(-) - 希马伦辛A的总合成
Heyao Shi1, Iacovos N Michaelides1, Benjamin Darses1
1Department of Chemistry, Chemistry Research Laboratory, University of Oxford , Mansfield Road, Oxford, OX1 3TA, U.K.
Journal of the American Chemical Society
|November 10, 2017
概括
研究人员使用22步的过程首次实现了 (-) - 希马伦辛A的选择性合成. 关键步骤包括用于核心构建的新型催化级联和用于环形成的激素循环,从而产生天然产品.
科学领域:
- 有机化学
- 合成化学
- 自然产品合成
背景情况:
- (-) - 希马伦辛A是一种复杂的天然产品,具有独特的五环结构.
- 之前的合成努力未能实现对该分子的反选择性路径.
- 开发复杂化合物的高效合成策略对于化学生物学和药物发现至关重要.
研究的目的:
- 实现第一个对 (-) - 希马伦辛A的选择性总合成.
- 开发适用于复杂天然产品合成的新型合成方法.
- 探索用于高效构建多环框架的新级联反应.
主要方法:
- 使用一种新型的催化,选择性原型转移/迪尔斯-阿尔德 (IMDAF) 级联反应来构建ACD三环核.
- 为了组装B环,使用了还原性激素循环级联.
- 关键的终端转换包括分子氧介导的 γ-CH 氧化,斯特特循环化和化学选择性乳酸减少.
主要成果:
- 在22个步骤中成功完成了第一个对 (-) - 希马伦辛A的选择性合成.
- 开发的IMDAF布为核心三环结构提供了有效的途径.
- 这一序列的高潮是自然产品的立体控制形成.
结论:
- (-) - 希马伦辛A的总合成表明了复杂分子结构中的级联反应的力量.
- 开发的合成途径为获得类似物和研究海马类化合物的生物活性提供了宝贵的平台.
- 这项工作扩大了合成化学家应对挑战性的天然产品目标的工具包.
相关概念视频
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
3.9K
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
3.9K
Combined Effects of Drugs: Synergism
7.0K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
7.0K
Amines to Sulfonamides: The Hinsberg Test
4.5K
The Hinsberg test is a method to identify primary, secondary and tertiary amines, named after its pioneer, Oscar Hinsberg. Here, amines are treated with benzenesulfonyl chloride, also known as the Hinsberg reagent, in the presence of an excess of aqueous base, followed by acidification. Based on the nature of the amines, different changes are observed.
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing sulfonyl...
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing sulfonyl...
4.5K
Preparation of 1° Amines: Gabriel Synthesis
4.7K
Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
4.7K


