Stereocontrolled Synthesis and Activity of multi-oxygenated Marine Natural Products

多氧化海洋天然产物的立体控制合成及其活性

基本信息

批准号：
11460055
负责人：
ISOBE Minoru
金额：
$ 7.81万
依托单位：
NAGOYA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Some marine natural products have been taken as sea foods, which occasionally contaminate some natural products affecting human higeen. The corresponding studies have been done from the point of molecular sciences. Those marine natural products are represented by tetrodotoxin (TTX) and ciguatoxin (CTX). First of all, the first example TTX and its analogs were extracted from pupper fish lever, and the mother liquor from crystallization of TTX afforded various analogs, which were determined by a hybrid type nano-LC-ESI-Q-TOF-MS analyzer with an ion-exchange column developed with aqueous media as well as deuterium oxide for comparison. About twenty peaks were assigned to be the analogs of TTX from the LC-MS with deutrium exchange, that technology affords the clear number of exchangeable protons on oxygen or nitrogen atoms of TTX analogs. On the other hand, two deoxy analogs were synthesized during the period of this grant ; thus, 5,11-dideoxy TTX and 11- deoxy TTX.Attempted total synthesis toward another natural product CTX was partly successful to conclude the synthesis of the left hand portion of CTX as well as 80% of the right hand portion of CTX molecules. The method includes the original synehtic methodology and concept from the Isobe's research group ; thus, sugar actylene, biscobalthexacarbonyl complex of the acetylenes, acidic cyclization employment of these complex, conversion of the cyclized complex into vinyl silanes, and judicious repeat of these methods for further ether ring cyclization. The coupling of these right and left segments is remained, but mostly the initial plan has been achieved. The post synthesis project have already been set up eith protein system which is promising to be applicable to the TTX, CTX class of marine compounds.

一些海洋天然产品被视为海食品，偶尔会污染一些影响人类Higeen的天然产品。相应的研究是从分子科学点开始的。这些海洋天然产物由四毒素（TTX）和雪茄毒素（CTX）代表。首先，第一个示例TTX及其类似物是从Pupper鱼杠杆中提取的，TTX结晶的母液提供了各种类似物，由混合型Nano-Lc-si-Q-si-Q-TOF-MS分析仪确定，并用带有水性介质以及甲属氧化甲中的Ion-Exchange柱进行了离子 - 脱位仪。大约二十个峰被分配为来自LC-MS的TTX的类似物，并通过氘交换为TTX，该技术为TTX类似物的氧或氮原子提供了清晰数量的可交换质子。另一方面，在本赠款期间合成了两个脱氧类似物。因此，5,11-脱氧氧基TTX和11-脱氧TTX。对另一种天然产物CTX的总合成部分成功地结论了CTX的左手部分的合成以及CTX分子的右手部分的80％。该方法包括Isobe研究小组的原始Synehtic方法和概念；因此，乙炔的糖ectylene，酸性的二核酸酶配合物，这些复合物的酸性环化雇用，环化复合物转化为乙烯基硅烷，以及这些方法的明智重复，以进一步的醚环环化。这些左右段的耦合仍然存在，但主要是最初的计划。邮政合成项目已经建立了EITH蛋白系统，该系统有望适用于TTX，CTX类的海洋化合物。