Synlett 2004(4): 603-608  
DOI: 10.1055/s-2004-817769
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Synthesis of the Fully Functionalized HIJ-ring Framework of Ciguatoxin

Takayuki Baba, Shigeyuki Takai, Naotaka Sawada, Minoru Isobe*
Laboratory of Organic Chemistry, School of Bioagricultural Sciences, Nagoya University
Fax: +81(52)7894111; e-Mail: isobem@agr.nagoya-u.ac.jp;
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Publikationsverlauf

Received 18 December 2003
Publikationsdatum:
10. Februar 2004 (online)

Abstract

An efficient convergent synthetic route to construct the HIJ-ring system of ciguatoxin was achieved via stereo controlled eight-membered ring formation by using acetylene cobalt complex and subsequent six-membered ring formation through intramolecular 1,4-addition reaction.

11

Physical data for 7a. 1H NMR (400 MHz, CDCl3): δ = 1.39 (1 H, q, J = 11.0 Hz, H-43a), 1.84 (1 H, br, -OH), 2.58 (1 H, dd, J = 15.5, 9.0 Hz, H-40a), 2.61 (1 H, dt, J = 11.0, 4.0 Hz, H-43b), 2.92 (1 H, dd, J = 15.5, 2.0 Hz, H-40b), 3.25-3.45 (4 H, m, H-41, H-42, H-44, H-45), 3.38 (3 H, s, -OCH 3 ), 3.39 (3 H, s, -OCH 3 ), 3.56 (1 H, dd, J = 10.5, 4.0 Hz, H-46a), 3.64 (1 H, dd, J = 10.5, 1.5 Hz, H-46b). HRMS (FAB) calcd for C12H20F3O7S+ [M + H]+: 365.0882. Found: 365.0872.

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Physical data for 6. 1H NMR (300 MHz, CDCl3): δ = 1.10, 1.11 (3 H, s, -CH3), 1.37, 1.38 [3 H, s, -C(CH 3 )2], 1.46 [3 H, s, -C(CH 3 )2], 1.78-1.90 (total 1 H, m, H-35a), 1.95, 2.07 (total 1 H, ddd, J = 14.5, 5.0, 2.5 Hz and J = 14.5, 4.0, 2.0 Hz, H-35b), 2.50-2.61 (total 2 H, m, H-36, acetylene), 2.78, 2.84 (total 1 H, dd, J = 17.0, 3.5 Hz and J = 17.5, 3.0 Hz, H-31), 3.03, 3.22 (total 1 H, br-s, -OH), 3.82, 4.10 (total 1 H, dd, J = 10.0, 2.0 Hz and J = 10.0, 2.5 Hz, H-34), 4.22, 4.29 (total 1 H, dd, J = 9.5, 3.0 Hz and J = 9.0, 3.5 Hz, H-32), 4.64, 4.75 (total 1 H, m, H-36). Anal. Calcd for C13H19NO4: C, 61.64; H, 7.56; N, 5.53. Found: C, 61.65; H, 7.51; N, 5.43.

16

Physical data for 20. 1H NMR (400 MHz, CDCl3) δ = 1.34 (3 H, s, H-56), 1.40 (1 H, q, J = 11.5 Hz, H-43a), 1.93 (1 H, q, J = 11.5 Hz, H-35a), 2.50 (1 H, dt, J = 11.5, 5.0 Hz, H-35b), 2.53 (1 H, ddd, J = 11.5, 4.5, 4.0 Hz, H43b), 2.60 (1 H, dd, J = 17.0, 4.0 Hz, H-31a), 2.62 (1 H, dd, J = 17.0, 8.0 Hz, H-31b), 2.69 (1 H, ddd, J = 11.0, 4.0, 2.0 Hz, H-38a), 2.79-2.89 (3 H, m, H-38b, H-40a, H-40b), 3.21 (1 H, d, J = 8.0 Hz, -OH), 3.20-3.26 (2 H, m, H-44, H-45), 3.32 (1 H, ddd, J = 11.5, 9.5, 4.5 Hz, H-42), 3.34 (3 H, s, -OCH 3), 3.38 (3 H, s, -OCH 3), 3.43 (1 H, ddd, J = 11.5, 9.5, 5.0 Hz, H-36), 3.48 (1 H, ddd, J = 10.5, 9.5, 4.5 Hz, H-41), 3.53 (1 H, dd, J = 10.5, 4.0 Hz, H-46b), 3.61 (1 H, dd, J = 10.5, 1.5 Hz, H-46b), 3.74 (1 H, td, J = 8.0, 4.0 Hz, H-32), 3.75 (1 H, ddd, J = 10.5, 9.5, 4.0 Hz, H-37), 5.40 (1 H, dd, J = 12.0, 5.0 Hz, H-34), 7.45-7.52 (2 H, m, aromatic), 7.60-7.64 (1 H, m, aromatic), 7.96-8.00 (2 H, m, aromatic). HRMS (FAB) calcd for C27H35NNaO9 + [M + Na]+: 540.2210. Found: 540.2180.

19

Physical data for 29. 1H NMR (400 MHz, CDCl3) δ = 0.89-1.06 {21 H, m, -Si[CH(CH 3)2]3}, 1.07 (3 H, d, J = 7.0 Hz, CH3-57), 1.33 (1 H, m, H-43a), 1.45-1.71 (2 H, m, H-38a, H-40a), 1.47 (3/2 H, s, H-56), 1.49 (3/2 H, s, H-56*), 1.72-1.80 (1 H, m, H-35a), 1.82-2.09 (3 H, m, H-38b, H-39, H-40b), 2.48-2.57 (3 H, m, H-31a, H-35b, H-43b), 2.82 (1/2 H, dd, J = 16.5, 5.5 Hz, H-31b), 2.89 (1/2 H, dd, J = 16.5, 5.5 Hz, H-31b*), 3.10-3.66 (6 H, m, H-36, H-37, H-41, H-42, H-44, H-45), 3.35 (3 H, s, -OCH 3) 3.40 (3 H, s, -OCH 3), 3.49 (1 H, dd, J = 10.5, 5.5 Hz, H-46a), 3.63 (1 H, dd, J = 10.5, 2.0 Hz, H-46b), 3.97 (1/2 H, t, J = 5.5 Hz, H-32), 4.05 (1/2 H, dd, J = 5.5, 4.5 Hz, H-32*), 5.15 (1 H, dd, J = 11.5, 4.5 Hz, H-34), 7.44-7.49 (2 H, m, aromatic), 7.58-7.62 (1 H, m, aromatic), 7.99-7.02 (2 H, m, aromatic). The fractional integral values result from the existence of a rotational isomer at C32-C33 bond. HRMS (FAB) calcd for C37H59O8NNaSi+ [M + Na]+: 696.3907. Found: 696.3917.