Studies on the synthesis of biologically active alkaloids employing chiral oxazoline blocks

手性恶唑啉嵌段合成生物活性生物碱的研究

基本信息

批准号：
59550597
负责人：
MORIWAKE Toshio
金额：
$ 1.28万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C).
财政年份：
1984
资助国家：
日本
起止时间：
1984 至 1985
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-59550597/
关键词：
Chiral Oxazoline Amino Acids Biologically Active Alkaloids Cyclic Imidates Amide Synthesis Chiral Allyl Amines gamma-Amino Allylic Alcohols Amino Chiral Synthons

项目摘要

This research aims at developing useful chiral synthons (amino chiral synthons) which should enjoy large popularity in synthesizing various bioactive alkaloids. What is required for these amino chiral synthons is the installation of definite stereocenters adjacent to nitrogen atoms involved in such biologically active substances. We have considered that a possible starting material matching to this requisite is optically active alpha-amino acids and have been intrigued with the development of otherwise inaccessible amino chiral synthons through their functional-group transformation. In this context we must recognize that if we want to keep their stereochemical integrity and amino groups intact throughout the course of the transformation, the most important points is how we can elaborate novel amino chiral synthons from amino alcohols or amino aldehydes derivable via appropriate reduction of alpha-amino acids. Accordingly we have fixed our attention to(1)the conversion of the amino alco … More hols to cyclic imidates, their transformation to imidatonium ions, and submission of the imidatonium ions to novel nucleophilic ring opening processes, and(2)synthesis of chiral allyl amines or 4-aminoallylic alcohols from the amino aldehydes without racemization. Our efforts toward these ends have been rewarded with some fruitful results. With regard to the objective(1), we have succeeded in establishing a novel non-condensative method for synthesizing amides by nucleophilic ring opening of the imidates relying on reasonable choice of nucleophiles. With regard to(2) , non-basic organometallic reagent developed by Nozaki-Ohshima gave a solution to give various allyl amines from the amino aldehydes without racemization and, in addition, we have found the reaction conditions under which 4-amino-alpha, beta-unsaturated esters can be reduced in a 1,2-fashion to give chiral 4-aminoallylic alcohols. Thus-obtained amino chiral synthons have been successfully employed for the syntheses of natural alkaloids and some nitrogen compounds of biological interests. Less

这项研究的目标是有用的手性合成子（氨基手性合成子），这些合成子在合成各种生物活性生物碱中应该受到广泛欢迎，这些氨基手性合成子所需的是与此类生物活性物质中涉及的氮原子相邻的确定的立体中心。认为符合这一要求的可能起始材料是光学活性α-氨基酸，并且对通过官能团转化开发其他难以获得的氨基手性合成子很感兴趣。我们必须认识到，如果我们想在整个转化过程中保持其立体化学完整性和氨基完整，最重要的一点是我们如何从通过适当还原α-氨基衍生的氨基醇或氨基醛中精心设计新型氨基手性合成子因此，我们将注意力集中在（1）氨基醇向环状亚氨酸盐的转化、它们向亚米达鎓离子的转化以及亚米达鎓离子向新型化合物的转变。亲核开环过程，以及（2）从氨基醛合成手性烯丙胺或4-氨基烯丙醇，而无需外消旋作用。我们为实现这些目标所做的努力已经获得了一些丰硕的成果。依靠合理选择亲核试剂，成功建立了一种通过亚胺酸酯亲核开环合成酰胺的新型非缩合方法。到（2），野崎大岛开发的非碱性有机金属试剂提供了一种溶液，可以从氨基醛得到各种烯丙胺而不需要外消旋，此外，我们还发现了4-氨基-α，β-的反应条件。不饱和酯可以1,2-方式还原得到手性4-氨基烯丙醇，由此获得的氨基手性合成子已成功用于天然生物碱和一些具有生物学意义的氮化合物的合成较少。