Cyclic Guanidine Compounds from Toxic Newts Support the Hypothesis that Tetrodotoxin is Derived from a Monoterpene. Issue 30 (1st June 2016)

• Record Type: Journal Article
• Authors: Kudo, Yuta; Yasumoto, Takeshi; Mebs, Dietrich; Cho, Yuko; Konoki, Keiichi; Yotsu‐Yamashita, Mari
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 30(2016)
• Page Start: 8728
• Page End: 8731
• Publication Date: 2016-06-01
• Subjects: biosynthesis -- mass spectrometry -- natural products -- structure elucidation -- tetrodotoxin; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201602971
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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 a cis ‐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. Abstract : Eye of newt : On the basis of a proposed pathway for tetrodotoxin formation, a screening of biosynthetic intermediates was carried out. Five cyclic guanidine compounds, including Cep‐210 (see picture), were found in toxic newts, and their elucidated structures support the hypothesis that tetrodotoxin is derived from a monoterpene.