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

这项研究旨在开发有用的手性合成子（氨基手性合成子），该合成子应该在合成各种生物活性生物碱方面受欢迎。这些氨基手性合成子需要的是安装与此类生物活性物质有关的氮原子附近的定义立体中心。我们认为，与此必要的匹配的可能的起始材料是光学活跃的α-氨基酸，并且通过其功能组转化而引起了原本无法访问的氨基手性合成的发展。在这种情况下，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群的完整性，那么最重要的一点是我们如何通过适当减少α-氨基酸的α-氨基醇或可衍生的氨基醛来详细说明新颖的氨基手性合成。到（1）将氨基Alco的转换为循环硫酸盐，将其转变为咪达顿离子的转化，以及将imidatonium离子提交给新颖的核philic环开放过程，以及（2）合成手性胺或4-氨基氨基的氨基氨基含量的氨基氨基含量。我们对这些目的的努力得到了一些富有成果的结果。关于目标（1），我们成功地建立了一种新型的非构态方法，用于通过依靠合理选择的核离子选择来通过核离子环的开口来合成酰胺。关于（2），由Nozaki-Ohshima开发的非基本有机试剂提供了一种解决方案，可以在不进行种族化的情况下从氨基醛中提供各种Allyl胺，此外，我们发现了4-氨基 - α-α-α-β-未饱和酯可以在1,2-FORNASENS中能够减少beta-amino-alpha，从而使Chiral 4-AmiNONICONALY FORNALLALY 4--氨基酸含量可以减少。那种被赋予的氨基手性合成子已成功用于天然生物碱的合成和某些生物学利益的氮化合物。较少的