ハイアノリドールとハリントノリドのステレオ選択的全合成は,オキシドピリウムベースの [5 + 2] サイクル添加による
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
まとめ
研究者たちは,ハイナノリドールとハリントノリドルの複雑な炭素骨格を構築するための新しい合成経路を開発しました. この効率的な方法は,オキシドピリリウムサイクロアディションと環開き戦略を天然製品合成に使用しています.
科学分野:
- 有機化学 オーガニック・ケミストリー
- 合成化学 合成化学とは
- 自然製品合成 自然製品合成
背景:
- ハイアノリドールとハリントノリドは,潜在的な生物学的活動を持つ複雑な天然製品です.
- これらの複雑な分子構造へのアクセスには,効率的な合成戦略が必要である.
研究 の 目的:
- ハイアノリドールとハリントノリドルのテトラサイクル炭素骨格のための効率的な合成経路を開発する.
- 有機合成における新しいサイクル添加とリング開封の方法論を探求する.
主な方法:
- 骨格構造のための分子内酸化ピリリウムベースの [5 + 2] サイクロアディション.
- 8-オキサビサイクロ[3.2.1]オクテネスにおけるエーテルブリッジ割れのためのアニオン環開き戦略.
- 連続 [4 + 2] サイクロアディション,コーンブルム-デラマール再配列,サイクロヘプタディエンのトロポン変換への二重除去.
主要な成果:
- ハイアノリドールとハリントノリドのテトラサイクル炭素骨格の効率的な構築.
- 自転車システムにおけるエーテルブリッジの分割のための新しい戦略の開発.
- 多段階の配列を用いて,サイクロヘプタディエンのトロポンへの成功変換.
- ハイアノリドールからハリントノリドのバイオミメティック合成の確認.
結論:
- 開発された合成戦略は,ハイナノリドールとハリントノリドへの効率的な経路を提供します.
- 新しい方法論は,複雑な天然製品合成のためのツールキットを拡張します.
- この研究は,複雑な分子構造の構築におけるサイクル添加および再配置反応の力を強調しています.
![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)
関連する概念動画
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.