タイランスタチンAの総合合成
K C Nicolaou1, Derek Rhoades, Manjunath Lamani
1Department of Chemistry, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
Journal of the American Chemical Society
|June 9, 2016
まとめ
研究者は新しいバイオミメティック反応を用いて,スプリセソーム阻害剤であるタイランスタチンAの全合成を達成した. この方法は,この生物活性分子のアナログを作成するための機能化されたテトラヒドロピランにアクセスできます.
科学分野:
- 有機化学
- 薬剤化学
- 化学生物学
背景:
- タイランスタチンAは有意な生物学的活性を持つ強力なスプリセソーム阻害剤です.
- 複雑な天然製品への効率的な合成経路の開発は 薬剤発見とアナログ開発に不可欠です
研究 の 目的:
- タイランスタチンAの完全な合成を達成するために
- 機能化されたテトラヒドロピランへのアクセスのための新しい合成戦略を開発する.
- タイランスタチンAの合成を可能にする.
主な方法:
- 9段階のタイランスタチンAの総合合成が開発された.
- 重要なステップは,バイオミメティックな非対称な分子内オクサ-マイケルの反応/水素化配列でした.
- このシーケンスにより,テトラヒドロピラン基板のダイアステレオダイバーゲント合成が可能になった.
主要な成果:
- タイランスタチンAの全合成が成功しました.
- 開発された方法は,高度に機能化されたテトラヒドロピランへの効率的なアクセスを提供します.
- 合成戦略は,タイランスタチンAの類似品の作成に適しています.
結論:
- タイランスタチンAの完全な合成は,革新的な効率的な経路で達成されました.
- バイオミメティック反応配列は,関連する生物活性分子を合成するための汎用的なプラットフォームを提供します.
- この研究は,タイランスタチンAの治療の可能性をさらに探求することを容易にする.
関連する概念動画
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
1.7K
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
1.7K
00:51Synthesis and Functions of Calcitonin
5.2K
Calcitonin, a vital polypeptide hormone, regulates calcium levels within body fluids. It is released by the parafollicular cells, also known as C cells, situated in the follicular epithelium of the thyroid gland. Calcitonin responds to fluctuations in blood calcium levels and the influence of gastrointestinal hormones like gastrin and cholecystokinin.
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
5.2K
01:18Functions of Thyroid Hormones
6.4K
The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
6.4K
01:20Synthesis and Regulation of Thyroid Hormones
8.8K
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
8.8K
01:29Biosynthesis of Lipids
836
Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...
836
01:30Production of Pharmaceuticals
4
Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under...
4