G. V. M. Sharma et al. / Tetrahedron Letters 45 (2004) 7729–7732
7731
HOOC
COOH
HOOC
CHO
TCT, CH3CN, rt
2h
+
N
N
N
H
H
H
OCH3
3
14
14a (87%)
OCH3
Scheme 2.
+
H
N
H
OH
Cl
N
OH
O
Cl-
:OH2
N
N
N
N
N
N
N
+ 3 HCl
_ HCl
Cl
N
Cl
Cl
Cl
Cl
N
N
HO
Cl
OH
Figure 1.
In summary, we have developed an efficient TCT-cata-
lyzed protocol for the synthesis of bis(indolyl)alkanes
and bis(indolyl)glycoconjugates in short reaction times
under mild reaction conditions in high yields. The read-
ily available inexpensive TCT-catalyst makes this proto-
col an attractive method particularly for the synthesis of
unusual C-nucleoside conjugates.
1013cmÀ1 1H NMR (300MHz, CDCl3): d 10.30,
;
10.12 (2 br s, 2H), 7.64 (d, 1H, J = 6.5Hz), 7.49–7.33
(m, 1H), 7.20–6.76 (m, 8H), 5.95 (d, 1H, J = 5.3Hz),
4.95 (t, 2H, J = 17.1Hz), 4.45 (d, 1H, J = 5.3Hz), 3.29
(d, 1H, J = 4.2Hz) 3.08 (s, 3H), 1.67 (s, 3H), 1.25 (s,
3H); EIMS: (m/z, %) 245 (M+À173, 18), 233
(M+À185, 28), 117 (M+À301, 100), 90 (M+À328, 37);
Anal. Calcd for C25H26N2O4 (418): C, 71.75; H, 6.26.
Found: C, 71.80; H, 6.30.
2. General experimental procedure
3.3. 2-{-[3-Carboxymethyl-1H-2-indolyl(4-methoxyphen-
yl)methyl]-1H-3-indolyl}acetic acid 14a
To a solution of aldehyde (1mmol) in acetonitrile
(2mL), indole (2mmol) was added followed by catalytic
TCT (10mol%) at room temperature. After stirring the
reaction mixture for the specified time (Table 1), solvent
was removed under reduced pressure, the residue diluted
with water and extracted with ethyl acetate (3 · 5mL).
The combined organic layers were washed with water
(10mL), brine (10mL), dried (Na2SO4) and evaporated
under vacuum to give a crude product which was
purified by column chromatography (silica gel
5–20% EtOAc:hexane) to furnish the product.
Mp125–130 ꢁC; IR (KBR): 3400, 3385, 2980, 2938,
1730, 1502, 1308, 1161, 1071, 1013cmÀ1 1H NMR
;
(200MHz, CDCl3): d 10.48 (br s, 2H), 7.38 (d, 2H,
J = 6.0Hz), 7.28 (d, 2H, J = 5.0Hz), 7.12–6.90 (m,
8H), 6.78 (d, 2H, J = 8.0Hz), 6.08 (s, 1H), 3.75 (d,
3H), 3.54 (s, 4H); EIMS: (m/z, %) 468 (M+, 8),
361(M+À107, 100), 176 (M+À292, 63).
Acknowledgements
P.S. and J.J.R. thank the CSIR, New Delhi, India for
financial support.
3. Spectral data of selected compounds
3.1. 3-[1H-3-Indolyl(2-thienyl)methyl]-1H-indole 6a
Mp163–165 ꢁC; IR (KBR): 3375, 2982, 2930, 1505,
References and notes
1308, 1161, 1071, 1013cmÀ1 1H NMR (200MHz,
;
1. Sundberg, R. J. The Chemistry of Indoles; Academic: New
York, 1970.
CDCl3): d 7.85 (br s, 1H), 7.40 (d, 2H, J = 8.3Hz),
7.26 (t, 3H, J = 7.5Hz), 7.18–6.75 (m, 9H), 6.12 (s,
1H); EIMS: (m/z, %) 328 [M+, 23], 245 (M+À83, 100),
117 (42); Anal. Calcd for C21H96N2S (328): C, 76.80;
H, 4.91. Found: C, 76.78; H, 4.95.
2. (a) Porter, J. K.; Bacon, C. W.; Robins, J. D.; Himmels-
bach, D. S.; Higman, H. C. J. Agric. Food. Chem. 1977,
25, 88–93; (b) Osawa, T.; Namiki, M. Tetrahedron Lett.
1983, 24, 4719–4722; (c) Fahy, E.; Potts, B. C. M.;
Faulkner, D. J.; Smith, K. J. Nat. Prod. 1991, 54, 564–566;
(d) Bifulco, G.; Bruno, I.; Riccio, R.; Lavayre, J.; Bourdy,
G. J. Nat. Prod. 1995, 58, 1254–1260; (e) Bell, R.; Carmell,
S.; Sar, N. J. Nat. Prod. 1994, 57, 1587–1590; (f) Garbe, T.
R.; Kobayashi, M.; Shimizu, N.; Takesue, N.; Ozawa, M.;
Yukawa, H. J. Nat. Prod. 2000, 63, 596–598.
3.2. 3-{1H-3-Indolyl[6-deoxy-2,2-dimethyl-(3aR,5R,6S,-
6aR)-perhydrofuro[2,3-d][1,3]di-oxol-5-yl]methyl}-1H-
indole 11a
[a]D À16.9 (c 1.0, CHCl3); mp102–105 ꢁC; IR (KBR):
3. Remers, W. A. In Heterocyclic Compounds; Houlihan, W.
J., Ed.; Interscience Publishers: New York; 1972; pp 1–226.
3385, 2980, 2938, 1725, 1705, 1502, 1308, 1161, 1071,