An Environmentally Benign Method for the Synthesis of C-aryl Glycosides

一种环境友好的 C-芳基糖苷合成方法

• 批准号: 7287967
• 负责人: Thomas Gerard Minehan
• 金额: $ 9.65万
• 依托单位: CALIFORNIA STATE UNIVERSITY NORTHRIDGE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7287967
• 关键词: Acids; Adopted; Antifungal Agents; Antifungal Antibiotics; Benign; Biological; Biological Factors; C-glycoside; Carbohydrates; Carbon; Chemical Industry; Chemicals; Class; Communicable Diseases; Complex; Condition; Corrosives; Development; Ecosystem; Evaluation; Facility Construction Funding Category; Family; Future; Glycosides; Goals; Health; Human; Isomerism; Metals; Methodological Studies; Methodology; Methods; Mind; Modeling; NMR Spectroscopy; Object Attachment; Pharmacologic Substance; Preparation; Procedures; Process; Property; Protocols documentation; Purpose; Reaction; Reagent; Research; Scientist; Solvents; Staging; Students; Temperature; Testing; Transition Elements; Variant; Zinc; analog; antineoplastic antibiotics; catalyst; desire; experience; fighting; improved; liquid chromatography mass spectrometry; novel; pluramycin; programs; research study; stereochemistry; tool; toxic metal

DESCRIPTION (provided by applicant): The long-term objective of this project is to develop an environmentally friendly method for the preparation of 2-deoxy-C-aryl glycosides, a family of natural products which demonstrate important biological properties such as antitumor, antibiotic and antifungal activities. Previous approaches to the synthesis of this class of compounds have involved the use of corrosive Lewis acids or toxic metals for the preparation of the carbon-carbon linkage between carbohydrate and aromatic moieties. Although we have previously shown that benign organoindium reagents may be employed in fashioning the glycosidic carbon-carbon bond efficiently, we wish to explore a new method that will allow the construction of this bond with the stereochemical configuration found in the natural products. With this goal in mind, we will investigate the preparation and reactivity of benign glycosyl zinc reagents as key intermediates in the synthesis of C-aryl glycosides. It is anticipated that temperature will be a key factor in determining the orientation of the carbon-zinc bond, which ultimately will determine the stereochemistry of the glycosidic carbon-carbon bond. Optimal conditions for the transition-metal catalyzed cross-coupling reaction between the glycosyl zinc reagent and aryl halides or triflates for the formation of the C-glycosides will also be explored. Finally, to assess the broad utility of this method, the preparation of the glycosidic core of the angucycline natural product Sch 47555 will be undertaken, and the mildness of the reaction conditions will be gauged by attempting a late-stage joining of fully functionalized carbohydrate and aromatic units bearing a sensitive O-glycosidic linkage. Because of the pronounced biological activities of the C-aryl glycosides, it is likely that even structural variants and simplified analogs of these natural products will have intriguing properties; as a result, a further aim of our synthetic efforts is to produce sufficient quantities of these substances for pharmacological evaluation. If successful, this research will provide scientists with an additional tool for the assembly of medicinally relevant compounds to fight sickness and infectious disease. Furthermore, if such environmentally benign protocols are widely adopted in the chemical industries, the negative impacts of large-scale chemical processes on fragile ecosystems and the biosphere will be diminished, which in the long term will result in improved human health.

描述（由申请人提供）：该项目的长期目标是开发一种环保方法，以制备2-脱氧-C-芳基糖苷，这是一种天然产物家族，表现出重要的生物学特性，例如抗肿瘤，抗生素和抗真菌活性。以前的合成这类化合物的方法涉及使用腐蚀性路易斯酸或有毒金属来制备碳水化合物和芳香族部分之间的碳碳连锁。尽管我们以前已经表明，良性有机体试剂可以有效地塑造糖苷碳 - 碳键，但我们希望探索一种新方法，该方法将允许使用天然产物中的立体化学构型构建这种键。考虑到这一目标，我们将研究良性糖基锌试剂作为C-酰亚他化糖苷合成的关键中间体的制备和反应性。预计温度将是确定碳 - 锌键取向的关键因素，最终将确定糖苷碳碳键的立体化学。还将探索糖基锌试剂和芳基卤化物或三片形成C-糖苷的过渡金属催化的交叉偶联反应的最佳条件。最后，为了评估这种方法的广泛效用，将进行angucycline天然产物SCH 47555的糖苷核心的制备，并且将通过尝试通过官能化官能化的碳水化合物和芳族的单位来估算反应条件的温和性，并具有敏感的O-GlyCosidic链接。由于C-芳基糖苷的显着生物学活性，即使是结构上的变体和这些天然产物的简化类似物也可能具有有趣的特性。结果，我们的合成工作的进一步目的是生产足够数量的这些物质进行药理学评估。如果成功，这项研究将为科学家提供额外的工具，用于组装与疾病和传染病的药物相关化合物。此外，如果在化学工业中广泛采用这种环境良性方案，大型化学过程对脆弱生态系统和生物圈的负面影响将减少，从长远来看，这将改善人类健康。