"ボロノ-スクラレオリド"によるメロテルペノイドのスケーラブルで分散した合成
Darryl D Dixon1, Jonathan W Lockner, Qianghui Zhou
1Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|May 16, 2012
まとめ
研究者らは,新しい前駆体であるボロノ-スクラレオリドを使用して,生物活性メロテルペノイドのスケーラブルな合成を開発しました. この方法により, (+) -クロマゾナロールと,重要な生物学的活性を持つ関連化合物を大規模に生産することができます.
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
- 自然製品合成 自然製品合成
背景:
- メロテルペノイドは,多様な生物学的活動を持つ自然製品のクラスです.
- メロテルペノイドへのスケーラブルで効率的な合成経路の開発は,そのさらなる研究と応用に不可欠です.
研究 の 目的:
- 生物活性メロテルペノイドのスケーラブルで異なる合成戦略を開発する.
- 効率的な合成のために,新しいテルペニルラジカル前駆体を導入する.
主な方法:
- 重要なテルペニル基の前駆体としての"ボロノ・スクラレオリド"の発明.
- (+) -クロマゾナロールのグラムスケール製剤を可能にするスケーラブルな合成経路の開発.
- 関連メロテルペノイドにアクセスするための重要な中間物質の後の合成改変.
主要な成果:
- メロテルペノイドのスケーラブルで分散した合成の成功開発.
- (+) -クロマゾナロールのグラムスケール製剤が達成されました.
- 潜在的な生物学的活性を持つ様々な関連メロターペノイドへの迅速なアクセス.
結論:
- 開発された合成戦略は,メロテルペノイドの生産に有効です.
- 新型ボロノ・スクラレオリド前駆体は,効率的でスケーラブルな合成を容易にする.
- この方法論は,潜在的な治療用途を持つ化合物へのアクセスを提供します.
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.
02:36Regioselectivity 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.
01:29Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Diels–Alder reactions between cyclic dienes locked in an s-cis configuration and dienophiles yield bridged bicyclic products.
![[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2Ffiles%2Fmedia%2Fscience-education%2Fscience-education-thumbs%2F12417.jpg&w=3840&q=75)
01:16[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
01:18β-Dicarbonyl Compounds via Crossed Claisen Condensations
Crossed Claisen condensations are base-promoted reactions between two different ester molecules producing β-dicarbonyl compounds. The reaction involving esters, with both containing α hydrogen, results in a mixture of four different products that are difficult to isolate. This reduces the synthetic utility of the reaction.
01:27Cyclohexenones 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).