Cyclic Guanidine Compounds From Newts Support the Hypothesis that Tetrodotoxin is Derived From Monoterpene
Cyclic Guanidine Compounds From Newts Support the Hypothesis that Tetrodotoxin is Derived From Monoterpene
复制标题
来自蝾螈的环状胍化合物支持河豚毒素源自单萜的假设
DOI：
10.1002/ange.201602971
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
and Mari Yotsu-Yamashita*
中科院分区：
文献类型：
--
作者：
Yuta Kudo;Takeshi Yasumoto;Dietrich Mebs;Yuko Cho;Keiichi Konoki;and Mari Yotsu-Yamashita*
河豚毒素(TTX)是一种由2，4-二氧金刚烷骨架和胍基组成的强效神经毒素，其生物合成是天然产物化学中一个悬而未决的问题。最近，第一个C5-C10直接键合的TTX类似物4，9-脱水-10-半酮-5-脱氧TTX被从有毒的蝾螈中得到，它的碳骨架表明它可能是单萜的来源。在这一假设的基础上，使用两种MS引导的方法对TTX的预测生物合成中间体进行筛选。本论文报道了五种新的从有毒鳗鱼中提取的环胍类化合物，它们通常含有酰基稠合的双环结构，其中包括一个六元的环胍。这些结构可以通过氧化、环化和/或异构化步骤从香叶基胍生物合成而来。LC-MS分析证实了这五种新化合物在有毒蝾螈中的广泛分布。这些结果支持TTX来源于单萜的假设。
The biosynthesis of tetrodotoxin (TTX), a potent neurotoxin consisting of a 2,4‐dioxaadamantane skeleton and a guanidine moiety, is an unsolved problem in natural product chemistry. Recently, the first C5–C10 directly bonded TTX analogue, 4,9‐anhydro‐10‐hemiketal‐5‐deoxyTTX, was obtained from toxic newts and its carbon skeleton suggested a possible monoterpene origin. On the basis of this hypothesis, screening of predicted biosynthetic intermediates of TTX was performed using two MS‐guided methods. Herein, five novel cyclic guanidine compounds from toxic newts are reported which commonly contain acis‐fused bicyclic structure including a six‐membered cyclic guanidine. These structures could be biosynthetically derived from geranyl guanidine through oxidation, cyclization, and/or isomerization steps. LC–MS analysis confirmed the widespread distribution of the five novel compounds in toxic newt species. These results support the hypothesis that TTX is derived from a monoterpene.