ポリエーテル・ラサロシドのバイオシンセシスに関与する配列酵素エポキシデーション
Atsushi Minami1, Mayu Shimaya, Gaku Suzuki
1Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan.
Journal of the American Chemical Society
|April 18, 2012
まとめ
フラビンを含むモノオキシゲナーゼ (FMO) は,ラサロシドのようなポリエーテル骨格の構築における重要なステップであるエナチオセレクティブエポキシデーションを触媒化する. この研究は,ポリエーテル生物合成の酵素機構を明らかにしています.
科学分野:
- バイオケミストリー バイオケミストリー
- 有機化学 オーガニック・ケミストリー
- 分子生物学は分子生物学である.
背景:
- ポリエーテル骨格は,イオノフォールポリエーテルなどの天然製品において極めて重要です.
- エナチオセレクティブエポキシデーションとレジオセレクティブエポキシド開口は,重要な合成ステップです.
- フラビンを含むモノオキシゲナーゼ (FMO) は,ポリエーテル生物合成における酸化のための潜在的な酵素である.
研究 の 目的:
- ポリエーテルラサロシドの生物合成におけるFMOであるLSD18の役割を調査する.
- ポリエーテル構造におけるエナチオセレクティブエポキシデーションの酵素メカニズムを理解する.
主な方法:
- Lsd18酵素のインビボおよびインビトロ分析.
- 単純なオレフィンと断片化されたダイエンを含む基板ミミカーの使用.
- エポキシデーション製品の特性.
主要な成果:
- Lsd18はエナチオセレクティブエポキシデーションを段階的に行う.
- 酵素は天然型のモノまたはビスエポキシドを生成する.
- ラサロシドポリエーテル生物合成におけるFMOの関与を証明した.
結論:
- Lsd18はフラビンを含むモノオキシゲナーゼで,ラサロシド生物合成に不可欠です.
- この研究は,ポリエーテル骨格の構築のための酵素経路を明確にします.
- 段階的なエナチオセレクティブエポキシデーションメカニズムについての洞察を提供します.
関連する概念動画
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...
02:26Base-Catalyzed Ring-Opening of Epoxides
Due to their highly strained structures, epoxides can readily undergo ring-opening reactions through nucleophilic substitution, either in the presence of an acid or a base. The nucleophilic substitution reactions in the presence of acid are called acid-catalyzed ring-opening reactions, and nucleophilic substitution reactions in the presence of a base are called base-catalyzed ring-opening reactions. Epoxides undergo base-catalyzed ring-opening reactions in the presence of a strong nucleophile...
02:24Acid-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...
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.
02:57Sharpless Epoxidation
The conversion of allylic alcohols into epoxides using the chiral catalyst was discovered by K. Barry Sharpless and is known as Sharpless epoxidation. The use of a chiral catalyst enables the formation of one enantiomer of the product in excess. This chiral catalyst is mainly a chiral complex of titanium tetraisopropoxide and tartrate ester (specific stereoisomer). The stereoisomer used in the chiral catalyst dictates the formation of the enantiomer of the product. In other words, the use of...
02:38Structure and Nomenclature of Epoxides
Cyclic ethers are heterocyclic compounds with an oxygen atom in the ring along with carbon atoms. They are named depending on the number of carbon atoms present in their ring system. Cyclic ethers with a three-membered ring system are called “oxirane”, four-membered ring systems as “oxetane”, five-membered ring systems as “oxolane”, and six-membered ring systems as “oxane”. The cyclic structure of these rings imposes angle strain, and this strain is more in the ring having a smaller number of...