一个15步合成 (+) - 醇
Kangway V Chuang1, Chen Xu1, Sarah E Reisman2
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
概括
一种复杂的二类药物 (+) - 瑞诺多尔在15个步骤中合成. 这种合成受体调节器的高效方法利用关键反应来快速构建碳框架和安装氧气.
科学领域:
- 有机化学
- 分子生物学
- 生物物理
背景情况:
- (+) - 瑞诺丁和 (+) - 瑞诺丁是复杂的二类化合物,通过瑞诺丁受体调节细胞内离子释放.
- 瑞诺丁受体对于肌肉激发-收缩合和突触传输至关重要.
- 这些二类的结构变化可能会影响它们对氨酸受体异型的结合亲和力和选择性.
研究的目的:
- 开发一个简洁而高效的 (+) - 醇的化学合成.
- 探索战略性C-O键结构以简化多化合成.
主要方法:
- 从 (S) - pulegone 中合成 (+) - ryanodol 的 15 个步骤.
- 使用Pauson-Khand反应进行快速碳框架组装.
- 采用SeO2介导的氧化方法,同时安装三个氧原子.
主要成果:
- 在相对较少的步骤中成功合成 (+) - 醇.
- 在这种合成中证明了Pauson-Khand反应和SeO2中介氧化的效率.
- 强调了战略性C-O债券形成的重要性.
结论:
- 已经实现了 (+) - 醇的短时间和高效合成.
- 这种合成途径最大限度地减少了保护组和氧化还原调整的需要.
- 该策略适用于合成其他多化.
相关概念视频
Synthesis and Decomposition Reactions
31.3K
Synthesis and decomposition are two types of redox reactions. Synthesis means to make something, whereas decomposition means to break something. The reactions are accompanied by chemical and energy changes.
31.3K
Preparation of Amides
3.4K
Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
3.4K
Preparation of Nitriles
1.9K
One of the common methods to prepare nitriles is the dehydration of amides. This method requires strong dehydrating agents like phosphorous pentoxide or boiling acetic anhydride for converting amides to nitriles. Another reagent namely, thionyl chloride also accomplishes the dehydration of amides, where amide acts as a nucleophile. The first step of the mechanism involves the nucleophilic attack by the amide on the thionyl chloride to form an intermediate. In the next step, the electron pairs...
1.9K
Acid-Catalyzed Aldol Addition Reaction
2.3K
The aldol reaction of a ketone under acidic conditions successfully forms an unsaturated carbonyl as the final product instead of an aldol. The acid-catalyzed aldol reaction is depicted in Figure 1.
2.3K
Conjugate Addition (1,4-Addition) vs Direct Addition (1,2-Addition)
3.4K
α,β-Unsaturated carbonyl compounds with two electrophilic sites, the carbonyl carbon, and the β carbon, are susceptible to nucleophilic attack via two modes: conjugate or 1,4-addition and direct or 1,2-addition.
Conjugate addition results in a thermodynamically stable product. The reaction retains the stronger C=O bond at the expense of the weaker C=C π bond. The process is slow as the β carbon is less electrophilic than the carbonyl carbon.
Direct addition products are...
Conjugate addition results in a thermodynamically stable product. The reaction retains the stronger C=O bond at the expense of the weaker C=C π bond. The process is slow as the β carbon is less electrophilic than the carbonyl carbon.
Direct addition products are...
3.4K
Leveling Effect
1.6K
In acid-base chemistry, the leveling effect refers to the limitation imposed by the solvent on the strength of acids and bases in solution. When a base stronger than the solvent's conjugate base is used, it deprotonates the solvent until the base is entirely consumed, making it ineffective against weaker acids. Conversely, an acid stronger than the solvent's conjugate acid protonates the solvent until the acid is depleted, rendering it ineffective against weaker bases. Essentially, the...
1.6K


