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Updated: Jul 9, 2026
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Determination of the Gas-phase Acidities of Oligopeptides
Published on: June 24, 2013
カリペルトシドa:全合成,絶対的および相対的構成の割り当て,合成アナログの評価
Barry M Trost1, Janet L Gunzner, Olivier Dirat
1Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA.
Journal of the American Chemical Society
|August 29, 2002
まとめ
抗腫瘍剤カルリペルトシドAおよび同類物の全合成が完了し,その立体化学が確立されました. この研究は,糖分分子を強調して,構造-活動関係に関する洞察を提供します.
科学分野:
- オーガニック・シンセシス オーガニック・シンセシス
- 薬用化学 薬用化学について
- 化学生物学 化学生物学とは
背景:
- カリペルトゾイドAは,未指定の立体化学を持つ新しい抗腫瘍剤です.
- 構造-活性関係 (SAR) を理解することは,効果的ながん治療法の開発に不可欠です.
研究 の 目的:
- カリペルトシドAおよびその類似体の全合成を達成するために.
- カリペルトシドAの以前に確立されていないステレオ化学を割り当てるために.
- カリペルトソイドAのSARを調査し,その構造成分の役割に焦点を当てました.
主な方法:
- 融合合成戦略を用いて,マクロラクトン,カリペルトーゼ糖,サイクロプロピルを含む鎖という3つの主要な単位に分解した.
- 主要な反応には,ダイアステロ選択性アルドール反応,CBS-オキサボロリジンによるケトン還元,パラジウム触媒による非対称性アリルアルキレーション (AAA),アルケン-アルキン結合,ルテニウム触媒によるオレフィン合成,アシルケテンによるマクロラクトニゼーション,O-トリクロアセチミデートによるグリコシル化が含まれていた.
- サイドチェーンの結合のために,新しいワンポットオレフィンメタテシス-タカイオレフィネーションプロトコルが開発されました.
主要な成果:
- カリペルトソイドAといくつかの類似体の全合成が成功しました.
- カリペルトソイドAのステレオ化学は,C-20 (S) とC-21 (R) の構成を含む,決定的に割り当てられました.
- この合成により,マクロラクトンのC-13エピマーとトランスクロクロクロプロパンダイアステロエーマーの両方にアクセスが可能になった.
結論:
- マクロラクトンへの16段階の経路を持つコンバージェント合成は,SAR研究に適しています.
- 初期生物学的試験では,塩素置換剤は活性に欠かせないが,砂糖分は決定的であることが示されている.
- 開発された合成方法論,特にルテニウム触媒プロセスとワンポットオレフィネーションプロトコルは,広範な適用性を提供します.
関連する概念動画
02:29Relative Strengths of Conjugate Acid-Base Pairs
Brønsted-Lowry acid-base chemistry is the transfer of protons; thus, logic suggests a relation between the relative strengths of conjugate acid-base pairs. The strength of an acid or base is quantified in its ionization constant, Ka or Kb, which represents the extent of the acid or base ionization reaction. For the conjugate acid-base pair HA / A−, the ionization equilibrium equations and ionization constant expressions are
01:15Carboxylic Acid Derivatives: Overview
Carboxylic acid derivatives are formed by replacing the hydroxyl group of carboxylic acids with a different functional group. The most common carboxylic acid derivatives are:
01:25Acidity and Basicity of Carboxylic Acid Derivatives
Carboxylic acids are the strongest among organic acids, as they readily lose the hydroxyl proton to form a resonance-stabilized carboxylate ion. In comparison, the acid derivatives lack acidic hydrogens directly attached to a functional group. In these compounds, the acidic nature arises from their ability to lose α hydrogens, making them weakly acidic.
The relative acidic strength of the derivatives can be explained based on the extent of resonance stabilization of the conjugate base. The...
The relative acidic strength of the derivatives can be explained based on the extent of resonance stabilization of the conjugate base. The...
01:13Relative Reactivity of Carboxylic Acid Derivatives
Carboxylic acid derivatives such as acid halides, anhydrides, esters, and amides undergo nucleophilic acyl substitution reactions with varying degrees of reactivity.
A key factor in assessing the reactivity of the acid derivatives is the basicity of the substituent or the leaving group. The lower the basicity of the leaving group, the higher the reactivity of the derivative. The basicity of the leaving group follows this order:
Halide ions < Acyloxy ions < Alkoxy ions < Amine ions
A key factor in assessing the reactivity of the acid derivatives is the basicity of the substituent or the leaving group. The lower the basicity of the leaving group, the higher the reactivity of the derivative. The basicity of the leaving group follows this order:
Halide ions < Acyloxy ions < Alkoxy ions < Amine ions
01:23Complexation Equilibria: Overview
Complexation reactions take place when dative or coordinate covalent bonds form between metal ions and ligands. The compounds formed in these reactions are called coordination compounds. The number of bonds formed between the metal ion and the ligands is called its coordination number. Generally, most metal ions in an aqueous solution are solvated by water molecules and thus exist as aqua complexes.
The equilibrium constant of the complexation reaction is represented as the formation constant...
The equilibrium constant of the complexation reaction is represented as the formation constant...
01:19Composition of Polyprotic Acid Solutions as a Function of pH
Polyprotic acids of the type H2M constitute two ionizable protons. As a result, on titration with a base, they exhibit two equivalence points in the titration curve. During titration, the species H2M, HM−, and M2− will be present in the solution at different points. The fractions of H2M, HM−, and M2− present at the various instances of the titration are denoted by α0, α1, and α2, respectively.
A graph with the alpha values is plotted against the volume of base added during titration. Here, a...
A graph with the alpha values is plotted against the volume of base added during titration. Here, a...