5866
M. Oikawa et al. / Tetrahedron Letters 46 (2005) 5863–5866
Takeda, Y.; Sasaki, M. Tetrahedron Lett. 2005, 46,
Br
4667–4670.
7. Oikawa, M.; Ikoma, M.; Sasaki, M. Tetrahedron Lett.
2005, 46, 415–418.
8. Paulvannan, K. Tetrahedron Lett. 1999, 40, 1851–1854;
Paulvannan, K. J. Org. Chem. 2004, 69, 1207–1214.
9. Lee, D. S.; Sello, J. K.; Schreiber, S. L. Org. Lett. 2000, 2,
709–712.
10. Prepared from p-bromoaniline by two-step reactions
including formylation (HCOOH, Ac2O, pyridine, THF,
0 °C!rt) and dehydration (POCl3, Et3N, CH2Cl2, 0 °C) in
81% yield; Obrecht, R.; Herrmann, R.; Ugi, I. Synthesis
1985, 400–402.
O
O
H
N
N
O
H
H
O
H
N
Br
scaffold L
11. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
1999, 1, 953–956.
1
12. Selected spectroscopic data for (E)-isomer of 4: H NMR
(300 MHz, CDCl3) d 7.34–6.97 (m, 12H), 6.91 (d, 2H,
J = 6.9 Hz), 6.60 (d, 1H, J = 15.6 Hz), 6.22 (d, 1H,
J = 15.6 Hz), 6.18 (m, 1H), 6.08 (d, 1H, J = 11.1 Hz),
5.67 (br t, 1H, J = 5.4 Hz), 5.25 (d, 1H, J = 15.0 Hz), 4.76
(dd, 1H, J = 2.4, 4.5 Hz), 4.46 (dd, 1H, J = 5.4, 10.5 Hz),
4.36 (dd, 1H, J = 6.0, 8.4 Hz), 4.26 (dd, 1H, J = 6.0,
8.4 Hz), 4.02 (d, 1H, J = 6.6 Hz), 3.75 (s, 1H), 3.63 (q, 1H,
J = 8.4 Hz); 13C NMR (150 MHz, CDCl3) d 174.3, 167.6,
167.3, 142.1, 136.8, 136.4, 135.3, 132.3, 132.0, 130.8, 128.9,
128.7, 128.5, 128.4, 128.0, 127.9, 127.7, 127.7, 127.6, 127.4,
127.4, 126.8, 119.9, 85.1, 77.1, 71.8, 54.9, 50.5, 46.4, 45.8,
44.0; FAB-HR-MS calcd for C39H35O4N3Br (M+H+) m/z
688.1733, found 688.1818.
HN
H
N
O
O
R
H
H
O
H
NH
O
R
scaffold M
Figure 2. Other skeletons potentially included in our DOS approach.
13. The E/Z selectivity at the newly formed double bond of
the acyclic moiety was determined from 1H NMR spectra;
4 (>10:1), 5 (6:4), 6 (6:4), 8 (>10:1), 9 (7:3), and 10 (6:4).
We have found that the double bond can be selectively
hydrogenated quantitatively (H2, Pd/C, MeOH, rt).
14. The low isolated yields in these reactions are supposed to
be due to the crowdness of the skeleton. Though nearly
quantitative amount of the unreacted 7 can be recovered
intact, we are currently studying the reaction conditions to
improve the yields.
References and notes
1. Schreiber, S. L. Bioorg. Med. Chem. 1998, 6, 1127–1152;
Crews, C. M.; Splittgerber, U. Trends Biochem. Sci. 1999,
24, 317–320; Stockwell, B. R. Nat. Rev. Genet. 2000, 1,
116–125; Mootz, H. D.; Muir, T. W. J. Am. Chem. Soc.
2002, 124, 9044–9045; Chen, J. Chem. Biol. 2002, 9, 543–
544; Schreiber, S. L. Chem. Eng. News 2003, 81, 51–
61.
2. Schreiber, S. L. Science 2000, 287, 1964–1969.
3. Burke, M. D.; Schreiber, S. L. Angew. Chem., Int. Ed.
2004, 43, 46–58.
1
15. Selected spectroscopic data for (E)-isomer of 8: H NMR
(300 MHz, CDCl3) d 7.34–6.98 (m, 19H), 6.11 (m, 1H),
5.82 (br t, 1H, J = 5.8 Hz), 5.79 (m, 1H), 5.46 (d, 1H,
J = 15.0 Hz), 5.27 (d, 1H, J = 14.1 Hz), 5.17 (d, 2H,
J = 10.5 Hz), 4.47 (t, 1H, J = 7.5 Hz), 4.34 (d, 2H,
J = 5.1 Hz), 4.10 (s, 1H), 3.89 (d, 1H, J = 14.1 Hz), 3.60
(s, 1H), 3.32 (d, 1H, J = 6.9 Hz); 13C NMR (125 MHz,
CDCl3) d 174.6, 171.1, 167.0, 139.8, 137.7, 136.8, 135.3,
134.2, 132.9, 132.4, 131.7, 128.9, 128.7, 128.6, 128.5, 128.0,
127.8, 127.6, 127.5, 126.8, 122.2, 119.2, 119.0, 87.8, 83.3,
66.9, 55.9, 53.6, 52.9, 45.6, 43.7; ESI-MS calcd for
C39H35O4N3Br (M+H+) m/z 688.1733, found 688.1805.
4. Sello, J. K.; Andreana, P. R.; Lee, D. S.; Schreiber, S. L.
Org. Lett. 2003, 5, 4125–4127.
5. Burke, M. D.; Berger, E. M.; Schreiber, S. L. Science 2003,
302, 613–618; Burke, M. D.; Berger, E. M.; Schreiber, S.
L. J. Am. Chem. Soc. 2004, 126, 14095–14104.
6. For our recent efforts in this field, see; Oikawa, M.;
Tanaka, T.; Kusumoto, S.; Sasaki, M. Tetrahedron Lett.
2004, 45, 787–790; Oikawa, M.; Ikoma, M.; Sasaki, M.
Tetrahedron Lett. 2004, 45, 2371–2375; Oikawa, M.;