Synthesis of 5,6,11-Trideoxytetrodotoxin

Abstract

5,6,11-Trideoxytetrodotoxin, a naturally occurring analog of tetrodotoxin, was synthesized from a synthetic intermediate of 5-deoxytetrodotoxin by continuous radical deoxygenation of two hydroxy groups at the C-6 and C-11 positions.

Differential binding of tetrodotoxin and its derivatives to voltage‐sensitive sodium channel subtypes (Nav1.1 to Nav1.7)

“…TTX (1) (Ohyabu et al, 2003;Nishikawa et al, 2004;Urabe et al, 2006), CHTX (2) (Adachi et al, 2014a), 8-deoxyTTX (3) (Satake et al, 2014), 4,9-anhydroTTX (4) (Ohyabu et al, 2003;Nishikawa et al, 2004;Urabe et al, 2006), 4,9-anhydroCHTX (5), 4,9-anhydro-8-deoxyTTX (6), 5-deoxyTTX (7) (Satake et al, 2014), 5,11-dideoxyTTX (8) (Nishikawa et al, 1999;Asai et al, 2001;Yotsu-Yamashita et al, 2013), 5,6,11-trideoxyTTX (9) (Adachi et al, 2014b), 4,9-anhydro-5-deoxyTTX (10) (Satake et al, 2014), 4,9-anhydro-5,11-dideoxyTTX (11) (Nishikawa et al, 1999;Asai et al, 2001;Yotsu-Yamashita et al, 2013) and 4,9-anhydro-5,6,11-trideoxyTTX (12) (Adachi et al, 2014b) were synthesized as reported in the literature (Figure 1 KOD-Plus, T4 ligase and the In-Fusion HD Cloning kit were purchased from Takara Bio, Inc. (Kusatsu, Shiga, Japan). PCR primers were purchased from Fasmac Co., Ltd. (Atsugi, Kanagawa, Japan).…”

Tetrodotoxin: History, Biology, and Synthesis

“…The enantioselective syntheses of 5,11‐dideoxyTTX, 11‐deoxyTTX, and 8,11‐dideoxyTTX were achieved before the synthesis of (−)‐TTX and feature the synthesis of the natural product based on a Diels–Alder strategy from levoglucosenone. The same approach also gave rise to the syntheses of 5,6,11‐trideoxyTTX, 5‐ and 8‐deoxyTTX later. The other synthesis of 5,6,11‐trideoxyTTX was reported by Ohfune and Shinada .…”

“…Recently, the alkaloids 22 and 400 (as well as 23 ) have been synthesized by Nishikawa and Isobe from acetal 410 , an O ‐ethyl analogue of compound 365 (cf. Section 6.1.2), by consecutive radical deoxygenation of two hydroxyl groups at the carbons C‐6 and C‐11, Scheme .…”

“…Total synthesis of (−)‐ 23 as well as of C‐10‐labeled 23 was published by Ohfune, Shinada and co‐workers in 2006. Isobe and Nishikawa later also published synthesis of (−)‐ 23 , see preceding Section 6.1.6.…”

Tetrodotoxin: Geschichte, Biologie und Synthese

“…Die enantioselektiven Synthesen von 5,11‐DideoxyTTX, 11‐DeoxyTTX und 8,11‐DideoxyTTX gelangen vor der Synthese von (−)‐TTX und zeichnen sich durch die Synthese des Naturstoffs basierend auf einer Strategie über eine Diels‐Alder‐Reaktion von Levoglucosenon aus. Aus derselben Vorgehensweise gingen später auch die Synthesen von 5,6,11‐TrideoxyTTX, 5‐ und 8‐DeoxyTTX hervor. Eine weitere Synthese von 5,6,11‐TrideoxyTTX wurde von Ohfune und Shinada berichtet .…”