针对独特的pederin家族成员psymberin的研究:全面阐明结构,两个替代的总合成,以及类似物
Yu Feng1, Xin Jiang, Jef K De Brabander
1Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, USA.
Journal of the American Chemical Society
|September 26, 2012
概括
开发了两条合成路径到psymberin,证实它与irciniastatin A相同. 这项研究为了解psymberin提供了基础.
科学领域:
- 有机合成 有机合成
- 药用化学 医学化学
- 化学生物学 化学生物学
背景情况:
- 柏林是一种复杂的海洋天然产品,具有潜在的生物活性.
- 以前的合成努力是有限的,阻碍了进一步的研究.
- psymberin和irciniastatin A之间的结构关系尚不清楚.
研究的目的:
- 为了实现psymberin的总合成.
- 为了确认psymberin和irciniastatin A.的身份.
- 为模拟合成开发一种灵活的合成策略,以帮助理解psymberin的化学生物学.
主要方法:
- 对第一代和第二代都采用了融合合成策略.
- 关键反应包括二聚选择性阿尔多尔合,一种新型的一胺转化为N-氨酸氨基的新型转化,催化酶选择性双化,以及索诺加希拉合/循环异构/还原序列.
- 合成涉及准备三个关键片段.
主要成果:
- 在17-18个步骤中,成功完成了两条截然不同的合成路径到psymberin.
- 合成证实了psymberin和irciniastatin A是相同的化合物.
- 合成了足够数量的psymberin (~0.5g),用于进一步的生物研究.
- 合成了一种psymberin-pederin杂交物 (psympederin) 和其他类似物.
结论:
- 实现了psymberin的总合成,建立了它的结构和身份.
- 开发的合成路径高效且融合,使得模拟合成成为可能.
- 合成和模拟研究为了解psymberin和相关化合物的化学生物学提供了基础.
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