336
S. Hosokawa et al. / Tetrahedron Letters 46 (2005) 333–337
6. Shirokawa, S.; Kamiyama, M.; Nakamura, T.; Okada,
M.; Nakazaki, A.; Hosokawa, S.; Kobayashi, S. J. Am.
Chem. Soc. 2004, 126, 13604–13605.
100ꢁC in toluene in 83% yield with a:b = 5:1 selectivity.
After separation of anomers by silica gel column chro-
matography, de-O-benzylation followed by silylation
7. (a) Tatsuta, K.; Takahashi, M.; Tanaka, N. Tetrahedron
Lett. 1999, 40, 1929–1932; (b) Asami, Y.; Ogura, T.;
Otake, N.; Nishimura, T.; Xinsheng, Y.; Sakurai, T.;
Nagasawa, H.; Sakuda, S.; Tatsuta, K. J. Nat. Prod. 2003,
66, 729–731.
0
gave the glucoside 18 (J1 ,2 = 4Hz, J2 ,3 = 4Hz,
0
0
0
0
0
0
0
0
0
J2 ,4 = 1Hz, J3 ,4 = 0Hz, J4 ,5 = 9Hz). De-N-protection
of 18 with methylhydrazine gave the O-glucosylhydroxy-
amine 19. Finally, condensation of 2 with 19 followed by
de-O-protection afforded trichostatin D (1), which was
identical in all respects with the natural product.11–13
Additionally, we synthesized 6-epi-trichostatin D 21 by
coupling of (ꢀ)-trichostatic acid 2014 with the O-glucos-
ylhydroxyamine 19. It was found that the optical
8. Crystallographic data (excluding structure factors) for the
structures in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplemen-
tary publication numbers CCDC 249741 for 8, CCDC
249740 for 9a, CCDC 249742 for 9b, and CCDC 249438
for (6R,6S)-isomer of 9b. Copies of the data can be
obtained, free charge, on application to CCDC, 12 Union
Road, Cambridge, CB2 1EZ, UK [fax: +44(0)-1223-
9. Wolfe, J. P.; Tomori, H.; Sadighi, J. P. Z.; Yin, J.;
Buchwald, S. L. J. Org. Chem. 2000, 65, 1158–1174.
10. Stolberg, M. A.; Mosher, Wm. A.; Wagner-Jauregg, T. S.
J. Am. Chem. Soc. 1957, 79, 2615–2617.
rotations of these isomers (1 and 21) were much different
25
D
(trichostatin D (1): ½aꢁ þ 225 (c 0.53, MeOH), 6-
26
epi-trichostatin D (21): ½aꢁ þ 46 (c 0.43, MeOH),
D
although NMR spectra of these isomers were
superimposed.13
In conclusion, we have achieved the stereoselective
synthesis of (+)-trichostatic acid, trichostatin D and 6-
epi-trichostatin D by our original methodologies includ-
ing remote stereoinduction with vinylketene silyl N,O-
acetal, direct reduction of a,b-unsaturated imide to
a,b-unsaturated aldehyde, and direct glycosylation of
D-glucose with N-hydroxyimide using Mitsunobu
conditions.
11. The spectra including 1H NMR, 13C NMR, IR of
synthetic trichostatin D were identical with those of the
natural product kindly supplied by Prof. Yoichi Haya-
kawa (Tokyo University of Science).
12. We also examined this transformation with the 20,30,40-
tris(trimethylsiloxy) analogue of 19 to avoid epimerization
at C-6 position during de-protection. Removal of silyl
groups proceeded under milder conditions (HF–pyridine:
pyridine = 1:6 in CH2Cl2, rt, 30min), but the product was
isolated in lower yield (21% in 2 steps) with lower [a]D
25
Acknowledgements
value (½aꢁD ¼ þ210, c 0.19, MeOH).
27
13. Selected data; 9b: ½aꢁ þ 100 (c 1.02, CHCl3). 1H NMR
We thank Professor Yoichi Hayakawa for the supply of
spectrum of trichostatin D. We are grateful to Takeda
Science Foundation and Sankyo Co. Ltd for generous
support of our program. The present work was also sup-
ported by 21 COE ꢀCenter for Practical Nano-Chemis-
tryꢁ, Consolidated Research Institute for Advanced
Science and Medical Care, and Grant-in-Aid from the
Ministry of Education, Science, Sports and Culture.
(600MHz, CDCl3): d D0.79 (3H, d, J = 7.0Hz), 0.94 (3H, d,
J = 7.0Hz), 0.95 (3H, d, J = 7.0Hz), 2.00 (3H, d,
J = 1.5Hz), 2.35 (1H, qqd, J = 7.0, 7.0, and 4.5Hz), 2.77
(1H, ddq, J = 10.0, 9.0, and 7.0Hz), 3.81 (1H, d,
J = 2.0Hz), 4.21 (1H, dd, J = 9.0 and 6.0Hz), 4.28 (1H,
dd, J = 9.0 and 2.0Hz), 4.36 (1H, dd, J = 9.0 and 9.0Hz),
4.60 (1H, ddd, 9.0, 6.0, and 4.5Hz), 5.84 (1H, dq,
J = 10.0 and 1.5Hz), 7.26 (2H, d, J = 8.5Hz), 7.47 (2H,
27
d, J = 8.5Hz). 19: ½aꢁD þ 56 (c 0.49, CHCl3). 1H NMR
(600MHz, CDCl3): d 0.06 (6H, s, –SiMe · 2), 0.07 (6H, s,
–SiMe · 2), 0.08 (3H, s, –SiMe), 0.09 (3H, s, –SiMe), 0.10
(3H, s, –SiMe), 0.88 (18H, s, t-Bu · 2), 0.90 (18H, s, t-
Bu · 2), 3.65 (1H, ddd, J = 8.5, 2.0, and 1.0Hz, H-4), 3.68
(1H, dd, J = 11.0 and 6.0Hz, H-6), 3.77 (1H, dd, J = 4.5
and 2.0Hz, H-3), 3.84 (1H, dd, J = 11.0 and 2.5Hz, H-6),
3.89 (1H, ddd, J = 4.5, 3.5, and 1.0Hz, H-2), 3.95 (1H,
ddd, J = 8.5, 6.0, and 2.5Hz, H-5), 4.87 (1H, d, J = 3.5Hz,
H-1), 5.39–5.51 (2H, br s, –NH2). (+)-Trichostatic acid (2):
References and notes
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Seto, H. J. Antibiot. 2000, 53, 179–183.
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26
1
½aꢁD þ 154 (c 0.32, MeOH). H NMR (600MHz, CDCl3):
d 1.32 (3H, d, J = 7.0Hz), 1.93 (3H, d, J = 1.0Hz), 3.06
(6H, s), 4.40 (1H, dq, J = 9.5 and 7.0Hz), 5.83 (1H, d,
J = 16.0Hz), 6.09 (1H, br d, J = 9.5Hz), 6.65 (2H, d,
J = 9.0Hz), 7.38 (1H, d, J = 16.0Hz), 7.85 (2H, d,
J = 9.0Hz). 13C NMR (150MHz, CDCl3): d 12.5, 17.7,
30.9, 40.0, 40.8, 110.7, 115.8, 123.8, 130.6, 132.6, 142.9,
151.3, 153.5, 171.8, 198.3, 207.0. Trichostatin D (1):
25
1
½aꢁD þ 225 (c 0.53, MeOH). H NMR (600MHz, DMSO-
d6, 75ꢁC): d 1.20 (3H, d, J = 6.0Hz, 6-Me), 1.86 (3H, s, 4-
Me), 3.00 (6H, s, –NMe2), 3.20 (1H, ddd, J = 9.0, 9.0, and
4.0Hz, H-40), 3.31 (1H, dd, J = 9.0 and 3.0Hz, H-20), 3.46
(1H, br dd, J = 9.0 and 9.0Hz, H-30), 3.54 (1H, ddd,
J = 12.0, 5.0, and 5.0Hz, H-60), 3.61 (1H, br d,
J = 12.0Hz, H-60), 3.71 (1H, m, H-50), 4.04 (1H, br,
–OH), 4.44 (1H, dq, J = 9.0 and 6.0Hz, H-6), 4.58 (1H, br,
–OH), 4.65 (1H, d, J = 4.0Hz, –OH), 4.80 (1H, br, –OH),
4.91 (1H, d, J = 3.0Hz, H-10), 5.84 (1H, d, J = 16.0Hz,
4. Morioka, H.; Ishihara, M.; Takezawa, M.; Hirayama, K.;
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44, 6013–6020.