通过以氧化为基础的 [5 + 2] 循环添加,对海纳诺利多尔和哈林格托诺利德进行立体选择性总合成
Min Zhang1, Na Liu, Weiping Tang
1School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705, USA.
Journal of the American Chemical Society
|August 13, 2013
概括
研究人员开发了一种新的合成途径,用于构建海纳诺利多尔和哈林诺利德的复杂碳骨架. 这种高效的方法利用氧化酸循环添加和环开放策略来合成天然产品.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 自然产品的合成自然产品的合成
背景情况:
- 海纳诺利多尔和哈林诺利德是具有潜在生物活性的复杂天然产品.
- 需要有效的合成策略来访问这些具有挑战性的分子架构.
研究的目的:
- 开发一种有效的合成路径,用于海纳诺利多尔和哈林诺利德的四环碳骨架.
- 在有机合成中探索新的循环添加和环开放方法.
主要方法:
- 基于氧化的内分子 [5 + 2] 循环添加,用于骨架结构.
- 在8-oxabicyclo[3.2.1]octenes中,以太桥断裂的阳离子环开放策略.
- 顺序的 [4 + 2] 循环添加,Kornblum-DeLaMare 重组,并对循环他二烯的双重消除转化为子.
主要成果:
- 对海纳诺利多尔和哈林诺利德四环碳骨架的高效构建.
- 开发一种新的策略,用于在自行车系统中切割以太桥梁.
- 使用多步序列,成功地将环乙转化为热.
- 证实了从海纳诺利多尔中生物仿真合成哈林诺利德的结果.
结论:
- 开发的合成策略提供了一条有效的途径,以hainanolidol和harringtonolide.
- 新的方法扩大了复杂天然产品合成的工具包.
- 这项研究强调了循环添加和重排反应在构建复杂的分子框架中的力量.
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
相关概念视频
02:44Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
01:16Cycloaddition 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.
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
01:27Cyclohexenones 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).
![[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2Ffiles%2Fmedia%2Fscience-education%2Fscience-education-thumbs%2F12417.jpg&w=3840&q=75)
01:16[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
02:04Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.