4830
M. Sassatelli et al. / Tetrahedron Letters 45 (2004) 4827–4830
Table 1. Chemical yields for the synthesis of compounds 4–21
and concentrated under vacuum to give a residue, which
was purified by flash chromatography (eluent cyclohexane/
EtOAc 80:20). Compound 16 was obtained as red crystals
(mp ¼ 205 °C) with 40% yield.
Compounds
Yields (%)
4
95
66
80
74
88
65
78
82
64
62
49
66
40
40
25a
60
59
18a
5
11. Ward, D. E.; Gai, Y.; Kaller, B. F. J. Org. Chem. 1995, 60,
7830–7836.
6
7
12. Typical procedure for preparation of 19: BBr3 (1.5 mL,
1.5 mmol) was added to a cooled (ꢀ80 °C) solution of 16
(80 mg, 0.102 mmol) in CH2Cl2 (9.5 mL). The mixture was
stirred for 12 h before hydrolysis at ꢀ80 °C and warm up
to room temperature. After decantation and extraction
with EtOAc, the organic phases were dried over MgSO4,
and concentrated under vacuum to give a residue, which
was purified by chromatography (eluent EtOAc/MeOH
from 95:5 to 85:15). The glycosyl isoindigo 19 was
obtained as a red solid (mp >300 °C) in 60% yield.
8
9
10
11
12
13
14
15
16
17
18
19
20
21
13. Spectral data of 19: IR (KBr): mNH;OH: 3377 cmꢀ1; mC@O
:
1696, 1680 cmꢀ1; mC@C: 1604 cmꢀ1. HRMS (FABþ) calcd
1
for C22H21N2O7 [MþH]þ: 425.1349. Found: 425.1357. H
(400 MHz, DMSO-d6): 3.29–3.46 (m, 3H), 3.52–3.59 (m,
1H), 3.78–3.84 (m, 1H), 3.86–4.02 (br s, 1H); 4.68 (t,
J ¼ 5:5 Hz, 1H, OH), 5.18 (d, J ¼ 5:0 Hz, 1H, OH); 5.22
(d, J ¼ 5:0 Hz, 1H, OH), 5.40 (d, J ¼ 5:0 Hz, 1H, OH),
a Chemical yield not optimized.
0
0
5.36–5.44 (br s, 1H, H1 ), 6.92 (d, J ¼ 7:5 Hz, 1H, H7 ),
substituents what was not clearly established in the
synthetic pathway described in the patents.7;8 The bio-
logical properties of these compounds are currently
under investigation.
0
7.04 (t, J ¼ 8:0 Hz, 1H, H5 ), 7.13 (t, J ¼ 7:5 Hz, 1H, H5),
0
7.28 (d, J ¼ 8:0 Hz, 1H, H7), 7.42 (t, J ¼ 7:5 Hz, 1H, H6 ),
0
7.48 (t, J ¼ 7:5 Hz, 1H, H6), 9.05 (d, J ¼ 8:0 Hz, 1H, H4 ),
9.19 (d, J ¼ 7:5 Hz, 1H, H4), 11.0 (s, 1H, NH). 13C
(100 MHz, DMSO-d6): 61.0 (CH2), 68.4, 69.8, 77.3, 80.1,
0
81.9 (CHsugar), 109.7 (C7 ), 111.5 (C7), 121.2 (C5 ), 121.7
0
0
(C5), 128.8 (C4), 129.4 (C4 ), 132.3 (C6), 132.9 (C6 ), 121.1
0
References and notes
0
(C3a), 121.6 (C3 a), 132.1 (C3), 134.0 (C3 ), 142.3 (C7a),
0
0
144.3 (C7 a), 167.0, 168.7 (C@O).
1. Leclerc, S.; Garnier, M.; Hoessel, R.; Marko, D.; Bibb, J.
A.; Snyder, G. L.; Greengard, P.; Biernat, J.; Wu, Y.-Z.;
Mandelkow, E.-M.; Eisenbrand, G.; Meijer, L. J. Biol.
Chem. 2001, 276, 251–260.
2. Hoessel, R.; Leclerc, S.; Endicott, J. A.; Nobel, M. E. M.;
Lawrie, A.; Tunnah, P.; Leost, M.; Damiens, E.; Marie,
D.; Marko, D.; Niederberger, E.; Tang, W.; Eisenbrand,
G.; Meijer, L. Nat. Cell. Biol. 1999, 1, 60–67.
3. Messaoudi, S.; Sancelme, M.; Polard-Housset, V.; Aboab,
B.; Moreau, P.; Prudhomme, M. Eur. J. Med. Chem. 2004,
39, 453–458.
4. Laird, A. D.; Cherrington, J. M. Expert Opin. Investig.
Drugs 2003, 12, 51–64.
5. Sun, L.; Liang, C.; Shirazian, S.; Zhou, Y.; Miller, T.; Cui,
J.; Fukuda, J. Y.; Chu, J.-Y.; Nematalla, A.; Wang, X.;
Chen, H.; Sistla, A.; Luu, T. C.; Tang, F.; Wei, J.; Tang,
C. J. Med. Chem. 2003, 46, 1116–1119.
6. Moshinsky, D. J.; Bellamacina, C. R.; Boisvert, D. C.;
Huang, P.; Hui, T.; Jancarik, J.; Kim, S.-H.; Rice, A. G.
Biochem. Biophys. Res. Commun. 2003, 310, 1026–1031.
7. Wang, L.; Liu, X.; Chen, R. U.S. Patent 6,566,341, 2003;
Chem. Abstr. 2003, 138, 379213.
8. Wang, L.; Liu, X.; Chen, R. WO Patent, WO 03051900,
2003; Chem. Abstr. 2003, 139, 47135.
9. Papageorgiou, C.; Borer, X. Helv. Chim. Acta 1988, 71,
1079–1083.
14. Spectral data of 20 obtained as a red solid (mp >300 °C):
IR (KBr): mNH;OH: 3540, 3500–3200 cmꢀ1; mC@O: 1700,
1680 cmꢀ1; mC@C: 1620, 1600 cmꢀ1. H (400 MHz, DMSO-
1
d6): 3.27–3.45 (m, 3H), 3.49–3.58 (m, 1H), 3.78 (dd,
J1 ¼ 11:0 Hz, J2 ¼ 5:0 Hz, 1H), 3.79–3.96 (m, 1H); 4.66 (t,
J ¼ 5:5 Hz, 1H, OH), 5.17 (d, J ¼ 5:0 Hz, 1H, OH), 5.21
(d, J ¼ 4:0 Hz, 1H, OH), 5.34–5.39 (m, 1H), 5.40 (d,
J ¼ 5:0 Hz, 1H, OH), 6.91 (d, J ¼ 8:0 Hz, 1H), 7.03 (td,
J1 ¼ 8:0 Hz, J2 ¼ 1:0 Hz, 1H), 7.23 (d, J ¼ 8:5 Hz, 1H),
7.43 (td, J1 ¼ 7:5 Hz, J2 ¼ 1:0 Hz, 1H), 7.64 (dd,
J1 ¼ 8:5 Hz, J2 ¼ 2:0 Hz, 1H), 9.04 (d, J ¼ 8:0 Hz, 1H),
9.43 (d, J ¼ 2:0 Hz, 1H); 11.04 (s, 1H, NH). 13C (100 MHz,
DMSO-d6): 61.0 (CH2), 68.4, 69.7, 77.2, 80.1, 82.0
(CHsugar), 109.9, 113.3, 121.3, 129.8, 130.9, 133.6, 134.2
(CHarom:), 113.7, 121.4, 122.9, 130.4, 135.6, 141.2, 144.7
(Cquat: arom:), 166.6, 168.7 (C@O).
15. Spectral data of 21 obtained as a red solid (mp >300 °C):
IR (KBr): mNH;OH: 3424 cmꢀ1; mC@O: 1720, 1703 cmꢀ1; mC@C
:
1
1618 cmꢀ1. H (400 MHz, DMSO-d6): 3.30–3.45 (m, 3H),
3.47–3.58 (m, 1H), 3.80 (dd, 1H, J1 ¼ 10:5 Hz,
J2 ¼ 5:5 Hz), 3.76–3.95 (m, 1H), 4,70 (t, J ¼ 5:5 Hz, 1H,
OH), 5.21 (d, J ¼ 5:0 Hz, 1H, OH), 5.23 (d, J ¼ 4:5 Hz,
1H, OH), 5.45 (d, J ¼ 4:5 Hz, 1H, OH), 5.38–5.45 (br s,
0
1H, H1 ), 6.94 (d, J ¼ 7:7 Hz, 1H), 7.09 (td, J1 ¼ 8:0 Hz,
J2 ¼ 1:0 Hz, 1H), 7.47 (td, J1 ¼ 7:5 Hz, J2 ¼ 1:0 Hz, 1H),
7.51 (d, J ¼ 9:0 Hz, 1H), 8.38 (dd, J1 ¼ 9:0 Hz,
J2 ¼ 2:5 Hz, 1H), 9.05 (d, J ¼ 8:0 Hz, 1H), 10.21 (d,
J ¼ 2:5 Hz, 1H), 11.10 (s, 1H, NH). 13C (100 MHz,
DMSO-d6): 61.0 (CH2), 68.7, 69.7, 77.0, 80.2, 82.2
(CHsugar), 110.1, 111.7, 121.5, 124.2, 127.6, 130.0, 134.2
(CHarom:), 121.1, 121.2, 129.2, 136.9, 142.1, 145.2, 147.0
(Cquat: arom:), 167.1, 168.7 (C@O).
10. Typical procedure for preparation of 16: A solution of
glycosylisatine 13 (130 mg, 0.19 mmol) and oxindole
(26 mg, 0.19 mmol) in a mixture of acetic acid (0.4 mL),
and concentrated HCl (2.6 lL) was refluxed for 24 h. After
cooling, EtOAc was added to the mixture, the organic
phases were washed twice with H2O, dried over MgSO4,