin1, Larry E Overman, Jason M Rohde
1Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, USA.
Journal of the American Chemical Society
|March 12, 2010
概括
使用关键的aza-Cope/Mannich反应开发了 (+/-) -actinophyllic acid和 (-) -actinophyllic acid的有效总合成,以构建六环原子核. 第二代合成简洁,在几个步骤中实现高产量.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 自然产品的合成自然产品的合成
背景情况:
- 动氨基酸是一种复杂的天然产品,具有独特的六环环系统.
- 之前的合成路径到actinophyllic acid并没有完全建立或有效.
- 阿扎-科普/曼尼克反应是构建复杂的含环系统的强大工具.
研究的目的:
- 开发一种高效的全合成方法,既可用于种族性,又可用于纯乙烯酸乙烯酸.
- 为了利用aza-Cope/Mannich反应来构建六环核的关键步骤.
- 探索一种简化和简洁的合成策略,用于酸.
主要方法:
- 从o-nitrophenylacetic酸中组装一个四环基前体 (rac-37).
- 应用aza-Cope/Mannich反应,形成一个五环基中间体 (rac-44).
- 精简的第二代合成涉及β-基中间体 (rac-53).
- 使用催化式对α,β不和子的选择性降解进行的选择性合成 (66).
主要成果:
- 成功开发了 (+/-) - 乙酸和 (-) - 乙酸的高效总合成方法.
- 阿扎-科普/曼尼克反应有效地在单个步骤中构建了六环环系统.
- 第二代合成 (+/-) - 乙烯基酸在六个步骤中实现了22%的总产量.
- 完成了第一个对 (-) - 乙氨基酸的选择性合成.
结论:
- 开发的合成序列可以有效地获取actinophyllic acid及其酶体.
- 阿扎-科普/曼尼克反应是构建复杂的活性酸骨架的关键转换.
- 这项研究强调了aza-Cope/Mannich反应在 (-) -actinophyllic acid的生物合成中的潜在参与.
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