C5-C10 directly bonded tetrodotoxin analogues: possible biosynthetic precursors of tetrodotoxin from newts.
The identification of novel tetrodotoxin (TTX, 1) analogues would significantly contribute to the elucidation of its biosynthetic pathway. In this study, the first C5-C10 directly bonded TTX analogues, 4,9-anhydro-10-hemiketal-5-deoxyTTX (2) and 4,9-anhydro-8-epi-10-hemiketal-5,6,11-trideoxyTTX (3), were found in the newt Cynops ensicauda popei by using a screening method involving HILIC-LC-MS/MS focused on the fragment ions of TTX analogues, and their structures were elucidated by spectroscopic methods. Compound 2 was detected in a wide range of newt species, and the 2 and TTX contents of 22 newt specimens were correlated (rs =0.88). Based on these results and its structural features, 2 was predicted to serve as a precursor of TTX that would be directly converted into 4,9-anhydroTTX (4) by Baeyer-Villiger-like oxidation or via 4,9-anhydro-5-deoxyTTX formed by cleavage of the C5-C10 bond. The bicyclic carbon skeletons of 2 and 3 suggested a possible monoterpene origin for TTX.
Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi, 981-8555 (Japan).
Yuta
Y
Kudo
Yoko
Y
Yamashita
Dietrich
D
Mebs
Yuko
Y
Cho
Keiichi
K
Konoki
Takeshi
T
Yasumoto
Mari
M
Yotsu-Yamashita
D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism; D002244:Carbon / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D012455:Salamandridae / Q000378:metabolism*; D013779:Tetrodotoxin / Q000031:analogs & derivatives* / Q000096:biosynthesis
D001688:Biological Products; D013779:Tetrodotoxin; D002244:Carbon
biosynthesis; mass spectrometry; natural products; structure elucidation; tetrodotoxin