S. Kehraus, A. Krick, G. Kelter, A. Maier, H. H. Fiebig, A. D. Wright
and G. M. König, J. Nat. Prod., 2008, 71, 309–312.
CH2Cl2 was added boron tribromide (1 M in CH2Cl2, 0.14 mL).
The reaction mixture was stirred at −15 °C for 5 h, quenched
with a saturated solution of NaHCO3, and extracted with
CH2Cl2. The organic extracts were washed with water (2×),
dried over Na2SO4, and concentrated to dryness under reduced
pressure. The residue was redissolved in methanol, washed with
hexane and the methanol was removed in vacuo. This compound
could not be fully characterized and all attempts at purification
were unsuccessful. The compound was used in the next step
without further purification.
8 (a) S. Aoki, S. H. Cho, A. Hiramatsu, N. Kotoku and M. Kobayashi,
J. Nat. Med., 2006, 60, 231–235; (b) S. Aoki, S. H. Cho, M. Ono,
T. Kuwano, S. Nakao, M. Kuwano, S. Nakagawa, J. Q. Gao, T. Mayumi,
M. Shibuya and M. Kobayashi, Anti-Cancer Drugs, 2006, 17, 269–278.
9 M. Jaspars, T. Rali, M. Laney, R. C. Schatzman, M. C. Diaz,
F. J. Schmitz, E. O. Pordesimo and P. Crews, Tetrahedron, 1994, 50,
7367–7374.
10 E. N. Segraves, R. R. Shah, N. L. Segraves, T. A. Johnson, S. Whitman,
J. K. Sui, V. A. Kenyon, R. H. Cichewicz, P. Crews and T. R. Holman,
J. Med. Chem., 2004, 47, 4060–4065.
11 (a) M. M. Mack, T. F. Molinski, E. D. Buck and I. N. Pessah, J. Biol.
Chem., 1994, 269, 23236–23249; (b) M. A. Franklin, S. G. Penn,
C. B. Lebrilla, T. H. Lam, I. N. Pessah and T. F. Molinski, J. Nat. Prod.,
1996, 59, 1121–1127; (c) T. Yang, E. Esteve, I. N. Pessah, T. F. Molinski,
P. D. Allen and J. R. López, Am. J. Physiol. - Cell Physiol., 2007, 292,
C1591–C1598.
12 J. García, G. Franci, R. Pereira, R. Benedetti, A. Nebbioso, F. Rodríguez-
Barrios, H. Gronemeyer, L. Altucci and A. R. de Lera, Bioorg. Med.
Chem., 2011, 19, 3637–3649.
13 D. A. Whiting, Oxidative coupling of phenols and phenol ethers, in Com-
prehensive Organic Synthesis, ed. B. M. Trost, I. Fleming and G. Patten-
den, Pergamon, Oxford, 1991, vol. 3, pp. 659–703.
14 S. R. Taylor, A. T. Ung, S. G. Pyne, B. W. Skelton and A. H. White,
Tetrahedron, 2007, 63, 11377–11385.
15 (a) Z. W. Guo, K. Machiya, G. M. Salamonczyk and C. J. Sih, J. Org.
Chem., 1998, 63, 4269–4276; (b) S. Nishiyama and S. Yamamura, Tetra-
hedron Lett., 1982, 23, 1281–1284.
Dioxepine bastadin 3 (3). A solution of MeReO3 (0.17 mg,
0.007 mmol) in 30% H2O2 (9 μL) and absolute EtOH (9 μL)
was added to a stirred solution of diamine 21 (9 mg,
0.009 mmol) in absolute EtOH (43 μL). The resulting solution
was stirred for an additional 5 h at room temperature, and then
the reaction was diluted with CH2Cl2 and washed with H2O. The
organic layer was dried over Na2SO4, and filtered, and then the
solvent was removed. The residue was purified by column
chromatography on silica gel (99 : 1 CH2Cl2–MeOH) to afford
3.5 mg (26% in two steps) of dioxepine bastadin 3 as a white
solid. The spectroscopic data matched those described for the
natural product (see ESI†).
16 A. G. Brown and P. D. Edwards, Tetrahedron Lett., 1990, 31, 6581–6584.
17 M. A. Schwartz, B. F. Rose, R. A. Holton, S. W. Scott and
B. Vishnuvajjala, J. Am. Chem. Soc., 1977, 99, 2571–2578.
18 (a) F. E. Kühn, A. Scherbaum and W. A. Herrmann, J. Organomet.
Chem., 2004, 689, 4149–4164; (b) T. R. Boehlow, J. J. Harburn and
C. D. Spilling, J. Org. Chem., 2001, 66, 3111–3118.
19 E. Mume, A. Orlova, B. Larsson, A.-S. Nilsson, F. Y. Nilsson, S. Sjöberg
and V. Tolmachev, Bioconjugate Chem., 2005, 16, 1547–1555.
20 O. Hoshino, M. Murakata and K. Yamada, Bioorg. Med. Chem. Lett.,
1992, 2, 1561–1562.
Acknowledgements
This work was supported by the European Union
(LSHC-CT-2005-518417 ‘Epitron’), Ministerio de Economía y
Competitividad-Spain (SAF2010-17935-FEDER) and Xunta de
Galicia (Grant 08CSA052383PR from DXI+D+i; Consolidación
2006/15 from DXPCTSUG; Inbiomed).
21 (a) Among the reaction conditions that provided dinitrile 15, we used (i)
i
EDCI and HOBt, CH2Cl2, Pr2NEt, 14, 0 °C, 18 h; (ii) HOBt, DCC,15a
DMF; then 14, Et3N, 25 °C, 18 h,15a HATU;22 (iii) CH2Cl2, DMF,
(COCl)2 (20 equiv.); then 14, Et3N, 25 °C, 3 h; (b) Among the reaction
conditions that resulted in decomposition, we used (i) NHPI, DCC,
dioxane; then 14, Et3N, 25 °C, 18 h; (ii) HOBt, DIC,12,20 DMF, 14, Et3N,
60 °C, 15 h or microwaves; (iii) HATU,22b Et3N, 14, 25 °C, 18 h; (iv)
COMU, TMP,24 14, 25 °C, 18 h; (v) PyBOP, DMF, DMAP, 14, 0 to
25 °C, 16 h; (vi) T3P, N-methylmorpholine,23 DMF, 14, 25 °C, 18 h;
(vii) 2-bromophenylboronic acid (0.01 equiv.),24 4 Å MS, CH2Cl2–
DMF(1 : 1 v/v), 14, 25 °C, 48 h.
References
1 A. W. W. Van Wyk, K. M. Zuck and T. C. McKee, J. Nat. Prod., 2011,
74, 1275–1280.
2 (a) R. Kazlauskas, R. O. Lidgard, P. T. Murphy and R. J. Wells, Tetrahe-
dron Lett., 1980, 21, 2277–2280; (b) R. Kazlauskas, R. O. Lidgard and
P. T. Murphy, Aust. J. Chem., 1981, 34, 765–786; (c) S. Nishiyama,
T. Suzuki and S. Yamamura, Tetrahedron Lett., 1982, 23, 3699–3702;
(d) S. Miao, R. J. Andersen and T. M. Allen, J. Nat. Prod., 1990, 53,
1441–1446; (e) E. O. Pordesimo and F. J. Schmitz, J. Org. Chem., 1990,
55, 4704–4709; (f) A. F. Dexter, M. J. Garson and M. E. Hemling,
J. Nat. Prod., 1993, 56, 782–786; (g) S. K. Park, J. Jurek, J. R. Carney
and P. J. Scheuer, J. Nat. Prod., 1994, 57, 407–410; (h) J. C. Coll,
P. S. Kearns, J. A. Rideout and V. Sankar, J. Nat. Prod., 2002, 65, 753–
756; (i) L. Calcul, W. D. Inman, A. A. Morris, K. Tenney, J. Ratnam,
J. H. McKerrow, F. A. Valeriote and P. Crews, J. Nat. Prod., 2010, 73,
365–372; ( j) A. R. Carroll, S. M. Kaiser, R. A. Davis, R. W. Moni,
J. N. A. Hooper and R. J. Quinn, J. Nat. Prod., 2010, 73, 1173–1176.
3 (a) J. R. Carney, P. J. Scheuer and M. Kelly-Borges, J. Nat. Prod., 1993,
56, 153–157; (b) Y. Venkateswarlu, U. Venkatesham and M. Rama Rao,
J. Nat. Prod., 1999, 62, 893–894.
4 A. V. Reddy, K. Ravinder, M. Narasimhulu, A. Sridevi,
N. Satyanarayana, A. K. Kondapi and Y. Venkateswarlu, Bioorg. Med.
Chem., 2006, 14, 4452–4457.
5 J. Peng, J. Li and M. T. Hamann, The marine bromotyrosine derivatives,
in The Alkaloids: Chemistry and Biology, ed. G. A. Cordell, 2005,
vol. 61, pp. 59–262.
6 G. R. Pettit, M. S. Butler, M. D. Williams, M. J. Filiatrault and
R. K. Pettit, J. Nat. Prod., 1996, 59, 927–934.
7 (a) G. R. Pettit, M. S. Butler, C. G. Bass, D. L. Doubek, M. D. Williams,
J. M. Schmidt, R. K. Pettit, J. N. A. Hooper, L. P. Tackett and
M. J. Filiatrault, J. Nat. Prod., 1995, 58, 680–688; (b) H. Greve,
22 (a) A. C. Louis, I. Hideko, E.-F. Ayman, J. F. Fernando, Z. Chongwu,
L. Yunsub, M. F. Bruce, H. Peter, H. Christiane, M. Clemens, W. Holger,
K. Jana, B. Michael and B. Michael, Angew. Chem., Int. Ed., 2002, 41,
441–445; (b) Y. Nishiyama, S. Ishizuka and K. Kurita, Tetrahedron Lett.,
2001, 42, 8789–8791.
23 H. Wissmann and H.-J. Kleiner, Angew. Chem., Int. Ed., 1980, 19, 133–
134.
24 R. M. Al-Zoubi, O. Marion and D. G. Hall, Angew. Chem., Int. Ed.,
2008, 47, 2876–2879.
25 (a) E. A. Couladouros, E. N. Pitsinos, V. I. Moutsos and G. Sarakinos,
Chem.–Eur. J., 2005, 11, 406–421; (b) N. Kotoku, H. Tsujita,
A. Hiramatsu, C. Mori, N. Koizumi and M. Kobayashi, Tetrahedron,
2005, 61, 7211–7218.
26 A. Minatti and K. H. Dötz, Tetrahedron: Asymmetry, 2005, 16, 3256–
3267.
27 B. J. Morgan, C. A. Mulrooney and M. C. Kozlowski, J. Org. Chem.,
2009, 75, 44–56.
28 (a) H. Yoshino, M. Tsujii, M. Kodama, K. Komeda, N. Niikawa,
T. Tanase, N. Asakawa, K. Nose and K. Yamatsu, Chem. Pharm. Bull.,
1990, 38, 1735–1737; (b) H. Yoshino, Y. Tsuchiya, I. Saito and M. Tsujii,
Chem. Pharm. Bull., 1987, 8, 3438–3441.
29 For a recent review on the synthesis of oximinotyrosine-derived marine
natural products, see: F. Hentschel and T. Lindel, Synthesis, 2010, 181–
204.
6950 | Org. Biomol. Chem., 2012, 10, 6945–6950
This journal is © The Royal Society of Chemistry 2012