Practical Synthesis of Chiral Building Blocks for Molecular Library of Organic Compounds

有机化合物分子库手性构件的实际合成

基本信息

批准号：
13650919
负责人：
HARADA Toshiro
金额：
$ 2.24万
依托单位：
Kyoto Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13650919/
关键词：
Asymmetric Synthesis Diol Chiral Building BLock Asymmetric Desymmetrization

项目摘要

Enantiomerically enriched mono-protected derivatives of 2-substitued 1,3-propanediols are useful chiral building blocks which have been frequently employed in natural product synthesis. One of the moststraightforward methods for their preparation involves asymmetric desymmetrization of parent prochiral propanediols or their derivatives and enzyme-mediated transesterification or hydrolysis has been used for this purpose. A few reports have been appeared on nonenzymatic approach which could be of wide generality allowing to prepare a tailor-made chiral building blocks appropriate for the molecular library of organic compounds. Nonenzymatic desymmetrization of 2-substitutcd 1,3-propanediols leading to the enantiomerically enriched 3-benzyloxy-1-propanols was achieved by using from N-tosyl-(L)-naphthylalanine-derived oxazaborolidinone-mediated enantioselective ring-cleavage reaction of the dioxane acetal derivatives as a key reaction. The method was found to be highly effective for propanediols bearing a relatively bulky substituent at the 2 position. Further survey of reaction conditions to reduce the amount of the oxazaborolidinone revealed that the use of diethyl ether as an additive is effective. In the presence of the additive, highly selective ring-cleavage reaction was realized even when 0.5 equiv of oxamborolidinone was employed. In addition to this, the use of dimethylsilyl ketene S,O-acetal as a nucleophile is also found to be effective for the catalytic enantioselective ring-cleavage reaction.

2-取代1,3-丙二醇的对映体富集单保护衍生物是有用的手性结构单元，经常用于天然产物合成。其最直接的制备方法之一涉及母体前手性丙二醇或其衍生物的不对称去对称化，并且酶介导的酯交换或水解已用于此目的。已经出现了一些关于非酶方法的报告，该方法具有广泛的通用性，可以制备适合有机化合物分子库的定制手性构件。通过使用 N-甲苯磺酰基-(L)-萘基丙氨酸衍生的恶唑硼烷酮介导的二恶烷的对映选择性环裂解反应，实现了 2-取代的 1,3-丙二醇的非酶去对称化，产生对映体富集的 3-苄氧基-1-丙醇缩醛衍生物作为关键反应。发现该方法对于在 2 位带有相对较大取代基的丙二醇非常有效。对减少恶唑硼烷酮用量的反应条件的进一步研究表明，使用二乙醚作为添加剂是有效的。在添加剂存在下，即使使用0.5当量的氧硼烷酮，也能实现高选择性的开环反应。除此之外，还发现使用二甲基甲硅烷基烯酮S,O-缩醛作为亲核试剂对于催化对映选择性开环反应是有效的。