一个简短的路径,通过 ynolides 化的宏: 循环二二
Zhi-Qiang Yang1, Samuel J Danishefsky
1Laboratory for Bioorganic Chemistry, Sloan Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
Journal of the American Chemical Society
|August 9, 2003
概括
一种新的合成方法产生了cycloproparadicicol,它是一种强大的纳米分子热冲击蛋白90 (Hsp90) 抑制剂. 这一突破利用了复合和双重的迪尔斯-阿尔德反应,以高效地组装巨乳素.
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:
- 热冲击蛋白90 (Hsp90) 是癌症的一个关键治疗点.
- 赛克洛帕拉迪西科尔是一种强大的Hsp90抑制剂,具有纳米分子活性.
- 复杂的天然产品的高效合成对于药物开发至关重要.
研究的目的:
- 开发一种易于和高效的合成循环基醇.
- 探索复杂的巨乳结构的新型合成策略.
主要方法:
- 复合促进了环闭性转化 (RCM).
- 双重的迪尔斯-阿尔德/复古的迪尔斯-阿尔德反应.
- 复醇麦克罗拉克核的组装.
主要成果:
- 在纳米分子产量中成功合成了环二二醇 (2).
- 展示一种结合RCM和Diels-Alder反应的新型合成路径.
- 复杂的麦克罗拉克顿脚手架的高效建造.
结论:
- 开发的合成路径提供了一个易于访问的cycloproparadicicol.
- 这种方法为合成相关的麦克罗拉克化合物提供了有价值的策略.
- 合成突出了催化RCM在复杂分子结构中的实用性.
相关概念视频
Cycloaddition Reactions: Overview
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1
Treating arylamines with nitrous acid gives aryldiazonium salts that are effective substrates in nucleophilic aromatic substitution reactions. The diazonio group in these salts can be easily displaced by different nucleophiles, yielding a wide variety of substituted benzenes. The leaving group departs as nitrogen gas, and this easy elimination is the driving force for the substitution reaction.
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo, or cyano...
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo, or cyano...
Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper...
Alkylation of β-Diester Enolates: Malonic Ester Synthesis
Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Robinson annulation is a base-catalyzed reaction for the synthesis of 2-cyclohexenone derivatives from 1,3-dicarbonyl donors (such as cyclic diketones, β-ketoesters, or β-diketones) and α,β-unsaturated carbonyl acceptors. Named after Sir Robert Robinson, who discovered it, this reaction yields a six-membered ring with three new C–C bonds (two σ bonds and one π bond).
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Diels–Alder reactions between cyclic dienes locked in an s-cis configuration and dienophiles yield bridged bicyclic products.

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