4980
M. Kim, D. F. Wiemer / Tetrahedron Letters 45 (2004) 4977–4980
NHBOC
O
R
HN
O
Cl
O
NHNH2
NH
O
a
b or c
67%
O
O
O
9
10
11 R = CH3 (98%)
12 R = CH2OCH2C6H5 (94%)
Scheme 4. Reagents and conditions: (a) NH2NH2ÆH2O, Pyr, reflux, 3 h; (b) Boc-L-alanine, EDC, HOBt, NMM, THF; (c) Boc-O-benzyl-L-serine,
EDC, HOBt, NMM, THF.
2. Sleat, D. E.; Donnelly, R. J.; Lackland, H.; Liu, C.-G.;
Sohar, I.; Pullarkat, R. K.; Lobel, P. Science 1997, 277,
1802–1805.
3. Vines, D. J.; Warburton, M. J. FEBS Lett. 1999, 443, 131–
135.
NHBOC
O
N
NH
OBn
N
N
b
a
4. Kim, M. K.; Mao, Q.; Davidson, B. L.; Wiemer, D. F.
J. Med. Chem. 2003, 46, 1603–1608.
9
68%
99%
5. Dikov, A.; Dimitrova, M.; Ivanov, I.; Krieg, R.; Halbh-
uber, K.-J. J. Cell. Mol. Biol. 2000, 46, 1219–1225.
6. Mohlau, R. Chem. Ber. 1912, 45, 2233–2247.
7. Bradley, W.; Geddes, K. W. J. Chem. Soc. 1952, 1630–
1636.
O
13
O
14
Scheme 5. Reagents and conditions: (a) NH2NH2ÆH2O, Pyr, reflux,
9 h; (b) Boc-O-benzyl- -serine, EDC, HOBt, NMM, THF.
8. Showalter, H. D. H.; Johnson, J. L.; Hoftiezer, J. M.
J. Heterocyclic Chem. 1986, 23, 1491–1501.
L
9. Krapcho, A. P.; Avery, K. L., Jr. J. Org. Chem. 1988, 53,
5927–5929.
10. Zhang, L. H.; Meier, W. E.; Watson, E. J.; Gibson, E. P.
Tetrahedron Lett. 1994, 35, 3675–3678.
11. Goodman, M.; Kenner, G. W. In Advances in Protein
Chemistry; Academic: New York, 1957; Vol. 12, pp 488–
638.
12. Sheehan, J. C.; Cruickshank, P. A.; Boshart, G. L. J. Org.
Chem. 1961, 26, 2525–2528.
13. Xu, Y.; Miller, M. J. J. Org. Chem. 1998, 63, 4314–4322.
14. For compound 5: 1H NMR (CDCl3) d 8.39 (d, J ¼ 8:1 Hz,
1H), 8.24 (dd, J ¼ 6:6, 2.2 Hz, 1H), 8.04 (d, J ¼ 7:3 Hz,
1H), 7.77 (t, J ¼ 7:8 Hz, 1H), 7.64–7.57 (m, 2H), 5.76–5.66
(m, 1H), 5.44 (d, J ¼ 8:1 Hz, 1H), 1.65 (d, J ¼ 6:9 Hz, 3H),
1.49 (s, 9H); 13C NMR (CDCl3) d 181.1, 173.6, 155.1,
144.1, 137.9, 137.3, 135.0, 133.2, 132.2, 131.6, 129.6, 126.4,
124.6, 123.6, 123.1, 120.7, 80.1, 49.2, 28.2 (3C), 19.2;
HRMS (FAB) calcd for C22H21N3O4Cl (M+H)þ 426.1221,
found 426.1226.
Figure 2. (A) Key HMQC ( ) and HMBC ( ) correlations and (B)
NOESY correlations for compound 14.
the structures of the condensation products and will
advance their use as probes of TPP-1 distribution fol-
lowing gene-transfer experiments.
15. Oliva, A.; Ellis, M.; Fiocchi, L.; Menta, E.; Krapcho, A. P.
J. Heterocyclic Chem. 2000, 37, 47–55.
16. For compound 11: 1H NMR (CDCl3) d 10.54 (s, 1H,
exchanges with D2O), 8.31–8.21 (m, 3H), 7.78–7.71 (m,
3H), 7.42–7.30 (m, 5H), 7.23 (d, J ¼ 8:5 Hz, 1H), 5.46
(d, J ¼ 6:7 Hz, 1H), 4.64 (d, J ¼ 11:7 Hz, 1H), 4.59
(d, J ¼ 11:7 Hz, 1H), 4.51–4.48 (m, 1H), 4.00 (dd,
J ¼ 8:8, 3.6 Hz, 1H), 3.70 (dd, J ¼ 9:0, 6.4 Hz, 1H), 1.49
(s, 9H); 13C NMR (CDCl3) d 185.3, 182.9, 170.4, 155.5,
151.0, 137.1, 135.1, 134.1, 134.0, 133.8, 133.3, 132.6, 128.5
(2C), 128.0, 127.9 (2C), 126.8, 126.6, 118.4, 118.0, 114.4,
80.7, 73.7, 69.7, 53.4, 28.3 (3C); HRMS (FAB) calcd for
C29H30N3O6 (M+H)þ 516.2135, found 516.2129.
Acknowledgements
Financial support from the Batten Disease Support and
Research Association is gratefully acknowledged.
References and notes
1. Bennett, M. J.; Hofmann, S. L. J. Inherit. Metab. Dis.
1999, 22, 535.