TY - JOUR
T1 - Synthesis of 5- and 8-deoxytetrodotoxin
AU - Satake, Yoshiki
AU - Adachi, Masaatsu
AU - Tokoro, Shouta
AU - Yotsu-Yamashita, Mari
AU - Isobe, Minoru
AU - Nishikawa, Toshio
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/7
Y1 - 2014/7
N2 - Tetrodotoxin, a toxic principle of puffer fish intoxication, is one of the most famous marine natural products owing to its complex structure and potent biological activity, which leads to fatal poisoning. Continuous synthetic studies on tetrodotoxin and its analogues to elucidate biologically interesting issues associated with tetrodotoxin have led to the development of versatile routes for a variety of tetrodotoxin derivatives. With the aim of investigating the structure-activity relationship of tetrodotoxin with voltage-gated sodium channels, this study describes the first total syntheses of 5-deoxytetrodotoxin, a natural analogue of tetrodotoxin, and 8-deoxytetrodotoxin, an unnatural analogue, from a newly designed, versatile intermediate in an efficient manner. An estimation of the biological activities of these compounds reveals the importance of the hydroxy groups at the C-5 and C-8 positions on the inhibition of voltage-gated sodium channels. Close the gate! The 5- and 8-deoxytetrodotoxins are synthesized from a newly designed versatile intermediate for a wide variety of analogues of tetrodotoxin. Estimation of the biological activities of these compounds reveals the importance of the hydroxy groups of the C-5 and C-8 positions on the inhibition of voltage-gated sodium channels.
AB - Tetrodotoxin, a toxic principle of puffer fish intoxication, is one of the most famous marine natural products owing to its complex structure and potent biological activity, which leads to fatal poisoning. Continuous synthetic studies on tetrodotoxin and its analogues to elucidate biologically interesting issues associated with tetrodotoxin have led to the development of versatile routes for a variety of tetrodotoxin derivatives. With the aim of investigating the structure-activity relationship of tetrodotoxin with voltage-gated sodium channels, this study describes the first total syntheses of 5-deoxytetrodotoxin, a natural analogue of tetrodotoxin, and 8-deoxytetrodotoxin, an unnatural analogue, from a newly designed, versatile intermediate in an efficient manner. An estimation of the biological activities of these compounds reveals the importance of the hydroxy groups at the C-5 and C-8 positions on the inhibition of voltage-gated sodium channels. Close the gate! The 5- and 8-deoxytetrodotoxins are synthesized from a newly designed versatile intermediate for a wide variety of analogues of tetrodotoxin. Estimation of the biological activities of these compounds reveals the importance of the hydroxy groups of the C-5 and C-8 positions on the inhibition of voltage-gated sodium channels.
KW - asymmetric synthesis
KW - ion channels
KW - natural products
KW - structure-activity relationships
KW - total synthesis
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U2 - 10.1002/asia.201402202
DO - 10.1002/asia.201402202
M3 - Article
C2 - 24861489
AN - SCOPUS:84903158088
VL - 9
SP - 1922
EP - 1932
JO - Chemistry - An Asian Journal
JF - Chemistry - An Asian Journal
SN - 1861-4728
IS - 7
ER -