Use of Silyl Glyoxylates in Tandem Vinylation/Brook Rearrangement/Adol Reactions

乙醛酸甲硅烷基酯在串联乙烯基化/布鲁克重排/Adol 反应中的用途

• 批准号: 7321743
• 负责人: Rebecca Ann Duenes Cuellar
• 金额: $ 2.4万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-11 至 2008-05-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7321743
• 关键词: 3-hydroxybutanal; Acids; Alcohols; Aldehydes; Antifungal Agents; Biological Factors; Complex; DNA Sequence Rearrangement; Esters; Evolution; Facility Construction Funding Category; Generations; Glyoxylates; Goals; Hydrogenation; Hydroxyl Radical; In Situ; Iridium; Ligands; Medicine; Menthol; Methodology; Numbers; Object Attachment; Organic Synthesis; Pharmacologic Substance; Reaction; Research; Rhodium; Scheme; Sparteine; Therapeutic; Time; carbonyl compound; design; functional group; glyoxylate; phenylalaninol; stereochemistry; valinol

DESCRIPTION (provided by applicant): Tandem reactions and multicomponent couplings have long been a desirable goal for organic synthesis, as they quickly and efficiently fashion complex molecules from simpler starting materials. The long term goal of this project is to devise diastereo- and enantioselective reactions that can be used in the synthetic design of natural products and pharmaceutically relevant building blocks. This proposal focuses on the generation of a,(3-dihydroxy, v-chiral carbonyl compounds from the domino reaction of silylglyoxylates, vinyl Grignard, and aldehydes. Specifically the strategy presented is to: i) examine induction of enantioselectivity by making a chiral silylglyoxylate via the ester functionality such as usage of 8-phenyl-menthol, valinol, and phenylalaninol; ii) examine induction of enantioselectivity via chiral Grignard ligands such as (-)-sparteine, trans- 1,2-diaminocyclohexane, and /V,A/-dimethylpseudoephedrine. iii) assess the potential for addition to prochiral aldehydes (e.g. tiglic aldehyde) followed by enantioselective hydroxyl-directed hydrogenation using cationic rhodium or iridium species; iv) utilize the aforementioned methodology in the most concise synthesis to date of the antifungal, phytotoxic natural product alternaric acid. A wide number of therapeutics are either natural products themselves or derived from natural products, most often with specific orientations (stereochemistry) of bonds and functional groups. This research aims to access portions of these would-be Pharmaceuticals in a succinct manner via assembly of multiple segments at one time, complete with stereochemical integrity. Through rapid construction of these components, potential medicines can be synthesized more quickly for further study.

描述（由申请人提供）：串联反应和多组分偶联长期以来一直是有机合成的理想目标，因为它们从较简单的起始材料快速有效地形成复杂的分子。该项目的长期目标是设计非对映体和对映体选择性反应，可用于天然产物和药学相关构件的合成设计。本论文主要研究了由乙醛酸硅烷酯、乙烯基格氏试剂和醛的多米诺反应生成α，β-二羟基，V-手性羰基化合物。具体来说，提出的战略是： i）通过经由酯官能团制备手性甲硅烷基乙醛酸酯，例如使用8-苯基-薄荷醇、缬氨醇和苯丙氨醇，检查对映选择性的诱导; ii）检查通过手性格氏配体如（-）-鹰爪豆碱、反式-1，2-二氨基环己烷和N，N-二甲基伪麻黄碱诱导对映选择性。 iii）评估加成到前手性醛（例如惕各醛）上，然后使用阳离子铑或铱物质进行对映选择性羟基定向氢化的潜力; iv）在迄今为止抗真菌、植物毒性天然产物交链孢酸的最简洁的合成中利用上述方法。 许多治疗剂本身是天然产物或衍生自天然产物，最常见的是具有键和官能团的特定取向（立体化学）。这项研究旨在通过一次组装多个片段，以简洁的方式获得这些潜在药物的一部分，并完成立体化学完整性。通过快速构建这些组分，可以更快地合成潜在的药物以供进一步研究。