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OH
O
H
•
O
O
N
S
H
S
AcO
OH
1
•
O
O
a, b
2
AcO
OH
21
e
d
15
OH
H
O
•
c
3
OHC
O
AcO
OH
O
O
O
22
O
23
HO
Scheme 6. Total synthesis of 1: a) 2-mercaptobenzothiazole, PPh3, DIAD, THF, room temperature, 1.5 h (78%); b) (NH4)6Mo7O24 ¥ 4H2O, H2O2 (aq. 30%),
EtOH, 08C, 1 h (89%); c) MnO2, diethyl ether, room temperature, 5 min; d) NaHMDS, THF, À788C, 5 min, in the dark (50% from 22, E/Z 1:3); e) C6H6,
258C, 3 d, in the dark (E/Z > 5:1); preparative HPLC purification. DIAD diisopropyl azodicarboxylate, NaHMDS sodium bis(trimethylsilyl)amide,
HPLC high-performance liquid chromatography.
[1] F. Schutt, Ber. Dtsch. Bot. Ges. 1890, 8, 9.
[2] a) H. A. Frank, R. J. Cogdell in Carotenoids in Photosynthesis (Eds.:
temperature, and the resulting mixture was stirred for 20 h. As
expected, we obtained the desired ylidenebutenolide 3 in
49% yield as a single stereoisomer. Sonogashira coupling of
18 with 11, reductive deallylation,[19] and highly stereoselec-
A. Young, G. Britton), Chapman & Hall, London, 1993; b) E.
Hofmann, P. M. Wrench, F. P. Sharples, R. G. Hiller, W. Welte, K.
Diederichs, Science 1996, 272, 1788.
tive intramolecular lactonization proceeded successfully via
19 in one pot[20] by the successive action of Pd0 and PdII
catalysts.
[3] a) H. H. Strain, W. A. Svec, K. Aitzetmuller, M. C. Grandolfo, J. J.
Katz, H. Kjosen, S. Norgard, S. Lieean-Jensen, F. T. Haxo, P. Wegfahrt,
H. Rapoport, J. Am. Chem. Soc. 1971, 93, 1823; b) J. E. Johansen, G.
Borch, S. Lieean-Jensen, Phytochemistry 1980, 19, 441.
The final step in the synthesis of peridinin was the coupling
of 2 and 3. After several trials, we knew that the halides
derived from the C17-allene segment 2 were unstable under
the reaction conditions required for the preparation of the
corresponding Wittig salt, although the very similar C15-Wittig
salt has been reported.[20] We thus turned our attention to the
modified Julia Kocienski olefination,[21] which made the
olefination possible at a relatively lower temperature. Allene
2 was transformed into benzothiazole sulfone 21 by the
Mitsunobu reaction with 2-mercaptobenzothiazole, followed
by molybdenum(vi)-catalyzed oxidation[22] (Scheme 6). The
reaction between the sulfone group of 21 and the aldehyde
function of 22 (derived from 3) proceeded successfully within
5 min by using NaHMDS at À788C in the dark. Although the
crude product obtained was a mixture of the desired all-trans-
[4] a) Y. Yamano, M. Ito, J. Chem. Soc. Perkin Trans. 1 1993, 1599; b) M.
Ito, Y. Yamano, S. Sumiya, A. Wada, Pure Appl. Chem. 1994, 66, 939.
[5] a) T. Katsuki, K. B. Sharpless, J. Am. Chem. Soc. 1980, 102, 5976;
b) R. M. Hanson, K. B. Sharpless, J. Org. Chem. 1986, 51, 1922; c) Y.
Gao, R. M. Hanson, J. M. Klunder, S. Y. Ko, H. Masamune, K. B.
Sharpless, J. Am. Chem. Soc. 1987, 109, 5765.
[6] Y. Yamano, C. Tode, M. Ito, J. Chem. Soc. Perkin Trans. 1 1998, 2569.
[7] a) A. Schoenberg, I. Bartoletti, R. F. Heck, J. Org. Chem. 1974, 39,
3318; b) J. K. Stille, P. K. Wong, J. Org. Chem. 1975, 40, 532; c) M.
Hidai, T. Hikita, Y. Wada, Y. Furikura, Y. Uchida, Bull. Chem. Soc.
Jpn. 1975, 48, 2075.
[8] A. Baumeler, W. Brade, A. Haag, C. H. Eugster, Helv. Chim. Acta.
1990, 73, 700.
[9] E. Widmer, Pure Appl. Chem. 1985, 57, 741; alternatively, we reported
the novel synthesis of the allene moiety of carotenoids by means of
biomimetic photosensitized oxygenation: M. Nakano, N. Furuichi, H.
Mori, S. Katsumura, S. Tetrahedron Lett. 2001, 42, 7307.
[10] K. Sonogashira in Comprehensive Organic Synthesis, Vol. 3 (Eds.:
B. M. Trost, I. Fleming, G. Pattenden), Pergamon, Oxford, 1991, p. 52 1.
[11] Vinyl iodide 12 was prepared from the commercially available
2-butyn-1-ol by means of stannylcupration with nBu3Sn(nBu)CuCN-
Li2 (B. H. Lipshutz, J. A. Kozlowski, R. S. Wilhelm, J. Org. Chem.
1984, 49, 3943) followed by tin halogen exchange.
[12] Y. Yamano, S. Sumiya, M. Ito, J. Chem. Soc. Perkin Trans. 1 1995, 167.
[13] H. Mori, H. Kubo, H. Hara, S. Katsumura, Tetrahedron Lett. 1997, 38,
5311.
[14] Original reports: a) C. Lambert, K. Utimoto, H. Nozaki, Tetrahedron
Lett. 1984, 25, 5323; b) X. Lu, X. Huang, S. Ma, Tetrahedron Lett. 1993,
34, 5963; this method was developed for natural products syntheses by
other groups: c) M. Kotora, E. Negishi, Tetrahedron Lett. 1996, 37,
9041; d) F. Liu, E. Negishi, J. Org. Chem. 1997, 62, 8591; e) M. Kotora,
E. Negishi, Synthesis 1997, 121; f) E. Negishi, M. Kotora, Tetrahedron
1
peridinin (1) and its 15-cis isomer 23 (1:3 based on H NMR
spectroscopic analysis), we found that the Z isomer was
converted into the thermodynamically more stable E isomer
in a solution of benzene at room temperature in the dark after
1
3 days (E/Z > 5:1 based on H NMR spectroscopic analysis
and analytical HPLC). The desired enantiomerically pure
peridinin (1) was obtained after purification by means of
preparative HPLC in the dark. The spectral data of the
synthetic peridinin were in good agreement with those
reported.[3, 4]
Received: November 16, 2001 [Z18233]
Angew. Chem. Int. Ed. 2002, 41, No. 6
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