Stereocontrolled Synthesis and Activity of multi-oxygenated Marine Natural Products

一些海洋天然产品被作为海产品，偶尔会污染一些影响人体健康的天然产品。从分子科学的角度进行了相应的研究。这些海洋天然产物以河豚毒素和雪卡毒素为代表。首先，从鱼浆杆中提取第1例TTX及其类似物，TTX结晶母液中有各种类似物，采用混合型纳米lc - esi - q - tof - ms分析仪，采用水介质和氧化氘离子交换柱进行比较。利用LC-MS的氘交换技术，约有20个峰被指定为TTX的类似物，该技术提供了TTX类似物氧或氮原子上可交换质子的明确数量。另一方面，在本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。试图对另一种天然产物CTX进行全合成，部分成功地合成了CTX的左手部分和80%的右手部分的CTX分子。该方法包括Isobe课题组独创的综合方法和概念；因此，糖乙炔，乙炔的二钴二羰基配合物，这些配合物的酸性环化利用，将环化的配合物转化为乙烯基硅烷，并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存在，但基本上已经实现了最初的计划。后合成项目已初步建立了适用于TTX、CTX类海洋化合物的蛋白质体系。

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.