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.

一些海洋天然产物被当作海产品食用，有时会污染一些影响人类健康的天然产物。人们从分子科学的角度做了相应的研究。这些海洋天然产物以河豚毒素(TTX)和雪卡毒素(CTX)为代表。首先，从幼鱼中提取第一个实施例TTX及其类似物，TTX结晶母液得到各种类似物，通过混合型nano-LC-ESI-Q-TOF-MS分析仪进行测定。使用水介质和氧化氘开发的离子交换柱进行比较。通过氘交换的 LC-MS，大约二十个峰被指定为 TTX 的类似物，该技术提供了 TTX 类似物的氧或氮原子上的明确数量的可交换质子。另一方面，在本次资助期间合成了两种脱氧类似物；因此，5,11-二脱氧TTX和11-脱氧TTX。对另一种天然产物CTX的全合成尝试部分成功，完成了CTX左手部分以及CTX分子右手部分80%的合成。该方法包含了 Isobe 研究小组独创的 Synehtic 方法和概念；因此，糖乙炔、乙炔的六羰基二钴络合物、这些络合物的酸性环化、将环化络合物转化成乙烯基硅烷、以及明智地重复这些方法以进一步进行醚环环化。这些左右部分的耦合仍然保留，但基本上已经实现了最初的计划。后合成项目已经建立，有望适用于TTX、CTX类海洋化合物。