オーガノボロン製法によるパルメロリドAの触媒的非対称合成
Marlin Penner1, Vivek Rauniyar, Ludwig T Kaspar
1Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.
Journal of the American Chemical Society
|September 22, 2009
まとめ
研究者らは,海洋天然産物 (-) - パルメロリドAの触媒エナチオセレクティブ合成を達成しました. この新しいアプローチは,キラル補助物質とキラルプールを回避し,薬剤発見のための新しい戦略を提供します.
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:
- (-) - パルメロリドAのような海洋天然製品は,抗メラノーマ剤として有望なことを示しています.
- 効率的でエナチオセレクティブな合成経路は,さらなる研究と薬の開発のためにこれらの複雑な分子にアクセスするために不可欠です.
- 既存の合成戦略は,時間がかかり,持続可能性が低い方法に依存する可能性があります.
研究 の 目的:
- (-) - パルメロライドA.の新しい,触媒的なエナンチオセレクティブ合成を開発する.
- ステキオメトリックキラル補助体とキラルプールを回避する戦略を策定する.
- 複雑な天然製品ターゲットに適用できる新しい合成方法論を探求する.
主な方法:
- 21段階の合成シーケンスが採用されました.
- 仮面化ヒドロキシル群としてアルケニルボロナートを使用した新しいクライゼン-アイルランド再配列が,分子右半分のために使用されました.
- ダイオール.SnCl(4) -触媒化されたエナチオセレクティブクロチルボレーションは,左半球の複合標的合成で初めて適用されました.
主要な成果:
- (-) - パルメロリドAの触媒エナチオセレクティブ合成が成功しました.
- この合成は,新しいクライゼン-アイルランド再配置変数の有用性を実証した.
- この研究は,複合合成におけるダイオール.SnCl(4) -触媒化されたエナチオセレクティブクロチルボレーションの最初の応用を示した.
結論:
- (-) - パルメロリドAへの新しい効率的な合成経路が確立されています.
- 策定された戦略は,複雑な海洋天然製品にアクセスするための強力なツールを提供します.
- この独特な合成アプローチは,単純化され,潜在的により強力なパルメロリド類のアナログの設計を容易にする可能性があります.
関連する概念動画
03:08Hydroboration-Oxidation of Alkenes
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
Introduction
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
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.
01:15α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction
The method to achieve α-brominated carboxylic acids using a mixture of phosphorus tribromide and bromine is known as the Hell–Volhard–Zelinski reaction. The reaction is catalyzed by phosphorus tribromide, which can be used directly or produced in situ from red phosphorus and bromine. The mechanism comprises PBr3 catalyzed conversion of acid to acid bromide and hydrogen bromide. The acid bromide enolizes to its enol form in the presence of HBr. The nucleophilic enol attacks the bromine molecule...
01:27Radical Substitution: Allylic Bromination
In organic synthesis, the formation of products can be altered by changing the reaction conditions. For example, a dibromo addition product is formed when propene is treated with bromine at room temperature. In contrast, propene undergoes allylic substitution in non-polar solvents at high temperatures to give 3-bromopropene. In order to avoid the addition reaction, the bromine concentration must be kept as low as possible throughout the reaction. This can be achieved using N-bromosuccinimide...
02:15Preparation of Alcohols via Addition Reactions
Overview
The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation...
The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation...