形成纳税的碳酸级联形成纳税.
Young J Hong1, Dean J Tantillo
1Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, United States.
Journal of the American Chemical Society
|October 13, 2011
概括
量子化学计算揭示了来自geranylgeranyl diphosphate的taxadiene生物合成的完整途径. 这项机制性研究澄清了碳酸介质构造,并提出了taxadiene synthase中的基质模拟物的一种非生产性结合方向.
科学领域:
- 生物化学 生物化学
- 计算化学计算化学
- 有机化学 有机化学
背景情况:
- 塔克萨迪因是抗癌药物帕克利塔塞尔的前体.
- 纳税的生物合成涉及复杂的碳酸重排.
- 之前的taxadiene合成酶的机制性建议是基于有限的实验数据.
研究的目的:
- 通过量子化学计算,阐明使用taxadiene生物合成的完整反应途径.
- 将理论发现与现有实验数据相协调,包括标记研究.
- 提出对纳税合成酶内的基质类型具有约束力的指导方针.
主要方法:
- 量子化学计算被用来确定中间体和过渡状态的结构和能量.
- 计算的路径与标记实验中确定的实验结果进行了比较.
- 理论分析被用来解释X射线晶体结构数据的taxadiene合成.
主要成果:
- 建立了一个完整的,从能源上可行的途径,从格兰二酸到纳税.
- 计算的途径与实验标记数据一致,但表明了碳酸介质的新型构造.
- 与之前的机械模型相比,在键形成同步性上发现了微妙的差异.
- 在基于理论结果的基础上,在纳税二烯合成中提出了2-基拉尼尔基拉尼尔二酸盐的非生产性结合方向.
结论:
- 这项研究提供了一个详细的,理论上验证的纳税生物合成机制.
- 这些发现为在烯循环过程中碳化中间体的结构灵活性提供了新的见解.
- 拟议的非生产性结合模式挑战了对税二烯合成酶基质相互作用的现有解释.
相关概念视频
Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.
[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.
Thermal Electrocyclic Reactions: Stereochemistry
The stereochemistry of electrocyclic reactions is strongly influenced by the orbital symmetry of the polyene HOMO. Under thermal conditions, the reaction proceeds via the ground-state HOMO.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
Thermal and Photochemical Electrocyclic Reactions: Overview
Electrocyclic reactions are reversible reactions. They involve an intramolecular cyclization or ring-opening of a conjugated polyene. Shown below are two examples of electrocyclic reactions. In the first reaction, the formation of the cyclic product is favored. In contrast, in the second reaction, ring-opening is favored due to the high ring strain associated with cyclobutene formation.
Cationic Chain-Growth Polymerization: Mechanism
The cationic polymerization mechanism consists of three steps: initiation, propagation, and termination. In the initiation step of the polymerization process, the π bond of a monomer gets protonated by the Lewis acid catalyst, which is formed from boron trifluoride and water. The protonation of the π bond generates a carbocation stabilized by the electron‐donating group. In the propagation step, the π bond of the second monomer acts as a nucleophile and attacks the generated carbocation,...
Photochemical Electrocyclic Reactions: Stereochemistry
The absorption of UV–visible light by conjugated systems causes the promotion of an electron from the ground state to the excited state. Consequently, photochemical electrocyclic reactions proceed via the excited-state HOMO rather than the ground-state HOMO. Since the ground- and excited-state HOMOs have different symmetries, the stereochemical outcome of electrocyclic reactions depends on the mode of activation; i.e., thermal or photochemical.
Selection Rules: Photochemical Activation
Selection Rules: Photochemical Activation

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