Dearomative Functionalization with Arenophiles

亲仁体的脱芳香功能化

• 批准号: 10794085
• 负责人: David Sarlah
• 金额: $ 17.59万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10794085
• 关键词: Address; Agrochemicals; Alkenes; Antibiotics; Area; Aromatic Compounds; Biological; Catalysis; Chemicals; Chemistry; Complex; Drug Kinetics; Funding; Goals; Left; Natural Products; Pharmaceutical Chemistry; Pharmacologic Substance; Preparation; Prodrugs; Property; Reaction; Route; Series; Transition Elements; Work; analog; anti-cancer; bioactive natural products; design; improved; instrument; nucleophilic substitution; parent grant; small molecule

PROJECT SUMMARY The objective of the work of the parent grant is to provide new chemical transformations and strategies that will selectively introduce functionality and, consequently, greatly expand the dearomative chemical toolbox. Small, heteroatom-containing complex molecules are common motifs of biological (as well as pharmaceutical and agrochemical) relevance and are highly desired in medicinal chemistry, but they are also often difficult to access. Selective transformations of aromatic compounds could provide a more direct route to such desirable targets; however, the many challenges associated with dearomative functionalization have left these types of reactions widely underdeveloped. We strive to address this need by bridging the gap between dearomatization and alkene chemistry. Fundamentally, the goal of this proposal is to access desirable structural motifs from simple aromatic compounds by developing dearomative functionalizations using small molecules – arenophiles – that enable reactions of isolated alkenes in an arene substrate. Additionally, arenophiles, in combination with transition metal catalysis, provide uniquely reactive substrates for nucleophilic substitution reactions, and could enable the rapid synthesis of a diverse range of aminofunctionalized alicyclic compounds. We have prepared a series of potent anticancer natural products and antibiotics and are currently preparing analogues for SAR studies as well as designing prodrugs with improved pharmacokinetics properties. The instrument, UHPLC-MS, to be purchased by funds from this Supplement will allow us for analysis of these highly polar compounds and will greatly facilitate these studies.

项目摘要 父母赠款工作的目的是提供新的化学转化和策略 这将有选择地介绍功能，因此大大扩展了亲爱的化学工具箱。 含杂种的小分子是生物学的常见基序（以及 药物和农业化学）相关性，在医学化学中是高度期望的，但它们也是 通常很难访问。芳香化合物的选择性转换可以提供更直接的途径 这样理想的目标；但是，剩下的与临界功能相关的许多挑战已经剩下 这些类型的反应广泛发达。我们努力通过弥合之间的差距来满足这种需求 亲爱的，烯烃化学。从根本上讲，该提议的目的是访问理想的结构 通过使用小分子开发出亲爱的功能化的简单芳香化合物的基序 - 闪光灯 - 能够在芳烃底物中分离的烷烃反应。此外，闪光灯，在 与过渡金属催化结合使用，为核类抗性取代提供了独特的反应性底物 反应，并且可以使氨基官能化的型环化合物的分化范围迅速合成。 我们已经准备了一系列潜在的抗癌天然产品和抗生素，目前正在准备 用于SAR研究的类似物以及具有改进的药代动力学特性的前药。这 仪器，UHPLC-MS，将从该补充剂中购买的资金购买将使我们对这些高度分析 极性化合物，将极大地支持这些研究。