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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.

对映体富集的2-取代1,3-丙二醇单保护衍生物是一种有用的手性结构单元，在天然产物合成中被广泛应用。制备它们的最直接的方法之一是母体前手性丙二醇或其衍生物的不对称去对称化，并为此目的使用酶介导的酯交换或水解。一些报道已经出现了非酶的方法，可以广泛的通用，允许制备适合有机化合物分子库的量身定制的手性构建块。以n -甲酰基-(L)-萘丙氨酸衍生的恶唑硼烷酮介导的对映选择性切环反应为关键反应，实现了2-取代1,3-丙二醇的非酶解对称反应，得到了对映异构富集的3-苄基氧基-1-丙醇。发现该方法对2位上有较大取代基的丙二醇非常有效。进一步考察反应条件，减少恶唑硼烷酮的用量，表明使用乙醚作为添加剂是有效的。在添加剂存在的情况下，即使使用0.5等量的奥氨波罗啶酮，也能实现高选择性的环裂解反应。除此之外，使用二甲基硅基烯酮S， o -缩醛作为亲核试剂也被发现对催化对映选择性环裂解反应有效。