酸化したウェルウィットインドリノーンと (-) -N-メチルウェルウィットインドリノーンCイソニトリルCの総合成
Kyle W Quasdorf1, Alexander D Huters, Michael W Lodewyk
1Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
Journal of the American Chemical Society
|January 13, 2012
まとめ
研究者らは,複合的な天然製品, (-) -N-メチルウェルウィットインドリノンのCアイソニトリルおよび3酸化水素化されたウェルウィットインドリノンの全合成を達成しました. デウテリウムの運動同位体効果は,重要なニトロンの挿入反応を強化し,合成効率を改善しました.
科学分野:
- 有機化学 オーガニック・ケミストリー
- 自然製品合成 自然製品の合成
- 薬用化学 薬用化学について
背景:
- Welwitindolinonesは,潜在的な生物学的活動を持つ難解な海洋天然製品のクラスです.
- 以前の合成の取り組みは限られたもので,効率的なルートが必要であることを強調しています.
研究 の 目的:
- (-) -N-メチルウェルウィットインドリノンCイソニトリルの最初の完全合成を報告する.
- 3-ヒドロキシル化ウェルウィチン・インドリノンの合成経路を開発する.
- 自然製品の合成における運動性同位体効果の有用性を調査する.
主な方法:
- 戦略的なデウテリウム運動同位体効果を利用した総合成.
- 後期ナイトレン挿入反応の最適化.
- ステレオ化学の計算による予測.
- 立体化学的構成の実験的確認.
主要な成果:
- (-) -N-メチルウェルウィットインドリノンのCアイソニトリルの完全な合成が成功しました.
- 3-ヒドロキシル化ウェルウィチン・インドリノンの効率的な合成が達成されました.
- デウテリウムの運動同位体効果により,ニトロンの挿入効率が著しく改善されました.
- 計算および実験的研究により,C3のステレオ化学が確認されました.
結論:
- 開発された合成戦略は,重要な天然製品へのアクセスを提供します.
- 動的同位体効果の使用は,複雑な合成ステップを最適化するための強力なツールを提供します.
- この研究は,天然産物合成の分野を発展させ,さらなる生物学的評価のための化合物を提供します.
関連する概念動画
01:14Aldehydes and Ketones to Alkenes: Wittig Reaction Mechanism
The Wittig reaction, which converts aldehydes or ketones to alkenes using phosphorus ylides, proceeds through a nucleophilic addition‒elimination process.
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...
01:19Aldehydes and Ketones to Alkenes: Wittig Reaction Overview
The Wittig reaction is the conversion of carbonyl compounds-aldehydes and ketones-to alkenes using phosphorus ylides, or the Wittig reagent. The reaction was pioneered by Prof. Georg Wittig, for which he was awarded the Nobel Prize in Chemistry.
01:19Nitrosation of Enols
The nitrosation reaction is one of the methods of preparing 1,2-diketones. The enol tautomer of the starting ketone reacts with sodium nitrite in hydrochloric acid, generating the 1,2-diketone after hydrolysis.
01:32Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview
Cyanohydrins are compounds that contain –CN and –OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction mixture.
03:00Preparation 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...
01:12Preparation of Nitriles
One of the common methods to prepare nitriles is the dehydration of amides. This method requires strong dehydrating agents like phosphorous pentoxide or boiling acetic anhydride for converting amides to nitriles. Another reagent namely, thionyl chloride also accomplishes the dehydration of amides, where amide acts as a nucleophile. The first step of the mechanism involves the nucleophilic attack by the amide on the thionyl chloride to form an intermediate. In the next step, the electron pairs...