总合成和确定frondosin B的绝对配置
M Inoue1, M W Carson, A J Frontier
1Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10021, USA.
Journal of the American Chemical Society
|July 18, 2001
概括
开发了两种新合成的frondosin B,一种介素-8受体对抗剂. 这些路径确定了frondosin B的绝对配置,确认了二次甲基中心的R配置.
科学领域:
- 有机合成 有机合成
- 药用化学 医学化学
背景情况:
- 佛朗多B是一种互乐金-8受体对抗剂.
- 开发高效的合成路径对于药物发现和开发至关重要.
研究的目的:
- 为了实现 (+/-) -frondosin B. 的简洁的总合成.
- 为了确定frondosin B的绝对配置.
主要方法:
- 经典的Friedel-Crafts反应形成一个七分环.
- 电离子循环和迪尔斯-阿尔德反应用于构建碳环环.
- 选择性合成以建立绝对的配置.
主要成果:
- 从5 - 甲西酸成功地建立了两条截然不同的合成路径到frondosin B.
- 迪尔斯-阿尔德的方法有效控制了双重债券的定位.
- 第三个enantioselective合成证实了二次甲基中心的R配置.
结论:
- 在frondosin B中二次甲基中心的绝对配置是R.
- 这些合成为frondosin B核心结构的构建提供了宝贵的见解.
相关概念视频
Fischer Projections
Learning to draw Fischer projections of molecules and understanding their relevance plays a crucial role in the visual depiction of organic molecules. A Fischer projection is a two-dimensional projection on a planar surface to simplify the three-dimensional wedge–dash representation of molecules. This is especially helpful in the case of molecules with multiple chiral centers that can be difficult to draw. Here, all the bonds of interest are represented as horizontal or vertical lines. While...
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.
Frost Circles for Different Conjugated Systems
The inscribed polygon method is consistent with Hückel’s 4n + 2 rule and helps to learn whether the given cyclic compound is aromatic or not. The compound is stable and aromatic if every bonding molecular orbital (MO) is completely filled with a pair of electrons. However, if the non-bonding or antibonding orbitals are filled with electrons, the compound is unstable and not aromatic. Consider the Frost circle diagrams for cycloalkenes containing 4 to 8 carbons.
Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations
Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
Antifungal Agents
Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...


