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Innovational Asymmetric Catalysis縲廾ptimization and New Development

创新不对称催化优化与新发展

基本信息

批准号：
15002003
负责人：
SHIBASAKI Masakatsu
金额：
$ 290.37万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Specially Promoted Research
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2007
项目状态：
已结题

项目摘要

We developed a practical catalytic asymmetric Strecker reaction of ketimines using glucose-derived ligands. Directing toward industrial application, we improved the catalyst turnover efficiency in 100 times using an achiral protic additive. Inexpensive HCN can be used as a cyanide source in this reaction. This is the most general and practical catalytic asymmetric Strecker reacton of ketimines to date. In addition, we developed a new efficient synthetic route of the chiral ligand, which allowed us to synthesize both enantiomers of the ligand. The related catalyst can promote highly enantioselective ring-opening reaction of meso-aziridines with TMSN_3. This reaction was a platform for the synthesis of anti-influenza drug, Tamiflu.Et_2Zn/linked-BINOL catalyst promoted both anti-and syn-selective direct Mannich reaction of hydroxy ketones. Both diastereomers of the products can be synthesized depening on the reaction conditions with up to 99% ee. The catalyst loading was reduced to 0.01 mol %, which is the far lowest catalyst loading in asymmetric Mannich reaction. The same catalyst also promoted aldol reaction and Michael reaction using the minimum amount of the catalyst.A chiral rare earth metal-amide catalyst was recently developed, and found to be effective in asymmetric animation reactions. This finding led to develop a practical synthetic route of ranirestat, an anti-diabetic agent.

我们利用葡萄糖衍生的配体开发了一种实用的酮亚胺的不对称Strecker反应。针对工业应用，我们使用了一种无手性质子添加剂，使催化剂的循环效率提高了100倍。在该反应中，可以用廉价的HCN作为氰化源。这是迄今为止最普遍和最实用的不对称催化Strecker反应。此外，我们开发了一种新的高效的手性配体的合成路线，使我们能够合成这两种配体的对映体。该催化剂能促进中氮杂环丙烷与TSMN_3的高对映选择性开环反应，为合成抗流感药物达菲提供了平台。Et_2ZN/Linked-BINOL催化剂促进了羟基酮的反选择性和合成选择性的直接Mannich反应。根据反应条件的不同，产物的两种非对映异构体均可合成，ee可达99%。催化剂负载量降至0.01mol%，是不对称Mannich反应中负载量最低的催化剂。同样的催化剂还可以用最少的催化剂促进Aldol反应和Michael反应。最近开发了一种手性稀土金属酰胺催化剂，并发现它在不对称动画反应中是有效的。这一发现导致开发了一种实用的抗糖尿病药物雷尼司他的合成路线。