First asymmetric total synthesis of tetrodotoxin

Journal of the American Chemical Society

Volumn 125, Issue 29, 2003, Pages 8798-8805

  Ohyabu, Norio ^a   Nishikawa, Toshio ^a   Isobe, Minoru ^a  

^a NAGOYA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ENANTIOMERS;

CHROMATOGRAPHIC ANALYSIS; ETHERS; ION EXCHANGE; MARINE BIOLOGY; MOLECULAR STRUCTURE; NITROGEN; SYNTHESIS (CHEMICAL);

TOXIC MATERIALS;

TETRODOTOXIN;

ARTICLE; CHEMICAL STRUCTURE; ION EXCHANGE CHROMATOGRAPHY; REACTION ANALYSIS; STEREOCHEMISTRY; STRUCTURE ANALYSIS; SYNTHESIS;

CYCLOHEXANES; LACTONES; OXIDATION-REDUCTION; STEREOISOMERISM; TETRODOTOXIN;

EID: 0038637028     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja0342998     Document Type: Article

References (97)

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30. The compound 5 is an ortho ester form of a tetrodamine intermediate named by Kishi. See ref 10.
31. This problem was mentioned in Kishi's total synthesis; see ref 10.
32. Since the problem was encountered in the synthesis of (-)-5,11-dideoxytetrodotoxin, we devised intramolecular acetal between the hydroxyl group at the C-9 position and aldehyde at the C-4 position to protect the labile C-9 position. See ref 13.
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59. 1H NMR spectra of 32.
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84. Triethylamine was required for benzoylation of the ortho ester. In the absence of the amine, only the primary alcohol at the C-11 position was benzoylated.
85. Protection of the hydroxyl group at the C-8 position prevented from participation of the hydroxyl group to the proximate Boc group, leading to cyclic carbamate.
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90. 1H NMR spectra in each measurement, presumably because 57 might exist as a mixture of guanidine and guanidinium forms.
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97. 2O). Synthetic 1 showed a fatal toxicity with a mouse (ip) test.