Tetrodotoxin, synthesis

Tebbe reaction 148 Tetracyclin synthesis 190 Tetrazole synthesis 17 Tetrodotoxin synthesis 136 Tocopherol synthesis 142 Tonantzitlolone synthesis 188 Triazine synthesis 17 Triclavulone synthesis 102... 

A more complex example is seen in Kishi s tetrodotoxin synthesis.Enol ether (76) provided the precursor to a-acetoxy ketone (77), which was obtained as a single stereoisomer by acetic acid opening of the initial ethoxy epoxide. 

Tetrazolo[5,1 -6][ 1,2,4]triazin-3-ones synthesis, 3, 392 Tetrazolyl radicals oxidation, 5, 60 Tetrazolyl ylides structure, 5, 793 Tetrenolin occurrence, 4, 706 Tetrodotoxin... 

The signature application for the G-H insertion in synthesis is probably the total synthesis of (—)-tetrodotoxin 126 by Du Bois and Hinman.233 Two stereospecific G-H activation steps, rhodium-catalyzed carbene G-H insertion and carbamate-based nitrene C-H insertion, have been used to install the two tetrasubstituted centers C6 and C8a (Scheme 12). Diazoketone 122 was treated with 1.5mol% Rh2(HNCOCPh3)4, and cyclic ketone 123 was selectively formed in high yield without purification. The reaction of carbamate 124 with 10mol% Rh2(HNCOCF3)4, PhI(OAc)4, and MgO in C6H6 solvent furnished the insertion product 125 in 77% yield. 

Recently, a synthesis of tetrodotoxin from D-glucose was described (Scheme 36). After a Michael addition of the lithium salt of bis(phenylthio)-methane to the nitroolefin 116, the major component (117b) of the resulting epimeric mixture 117a + 117b was subjected to a reaction sequence that involved an intramolecular nitroaldol reaction, to give the complex nitro cyclohexane derivative 118. 

Ohyabu N, Nishikawa T, Isobe M, First asymmetric total synthesis of tetrodotoxin,/Aw Chem Soc 125 8798—8805, 2003. 

Sato K, Akai S, SugitaN, OhsawaT, KogureT, Shoji H, Yoshimura J, Novel and stereo controlled synthesis of ( )-tetrodotoxin from myo-inositol, / Org Chem 70 7496-7504, 2005. 

II. A stereospecific synthesis of a compound having the same six chiral centers on the cyclohexane ring as those of tetrodotoxin, Tetrahedron Lett., 11 (1970) 5129-5132. 

Justin Du Bois of Stanford University has put forward (J. Am. Chem. Soc. 2003,125, 11510) a quite different total synthesis of tetrodotoxin, including an elegant late-stage introduction of the nitrogen. 

M. Funabashi, H. Wakai, K. Sato, and J. Yoshimura, Branched-chain sugars. Part 15. Synthesis of l-i.-(l,2,3, 4,5/3,6)-3-hydroxymethyl-4,5-0-isopropylidene-3,3 -0-methylene-6-nitro-2,3,4,5-tetrahydrocyclohexanecarbaldehyde dimethyl acetal, a potential key compound for total synthesis of optically active tetrodotoxin, J. Chem. Soc. Perkin Trans, p. 14 (1980). 

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