权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Preparation of Physalins Possessing High Antitumor Activity

具有高抗肿瘤活性的酸浆素的制备

基本信息

批准号：
01550666
负责人：
KAWAI Masao
金额：
$ 1.15万
依托单位：
Nagoya Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

Physalin N and physalin O were isolated from the extracts of epigeal part of Physalis alkekengi var. francheti (Japanese name : Hozuki). Based on ^1H and ^<13>C NMR spectral analysis physalin N was assumed to be 7alphaーhydroxy1 derivative of physalin B. Similarly, physalin O was assumed to be 25, 27-dihydro derivative of physalin A. Upon catalytic hydrogenation physalin O gave the expected 7-dehydroxyー2, 3, 5, 6, 25, 27-hexahydrophysalin A, and acidーcatalyzed dehydration of physalin O afforded 2, 7-didehydrophysalin M, the already known dehydration product of physalin L. Thus, the structure of physalin O has been established as (25S)-25, 27-dihydrophysalin A unequivocally. Another constituent, tentatively named physalin P, was also isolated and its ^<13>C NMR spectra indicated that physalin P did not possess usual physalin skeleton but the rearranged structure called neophysalin skeleton. NMR, UV, and CD spectral analyses and the chemical transformation to the known 4, 7-didehydroneophysalin B have established the structure of physalin P to be 5alpha-hydroxy-6, 7-didehydro-5, 6-dihydroneophysalin B.Antitumor activities of physalins and their derivatives were tested against HeLa cells, and the following structure-activity relationships have been proposed : i) Conjugated cyclohexenone at ring A is very important to the activity. ii) alpha-Hydroxy and alpha-epoxy groups at ring A or B markedly decrease the activity. iii) beta-hydroxy and beta-epoxy groups at ring A increase or do not affect the activity. Importance of methylene oxide bridge C(14)-O-C(27) and double bond C(25)=C(27) and of physalin skeleton are not certain.Molecular design and synthetic approach towards the preparation of highly active physalins based on the above structure-activity relationship are being undertaken.

从酸浆上腹部提取液中分离得到酸浆蛋白N和酸浆蛋白O。加盟商(日文名称：Hozuki)。根据^1H和^&lt；13&gt；cNMR谱分析，假设酸枣仁素N是酸枣仁素B的7αー羟基1衍生物。类似地，酸枣仁素O被假定为酸枣仁素A的25，27-二氢衍生物。酸酸碱酯O催化氢化得到预期的7-脱羟基ー2，3，5，6，25，27-六氢酸枣仁素A，而酸ー催化酸枣仁素O脱水得到已知的酸枣仁素L的脱水产物2，7-二氢酸茶素M，从而确定其结构为(25S)-25，27-二氢酸碱酯A。另一组分，暂定名为酸浆蛋白P，其核磁共振波谱表明，酸浆蛋白P不具有普通的酸浆蛋白骨架，而是一种重排结构，称为新藻糖素骨架。通过对已知的4，7-二氢叶黄素B进行了核磁共振、紫外和圆二色谱分析，确定了其结构为5α-羟基-6，7-二氢-5，6-二氢叶黄素B。研究了其衍生物对HeLa细胞的抗肿瘤活性，提出了如下构效关系：1)A环共轭环己酮对活性非常重要。Ii)A或B环上的α-羟基和α-环氧基显著降低活性。Iii)环A上的β-羟基和β-环氧基增加或不影响活性。亚甲基氧桥C(14)-O-C(27)和双键C(25)=C(27)的重要性以及酸浆骨架的重要性尚不确定，基于上述构效关系的分子设计和合成方法正在进行中。