peracid酸化によって開始されたナザロフサイクル: (+/-) -ロカグラミドの全合成
John A Malona1, Kevin Cariou, Alison J Frontier
1Department of Chemistry, University of Rochester, Rochester, New York 14627, USA.
Journal of the American Chemical Society
|May 19, 2009
まとめ
研究者はアグラフォリン,ロカグロ酸,ロカグラミドの総合成を達成しました. この新しいアプローチは,ナザロフサイクリングとオキシカルベニウムイオンの中間体を使用して,効率的でダイアステロセレクティブな合成を行います.
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
背景:
- ロカグラミドとその類型は,重要な生物学的活動を持つ天然製品です.
- ロカグラミドおよび関連する化合物への以前の合成経路は,効率とステレオ選択性の限界があります.
研究 の 目的:
- アグラフォリン,ロカグロ酸,ロカグラミドの新しく効率的な全合成を開発する.
- これらの天然製品のコア構造を構築するナザロフサイクライゼーションの有用性を探求する.
主な方法:
- ナザロフサイクライゼーションを用いた総合成.
- アレノールエーターのペラシド酸化によるオキシアリルカチオン中間物の生成.
- 珍しいオキシカルベニウムイオン種の形成.
主要な成果:
- アグラフォリン,ロカグロ酸,ロカグラミドの成功的かつ効率的な全合成が達成されました.
- 合成経路は高度にダイアステレオセレクティブであり,最終製品のステレオ化学を制御します.
- 以前のロカグラミド合成とは異なる新しい戦略が確立されました.
結論:
- 記述された合成戦略は,ロカグラミドおよび関連する天然製品への新しい効果的な経路を提供します.
- ナザロフサイクライゼーションと生成されたオキシカルベニウムイオン中間物質の使用は,合成方法論の重要な進歩を表しています.
関連する概念動画
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).
Preparation of 1° Amines: Gabriel Synthesis
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...
Oxidation 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.
Preparation of Epoxides
Overview
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
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Some cycloaddition reactions are activated by heat, while others are initiated by light. For example, a [2 + 2] cycloaddition between two ethylene molecules occurs only in the presence of light. It is photochemically allowed but thermally forbidden.
Preparation of Carboxylic Acids: Carboxylation of Grignard Reagents
Carboxylic acids can be prepared by the carboxylation of Grignard reagents (RMgX). This method is convenient for converting alkyl (primary, secondary or tertiary), vinyl, benzyl, and aryl halides to carboxylic acids with one additional carbon than the starting RMgX.
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