通过压力促进的分子内循环化合成 (-) - 劳沃明B
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Updated: Jun 19, 2025
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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
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Jake M Aquilina1, Ankush Banerjee1, Gabriel N Morais1,2
1Department of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390, United States.
Journal of the American Chemical Society
|July 23, 2024
概括
研究人员首次实现了 (-) - 劳沃B的全合成,这是一种具有环环的类. 该策略采用了四环N-硫基的分子内循环化,在11个步骤中产生向分子.
科学领域:
- 有机化学
- 自然产品合成
- 医学化学
背景情况:
- 印度醇化物是具有多种生物活性的一大类天然产品.
- (-) - 劳沃明B是一种不寻常的含有环的醇,其总合成尚未报告.
- 为了进一步研究和潜在的治疗应用,开发高效的合成途径对复杂的天然产品至关重要.
研究的目的:
- 实现第一个全合成的醇 (-) - 劳沃B.
- 开发一种以分子内循环化为中心的新合成策略.
- 通过计算研究调查影响关键环化步骤的因素.
主要方法:
- 合成采用了多步骤的方法,涉及催化立体特异性氨化.
- 关键反应包括 cis- 选择性皮克特- 斯勒反应和闭环转化,用于构建四环核.
- 最后一步涉及N- 硫基前体的分子内循环化.
主要成果:
- 在11个步骤中成功完成了 (-) - 劳沃B的总合成,总产量为2. 4%.
- 发现关键的分子内循环化步骤的效率高度依赖于前体的结构和形状应变.
- 进行了密度功能理论 (DFT) 研究以探索这种依赖的起源.
结论:
- 这项研究报告了第一个 (-) - 劳沃B的总合成,确定了这种复杂的天然产品的可行途径.
- 开发的策略突显了分子内环的有用性,用于构建含有环的化物.
- 计算洞察力为循环化反应中的立体化学结果提供了更深入的理解.
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