Organic Chemistry: Multistep Synt#hsis, New Synthetic Methodology, Exploratory Chemistry

有机化学：多步合成

• 批准号: 8721823
• 负责人: Elias Corey
• 金额: $ 175.01万
• 依托单位: Harvard University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-01-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8721823&HistoricalAwards=false
• 关键词: Organic; Chemistry; Multistep; Synt#hsis; New

This program, supported by the Organic and Macromolecular section covers a broad area of synthetic organic chemistry.The synthesis by multistep processes of several naturally occurring and biologically active complex organic molecules is under study. Most of the molecules under study are of unusual interest because of their biological activities. Some may be of value in the development of new human therapeutic agents. Hand in hand with the objective of achieving simple and effective syntheses of specific target structures is the development of new general synthetic organic reactions and methods and demonstrating their usefulness in the chosen multistep synthetic problems. The discovery of such methods amplifies the power of synthesis and extends its range of application to ever more formidable structures. In the course of this effort, a deeper appreciation of various fields of chemistry, e.g. organometallic chemistry and chemical theory, can be gained. In the area of multistep synthesis the following specific projects are being carried out: (1) synthesis of chiral C15 gingkolides; bilobalide and analogs; (2) synthesis of chiral C20 gingkolides and analogs; (3) synthesis of kadsuranone and other antagonists of platelet activating factor (PAF ac ether, or simply PAF); (4) synthesis of preclavulone-A and more complex marine eicosanoids derived therefrom; (5) synthesis of pseudopterosin; (6) synthesis of glycinoeclepin; (7) synthesis of venustatriol; (8) synthesis of biotin; (9) synthesis of protosterol; (10) synthesis of tricyclohexaprenol. In the areas of new synthetic methodology a number of projects are directed at the important problem of enantioselectivity in synthesis including the following: (1) further studies to extend and broaden the important discovery of catalytic, enantioselective reductions by borane; (2) enantioselective 1,2 -addition of carbon to aldehydes and ketones; (3) enantioselective conjugate addition of cuprates and other organometallic reagents to enones; (4) catalytic enantioselective cyclopropanation; (5) new chiral controller groups and reagents. Finally, a number of new methods will be studied which ultimately will lead to new and practical methods of oxidation, C-C bond formations, and ring formation reactions.

该计划由有机和高分子部分支持，涵盖了合成有机化学的广泛领域。通过多步过程合成几个天然存在的具有生物活性的复杂有机分子正在研究中。大多数正在研究的分子因其生物活性而引起人们的极大兴趣。其中一些可能在开发新的人类治疗剂方面有价值。与实现简单有效地合成特定目标结构的目标齐头并进的是开发新的一般合成有机反应和方法，并展示它们在选定的多步骤合成问题中的有效性。这种方法的发现扩大了合成的力量，并将其应用范围扩大到更强大的结构。在这一过程中，可以对化学的各个领域，如有机金属化学和化学理论，有更深的了解。在多步合成方面，正在进行以下具体项目：(1)手性C15银杏内酯、白果内酯及其类似物的合成；(2)手性C20银杏内酯及其类似物的合成；(3)海风藤酮和其他血小板激活因子拮抗剂(PAF-Ac-ether，简称PAF)的合成；(4)前克拉维酮-A及其衍生的更复杂的海洋二十烷类化合物的合成；(5)拟蝶形素的合成；(6)甘氨酸乙酯的合成；(7)文宁他汀醇的合成；(8)生物素的合成；(9)原甾醇的合成；(10)三环已丙肾上醇的合成。在新的合成方法学领域，许多项目是针对合成中的对映体选择性这一重要问题进行的，包括：(1)进一步研究以推广和扩大硼烷催化、对映体选择性还原的重要发现；(2)醛和酮的1，2-碳对映体选择性加成反应；(3)铜酸盐和其他有机金属试剂与烯酮的不对称共轭加成反应；(4)催化不对称环丙烷化反应；(5)新型手性控制基团和试剂。最后，将研究一些新的方法，这些方法最终将导致新的和实用的氧化、C-C键形成和环形成反应的方法。