(-) - 和ent-(+) -vindoline以及相关的类化合物的总合成
Hayato Ishikawa1, Gregory I Elliott, Juraj Velcicky
1Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|August 10, 2006
概括
使用一种新的双重循环加法,实现了11个步骤的vindoline enantiomers合成. 这种高效的方法快速构建五环芯,设置立体中心,并在一步中引入关键功能.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 自然产品的合成自然产品的合成
背景情况:
- 芬多林是重要的药品的关键化物前体.
- 对于药物开发来说,高效的合成路径到vindoline及其类似物至关重要.
- 以前的合成通常涉及许多步骤和有限的立体化学控制.
研究的目的:
- 开发一个简洁而高效的vindoline及其反体的总合成.
- 为构建复杂的五循环系统建立一种新的双重循环加法策略.
- 通过合成相关的自然产品来证明开发的方法的多功能性.
主要方法:
- 一个11个步骤的总合成利用一个1,3,4-oxadiazole的双重分子内 [4 + 2]/[3 + 2]循环添加.
- 在五环核中形成六个立体中心的立体选择性形成.
- 应用开发的方法来合成各种vindoline类似物和相关的天然产品.
主要成果:
- 在11个步骤中成功合成了 (-) - 和 ent-(+) -vindoline.
- 在单个关键步骤中形成三个环和四个C-C键,建立五环核心.
- 合成了米诺,芬多和相关化合物的两个反体,展示了该方法的范围.
结论:
- 开发的双重循环添加级联为vindoline及其类似物提供了高效和立体选择性路线.
- 这一策略显著缩短了合成途径到复杂的醇类化合物.
- 该方法提供了一个强大的工具,用于获取各种天然产品和潜在的候选药物.
更多相关视频
相关概念视频
01:26Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.
01:16Cycloaddition Reactions: Overview
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
01:27Vicinal Diols via Reductive Coupling of Aldehydes or Ketones: Pinacol Coupling Overview
Wilhelm Rudolph Fittig discovered the pinacol coupling reaction in 1859. It is a radical dimerization reaction and involves the reductive coupling of aldehydes or ketones in the presence of hydrocarbon solvent to yield vicinal diols.
01:29Drugs Affecting Neurotransmitter Synthesis
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase, which converts...
01:20Opioid Analgesics: Morphine and Other Natural Cogeners
Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...