Physiologically Active Natural Products

生理活性天然产物

• 批准号: 7211482
• 负责人: DOUGLASS F. TABER
• 金额: $ 29.67万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7211482
• 关键词: Alkaloids; Antifungal Agents; Biological Factors; Complex; Computing Methodologies; Delphinium; Development; Diterpenes; Exercise; Facility Construction Funding Category; Investigation; Methods; Molecular; Morphine; N-deacetyllappaconitine; Natural Product Drug; Perception; Pharmaceutical Preparations; Pharmacologic Substance; Preparation; Purpose; Research; Route; Sodium Channel; Tetrodotoxin; carbene; improved; interest; programs; receptor binding; sordaricin

DESCRIPTION (provided by applicant): As the computational methods used in pharmaceutical development improve, receptor binding analysis has led to many potential new drug candidates that are polycyclic. Such leads are often not pursued, however, because of the perception that even if the compound were active, an enantiomerically pure polycyclic candidate would be too expensive to manufacture. An investigation of a new method for the construction of carbocyclic rings, intramolecular alkylidene C-H insertion, is proposed. One could take nearly any complex cyclic molecule and do a retrosynthetic disconnection in such a way as to generate an alkylidene carbene precursor. Tetrodotoxin, N-deacetyllappaconitine and sordaricin have been selected as targets because of their structural interest and their pharmacological significance. In the course of these investigations, new molecular reactivity will be developed that will substantially shorten current routes to polycyclic natural products and drug candidates.

描述（由申请人提供）：随着药物开发中使用的计算方法的改进，受体结合分析已经产生了许多潜在的多环新候选药物。然而，此类先导化合物通常不被追寻，因为人们认为即使该化合物具有活性，对映体纯的多环候选物的制造成本也太昂贵。提出了一种构建碳环的新方法——分子内亚烷基C-H插入的研究。人们可以采用几乎任何复杂的环状分子，并以生成亚烷基卡宾前体的方式进行逆合成断开。河鲀毒素、N-脱乙酰高乌甲碱和sordaricin因其结构意义和药理学意义而被选为靶标。在这些研究过程中，将开发新的分子反应性，这将大大缩短目前多环天然产物和候选药物的路线。