D. Hernaꢀndez et al. / Tetrahedron 63 (2007) 9862–9870
9869
128.4 (2d); 128.9 (2d); 130.5 (d); 138.0 (d); 141.8 (d); 141.9
(d). MS (MALDI): m/z 782.19 (M, 40).
and the Barcelona Science Park. We gratefully acknowledge
PharmaMar S.L. for performing the preliminary biological
tests. D.H. thanks the Ministerio de Educacioꢀn y Ciencia
for a doctoral fellowship, and E.R. thanks the Principado
de Asturias for a postdoctoral fellowship.
5.2.12. Peptide 12b. Peptide 12a (9 mg, 0.0114 mmol) was
deprotected with 95% TFA (1 mL). The crude was dissolved
in dry THF (1 mL), and the solution was cooled to 0 ꢀC, TEA
(15.82 mL, 0.114 mmol) and MsCl (4.4 mL, 0.057 mmol)
were added dropwise. The resulting solution was stirred for
2 h at 0 ꢀC, then washed with NH4Cl and water, dried, and
concentrated. The solvents were removed and the residue
was washed with MeCN to give a white solid (7.4 mg,
90%), mp (MeCN) 147–149 ꢀC. [a]D +12.4 (c 0.15,
CHCl3). 1H NMR (CDCl3, 500 MHz) d 0.79–0.92 (m,
12H); 0.99–1.09 (m, 2H); 1.41–1.45 (m, 1H); 1.52–1.55
(m, 1H); 3.65–3.75 (m, 2H); 3.78–3.89 (m, 1H); 6.06 (s,
1H); 6.70 (s, 1H); 7.43–7.52 (m, 4H); 7.96 (s, 1H); 8.20 (s,
1H); 8.27 (s, 1H); 8.30 (s, 1H); 8.31 (br s, 1H); 8.36–8.37
(m, 2H); 8.47 (br s, 1H). 13C NMR (CDCl3, 125 MHz)
d 11.29 (q); 13.9 (q); 15.2 (q); 18.7 (q); 25.2 (t); 30.2 (d);
30.7 (d); 53.6 (d); 63.2 (d); 111.7 (t); 119.5 (d); 127.9 (d);
128.4 (2d); 130.2 (2d); 137.7 (d); 139.0 (d); 139.4 (d). MS
(MALDI): m/z 749.3 (M+Na, 100), 765.3 (M+K, 47).
References and notes
1. Recent revisions about the chemistry and properties can be
found in: (a) Roy, R. S.; Gehring, A. M.; Milne, J. C.;
Belshaw, P. J.; Walsh, C. T. Nat. Prod. Rep. 1999, 16, 249; (b)
Yeh, V. S. C. Tetrahedron 2004, 60, 11995; (c) Riego, E.;
ꢀ
ꢀ
Hernandez, D.; Albericio, F.; Alvarez, M. Synthesis 2005, 1907.
2. Roesener, J. A.; Scheuer, P. J. J. Am. Chem. Soc. 1986, 108,
846; For absolute stereochemistry of ulapualide A, see:
Allingham, J. S.; Tanaka, J.; Marriott, G.; Rayment, I. Org.
Lett. 2004, 6, 597.
3. Matsunaga, S.; Fusetani, N.; Hashimoto, K.; Koseki, K.; Noma,
M.; Noguchi, H.; Sankawa, U. J. Org. Chem. 1989, 54, 1360.
4. (a) Fusetani, N.; Yasumuro, K.; Matsunaga, S.; Hashimoto, K.
Tetrahedron Lett. 1989, 30, 2809; (b) Rashid, M. A.; Gustafson,
K. R.; Cardeilina, J. H., II; Boyd, M. R. J. Nat. Prod. 1995, 58,
1120; (c) Matsunaga, S.; Nogata, Y.; Fusetani, N. J. Nat. Prod.
1998, 61, 663; (d) Matsunaga, S.; Sugawara, T.; Fusetani, N.
J. Nat. Prod. 1998, 61, 1164; (e) Phuwapraisirisan, P.;
Matsunaga, S.; van Soest, R. W. M.; Fusetani, N. J. Nat.
Prod. 2002, 65, 942.
5. Kobayashi, J.; Tsuda, M.; Fuse, H.; Sasaki, T.; Mikami, Y.
J. Nat. Prod. 1997, 60, 150.
6. Kobayashi, J.; Murata, O.; Shigemori, H.; Sasaki, T. J. Nat.
Prod. 1993, 56, 787.
7. Michael, J. P.; Pattenden, G. Angew. Chem., Int. Ed. Engl. 1993,
32, 1.
8. (a) Shin-ya, K.; Wierzba, K.; Matsuo, K.; Ohtani, T.; Yamada, Y.;
Furihata, K.; Hayakawa, Y.; Seto, H. J. Am. Chem. Soc. 2001,
123, 1262; (b) Kim, M.-Y.; Vankayalapati, H.; Shin-ya, K.;
Wierza, K.; Hurley, L. H. J. Am. Chem. Soc. 2002, 124, 2098.
9. Hayata, A.; Takebashi, Y.; Nagai, K.; Hiramoto, M. Jpn. Kokai
TokkyoKohoJP11180997-A, 1999;Chem. Abstr. 1999, 131,101.
10. Romero, F.; Malet, L.; Can˜edo, M. L.; Cuevas, C.; Reyes, F.
WO 2005/000880 A2, 2005.
11. Same structure was proposed for Merchercharmycin A isolated
from a marine-derived Thermoactinomices sp. by Kanoh, K.;
Matsuo, Y.; Adachi, K.; Imagawa, H.; Nishizawa, M.;
Shizuri, Y. J. Antibiot. 2005, 58, 289.
5.2.13. Peptide 13. A solution of carboxylic acid (150 mg,
0.166 mmol) obtained from 1 in dry THF–DMF (10 and
2 mL) was cooled to 0 ꢀC. EDC$HCl (0.22 mg, 1.16 mmol),
DIEA (0.19 mL, 1.16 mmol), and Pfp-OH (0.229 mg,
1.24 mmol) were then added, and the reaction mixture was
stirred at room temperature for 20 h. The solvents were re-
moved in vacuo, and the residue was diluted with CH2Cl2,
and then washed with 5% aqueous NaHCO3 and aqueous
NH4Cl. The organic solution was dried and concentrated,
and the residue was diluted in TFA–CH2Cl2 (1 and 3 mL).
The solution was stirred for 1 h at room temperature, and
then the TFAwas removed. The crude material was dissolved
in THF (300 mL). DIEA (0.28 mL, 1.66 mmol) and CuSO4
(132 mg, 0.83 mmol) were added, and the mixture was
stirred for 72 h at room temperature. The solvents were re-
moved, and the crude was purified by silica gel chromato-
graphy (9:1 CH2Cl2–MeOH) to give 13 (58.8 mg, 37%) as
a yellow solid, mp (MeCN) 140–142 ꢀC. [a]D +7.7 (c 0.39,
CHCl3). 1H NMR (CDCl3, 400 MHz) d 0.94–1.09 (m,
12H); 1.13 (s, 9H); 1.20–1.32 (m, 1H); 1.51–1.61 (m, 1H);
2.08–2.26 (m, 1H); 2.32–2.43 (m, 1H); 3.77–3.83 (m, 1H);
3.96–4.01(m, 1H);4.55–4.65(m, 1H); 4.82–4.91 (m, 1H); 5.38–
5.45(m, 1H);6.67(d, J¼8.4 Hz, 1H); 6.81 (d, J¼8.4 Hz, 1H);
7.42–7.47 (m, 3H); 8.24 (s, 1H); 8.29–8.30 (m, 2H); 8.31 (s,
1H); 8.40 (s, 1H); 8.47 (s, 1H). 13C NMR (CDCl3, 100 MHz)
d 11.4 (q); 14.7 (q); 17.6 (q); 18.9 (q); 26.2 (t); 27.3 (q); 30.9
(d); 36.4 (d); 48.9 (d); 57.2 (d); 57.5 (d); 61.8 (t); 74.3 (s);
122.3 (d); 125.1 (s); 126.4 (s); 126.5 (s); 128.3 (2d); 128.5
(2d); 128.7 (s); 129.4 (s); 130.1 (s); 130.3 (d); 130.9 (s);
131.5 (s); 136.3 (s); 136.4 (d); 139.3 (d); 139.8 (d); 143.3
(s); 151.8 (s); 153.2 (s); 155.1 (s); 156.8 (s); 157.2 (s);
158.2 (s); 161.0 (s); 161.5 (s); 162.0 (s); 167.7 (s); 171.5
(s). 19F NMR (CDCl3, 400 MHz) d 84.0 (s). MS (MALDI):
m/z 1006.7 (M+K, 100).
ꢀ
ꢀ
ꢀ
12. Can˜edo, M. L.; Martınez, M.; Sanchez, J. M.; Fernandez-
ꢀ
ꢀ
Puentes J. L.; Malet, L.; Perez J.; Romero, F.; Garcıa, L. F.
Fourth Eur. Conference on Marine Natural Products, Paris,
2005; poster 54.
13. Deeley, J.; Pattenden, G. Chem. Commun. 2005, 797.
14. Doi, T.; Yoshida, M.; Shin-ya, K.; Takahashi, T. Org. Lett.
2006, 8, 4165. A penta-azole related to telomestatin has been
recently described by Marson, M. C.; Saadi, M. Org. Biomol.
Chem. 2006, 4, 3892.
ꢀ
˜
15. Hernandez, D.; Vilar, G.; Riego, E.; Canedo, L. M.; Cuevas, C.;
ꢀ
Albericio, F.; Alvarez, M. Org. Lett. 2007, 9, 809.
ꢀ ꢀ
€ €
ꢀ
ꢀ
16. (a) Kaleta, Z.; Tarkanyi, G.; Gomory, A.; Kalman, F.; Nagy, T.;
Soos, T. Org. Lett. 2006, 8, 1093; (b) Sowinski, J. A.; Toogood,
ꢀ
Acknowledgements
P. L. J. Org. Chem. 1996, 61, 7671.
17. 7a was obtained as unique stereoisomer as indicated in its H
and C NMR maintaining the configuration of starting L-Ser
used in the preparation of 5a and 6a.
This study was partially supported by CICYT (BQU 2003-
00089 and BQU2006-03794), Generalitat de Catalunya,