SYNTHESIS OF A-HYDROXYCARBONYL COMPOUNDS

A-羟基羰基化合物的合成

• 批准号: 3284376
• 负责人: FRANKLIN A DAVIS
• 金额: $ 9.25万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-06-01 至 1988-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3284376
• 关键词: acetylation; aziridines; beta lactam antibiotic; carbonyl compound; chelating agents; chemical structure function; drug design /synthesis /production; drug screening /evaluation; enolate; ketones; lactones; metal complex; oxidation; oxygen transport

The aim of the proposed work is to develop methodology for the direct oxidation and asymmetric oxidation of enolates to Alpha-hydroxycarbonyl compounds (R2C(OH)C(O)-Z). Compounds having the Alpha-hydroxycarbonyl structural unit are ubiquitous in nature and responsible, for the biological activity of many compounds having this subunit. These goals will be achieved by exploring the oxidation of enolates (enol silyl ethers, enamines, metaloenamines) using 2-sulfonyloxaziridines, aprotic and neutral oxidizing agents. Oxidation of chiral enolates using these reagents is anticipated to give optically active Alpha-hydroxycarbonyl compounds in high optical purity. Studies of enolate oxidations with chiral 2-sulfonyl- and 2-sulfamyloxaziridines will provide insights into the origins of asymmetric induction and new information on electrophile-enolate trajectories. Metal assisted asymmetric oxidations using 2-sulfamyloxaziridines having metal chelating functional groups are anticipated to give Alpha-hydroxycarbonyl compounds in high enantiotopic purity. This methodology will be applied to the chiral synthesis of (-)-Eucomol and (+)-demethoxydaunomycinone; the latter compound is a potent anti-tumor agent. The feasibility of direct enolate and asymmetric enolate oxidation as a viable synthetic route to Alpha-hydroxycarbonyl compounds has been demonstrated by preliminary studies.

拟议工作的目的是为直接的 烯醇化物向α-羟基羰基的氧化和不对称氧化 化合物（R2 C（OH）C（O）-Z）。 具有α-羟基羰基的化合物 结构单位在自然界中普遍存在， 具有这种亚基的许多化合物的生物活性。 这些目标 将通过探索烯醇化物（烯醇甲硅烷基醚， 烯胺，金属烯胺），使用2-磺酰氧氮杂环丙烷，非质子和中性 氧化剂 使用这些试剂的手性烯醇化物的氧化是 预期在2000年12月至2005年12月期间， 光学纯度高。 手性2-磺酰基-β-环糊精氧化烯醇化物的研究 和2-磺酰氧氮杂环丙烷将提供深入了解的起源， 亲电烯醇化物不对称诱导及新信息 轨迹 金属辅助的不对称氧化， 2-具有金属螯合官能团的磺酰氧氮杂环丙烷， 预期得到高对映异构体的α-羟基羰基化合物 纯度 该方法将被应用于手性合成 （-）-Eucomol和（+）-去甲氧基柔红霉素酮;后一种化合物是有效的 抗肿瘤剂。 研究了直接烯醇化物和不对称烯醇化物氧化作为一种 α-羟基羰基化合物的可行合成路线已经 初步研究表明。