通过编程的激素级联合成一种ophiobolin sesterterpene
Zachary G Brill1, Huck K Grover1, Thomas J Maimone2
1Department of Chemistry, University of California, Berkeley, 826 Latimer Hall, Berkeley, CA 94702, USA.
概括
研究人员开发了一种新的激素循环化方法来合成复杂的烯,克服了天然产品合成的挑战. 这种方法有效地创造了化环系统,并使细胞毒性化合物的总合成成为可能.
科学领域:
- 有机化学
- 自然产品合成
- 医学化学
背景情况:
- 循环酶通过聚烯链循环自然合成复杂的烯.
- 这些复杂的多环结构的非生物合成仍然具有挑战性.
- 类是具有药用意义的一类重要的天然产品.
研究的目的:
- 开发一种使用激素循环的复杂的新合成策略.
- 有效地构建许多自然产品的5-8-5化环系统.
- 通过特定的ophiobolin sesterterpene的总合成来证明这种方法的实用性.
主要方法:
- 使用激素,而不是阴离子的反应途径,以循环化先衍生链.
- 采用一个减少的激素级循环.
- 研究小分子硫醇催化剂对二聚体选择性的影响.
主要成果:
- 有效地形成复杂的5-8-5化环系统.
- 成功完成了9个步骤的 (-) -6 -epi-ophiobolin N的总合成.
- 证明硫醇催化剂可以在激素级循环中覆盖固有的二重选择性.
结论:
- 开发的激素循环化策略为复杂的环系统提供了有效的途径.
- 这种方法为药物研究提供了具有历史挑战性的天然产品.
- 这些发现为合成具有潜在治疗用途的多种特素奠定了基础.
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