シドモミン生物合成におけるN-O-C結合形成のための潜在的オクサゾリン電解体
Elizabeth S Sattely1, Christopher T Walsh
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Journal of the American Chemical Society
|August 20, 2008
まとめ
偽モニン (pseudomonine) とは,偽モニン (pseudomonine) と呼ばれるものです.
科学分野:
- バイオケミストリー バイオケミストリー
- 自然製品のバイオシンセシス
- 有機化学 オーガニック・ケミストリー
背景:
- 窒素-ヘテロ原子結合は,天然製品の多様性にとって極めて重要です.
- Pseudomonineは,Pseudomonas siderophoreであり,N-Oヒドロキサート結合を持つユニークなイソキサゾリジノンリングを特徴としています.
- このようなユニークなヘテロサイクルの生体発生を理解することは不可欠です.
研究 の 目的:
- pseudomonineにおけるイソザゾリジノン環の生物合成経路を解明する.
- 偽モニン合成酵素の特徴を述べる.
- 自然製品バイオシンセシスにおける新種のヘテロサイクリング方法を調査する.
主な方法:
- 偽モミン合成酵素のインビトロ特性.
- 完全なシドモミン生物合成経路の復元.
- 反応中介物質と反応産物の分析.
主要な成果:
- シドモミニンのイソザゾリジノン環は,オクサゾリン前駆体の自発的な再配置によって形成されます.
- これは,組み立て直後のヘテロサイクリングのこれまで特徴づけられていないモードを表しています.
- この過程で,ヒドロキサマート機能の酸素原子が核愛者として作用する.
結論:
- この研究は,自然界におけるN-O-C結合形成の新たなメカニズムを明らかにしている.
- この発見は,天然製品の生合成とヘテロサイクルの形成に関する私たちの理解を広げています.
- 特定された経路は,合成化学と薬物の発見のための戦略を伝える可能性があります.
関連する概念動画
Nitrosation 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.
Enolate Mechanism Conventions
When a carbonyl compound is treated with a strong base, the α position gets deprotonated to give a resonance-stabilized intermediate called an enolate. Enolates are ambident nucleophiles because they possess two nucleophilic sites that can attack an electrophile owing to the delocalization of the negative charge between the α carbon and oxygen atoms. When the oxygen atom attacks an electrophile, it is called O-attack, whereas electrophilic attack via the α carbon is known as C-attack.
C-attack...
C-attack...
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...
Oxidative Cleavage of Alkenes: Ozonolysis
In ozonolysis, ozone is used to cleave a carbon–carbon double bond to form aldehydes and ketones, or carboxylic acids, depending on the work-up.
Ozone is a symmetrical bent molecule stabilized by a resonance structure.
Ozone is a symmetrical bent molecule stabilized by a resonance structure.
Regioselective Formation of Enolates
As depicted in the figure below, the unsymmetrical ketones can form two possible enolates: less substituted or more substituted enolates. Usually, the thermodynamic enolates are formed from the more substituted α-carbon atom, while the kinetic enolates are formed faster by deprotonation from the less substituted position. The thermodynamic enolates have lower energy, so they are more stable. But the energy required to form kinetic enolates is less.
Acid-Catalyzed Ring-Opening of Epoxides
Epoxides that are three-membered ring systems are more reactive than other cyclic and acyclic ethers. The high reactivity of epoxides originates from the strain present in the ring. This ring strain acts as a driving force for epoxides to undergo ring-opening reactions either with halogen acids or weak nucleophiles in the presence of mild acid. The acid catalyst converts the epoxide oxygen, a poor leaving group, into an oxonium ion, a better leaving group, making the reaction feasible. The...


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