S. Raju et al. / Bioorg. Med. Chem. Lett. 16 (2006) 6185–6189
6189
12. (a) Raju, S.; Batchu, V. R.; Swamy, N. K.; Dev, R. V.;
Babu, J. M.; Kumar, P. R.; Mukkanti, K.; Pal, M.
Tetrahedron Lett. 2006, 47, 83; (b) Raju, S.; Batchu, V. R.;
Swamy, N. K.; Dev, R. V.; Sreekanth, B. R.; Babu, J. M.;
Vyas, K.; Kumar, P. R.; Mukkanti, K.; Annamalai, P.;
Pal, M. Tetrahedron 2006, 62, 9554.
13. Nieves-Neira, W.; Rivera, M. I.; Kohlhagen, G.; Hursey,
M. L.; Pourquier, P.; Sausville, E. A.; Pommier, Y. Mol.
Pharmacol. 1999, 56, 478.
MeOH) 360.4, 267.4, 203.4; HPLC 99.3%, column:
Zorbax Eclipse XDB C-18 (150 · 4.6) mm, mobile phase
A: 0.05% TFA in water, mobile phase B: 0.05% TFA in
methanol, gradient (T/%B): 0/30, 13/70, 15/100, 25/100, flow
rate: 1.5 mL/min, UV 254 nm, retention time 12.8 min.
Spectral data for 3d: off-white solid; mp 63–64 ꢁC; 1H NMR
(CDCl3, 200 MHz) d 7.35–7.21 (m, 4H), 6.99–6.93 (m, 4H),
4.91 (s, 2H); IR (cmÀ1, CHCl3) 2923.3, 2216.2, 1595.8,
1486.3; m/z (ES mass) 215 (M+, 100%); 13C NMR (CDCl3,
50 MHz) d 157.7, 132.7 (2C), 129.4 (2C), 127.6, 126.9, 121.4,
114.9 (2C), 87.9, 80.4, 56.6 (CH2); UV (nm, MeOH) 359.8,
269.2, 202.4; HPLC 99.0%, column: Zorbax Eclipse XDB
C-18 (150 · 4.6) mm, mobile phase A: 0.05% TFA in water,
mobile phase B: 0.05% TFA in methanol, gradient (T/%B):
0/30, 13/70, 15/100, 25/100, flow rate: 1.5 mL/min, UV
254 nm, retention time 17.1 min.
14. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 16, 4467.
15. (a) Nikolai, A. B.; Ludmila, I. S.; Elena, V. L.; Tatiana, P.
T.; Irina, P. B. Tetrahedron Lett. 1996, 37, 897; (b) Van
den Hoven, B. G.; Alper, H. J. Org. Chem. 1999, 64, 9640,
and references cited therein.; (c) Oh, C. H.; Reddy, V. R.
Synlett 2004, 12, 2091; For preparation via Cu-free
Sonogashira coupling in ionic liquid, see: (d) Fukuyma,
T.; Shinmen, M.; Nishitani, S.; Sato, M.; Ryu, I. Org.
Lett. 2002, 4, 1691; For preparation via Sonogashira
coupling using controlled microwave heating, see: (e)
Erdelyl, M.; Gogoll, A. J. Org. Chem. 2001, 66, 4165.
16. (a) Batchu, V. R.; Subramanian, V.; Parasuraman, K.;
Swamy, N. K.; Kumar, S.; Pal, M. Tetrahedron 2005, 61,
9869; See also: (b) Pal, M.; Subramanian, V.; Batchu, V.
R.; Dager, I. Synlett 2004, 1965; (c) Pal, M.; Subramanian,
V.; Yeleswarapu, K. R. Tetrahedron Lett. 2003, 44, 8221.
17. In a typical procedure a mixture of 2-iodothiophene
(1.42 mmol), 10% Pd/C (0.037 mmol), PPh3 (0.28 mmol),
CuI (0.07 mmol), and ethanolamine (4.16 mmol) in water
(10 mL) was stirred at 25–30 ꢁC for 30 min under nitrogen.
The acetylinic compound (2.14 mmol) was added, and the
mixture was initially stirred at room temperature for 1 h
and then at 80 ꢁC for 8–10 h. After completion of the
reaction, the mixture was cooled to room temperature,
diluted with EtOAc (50 mL), and filterd through Celite.
The organic layers collected, washed with water (3·
25 mL), dried over anhydrous Na2SO4, and concentrated.
The crude residue was purified by column chromatogra-
phy on silica gel, using light petroleum (60–80 ꢁC)-ethyl
acetate to afford the desired product. Spectral data for 3a:
off-white solid; mp 54–55 ꢁC. 1H NMR (CDCl3, 200 MHz)
d 7.23 (d, J = 5.0 Hz, 1 H), 7.17 (d, J = 4.7 Hz, 1H), 6.93
(m, 1H), 2.05 (br s, –OH), 1.55 (s, 6H); IR (cmÀ1, CHCl3)
3239.1, 2980.1, 1256.0, 1217.9, 961.6; m/z (ES mass) 149
(M+ÀOH, 100%); 13C NMR (CDCl3, 50 MHz) d 132.2,
132.0, 127.2, 127.0, 94.7, 76.4, 65.5, 31.5 (2C); UV (nm,
18. The compound 1b was prepared according to the follow-
ing Scheme see: (a) Campaigne, E.; Monroe, P. A. J. Am.
Chem. Soc. 1954, 76, 2447; (b) Ishikawa, T.; Mizutani, A.;
Miwa, C.; Oku, Y.; Komano, N.; Takami, A.; Watanabe,
T. Heterocycles 1997, 45, 2261.
O
1. NaOH/Br2
2. H2O
3. AC2O
O
O
O
OH
HN
NH2
HN
ICl
1. SOCl2, reflux
2. Aq.NH3
CH3
CH3
I
AcOH, 80oC
S
S
S
S
1b
19. For further mechanistic discussion, see: (a) Pal, M.;
Subramanian, V.; Parasuraman, K.; Yeleswarapu, K. R.
Tetrahedron 2003, 59, 9563; (b) Subramanian, V.; Batchu,
V. R.; Barange, D.; Pal, M. J. Org. Chem. 2005, 70, 4778.
20. (a) Kloetzel, M. C.; Little, J. E.; Frisch, D. M., Jr. J. Org.
Chem. 1953, 18, 1511; (b) Asprou, C. M.; Brunskill, J. S.
A.; Jeffrey, H.; De, A. J. Heterocyl. Chem. 1980, 17, 87; (c)
Napier, R. P.; Kaufman, H. A.; Driscoll, P. R. J.
Heterocyl. Chem. 1970, 7, 393.
21. The 4-keto-4,5,6,7-tetrahydrothianaphthene is a key inter-
mediate for the synthesis of a range of sulfur-containing
compounds, see: Mosti, L.; Schenone, P.; Menozzi, G.;
Romussi, G. J. Heterocyl. Chem. 1982, 19, 1057, See also
Ref. 19a–b..
22. (a) Monks, A.; Scudiero, D.; Skehan, P.; Shoemaker, R.;
Paull, K.; Vistica, D.; Hose, C.; Langley, J.; Cronise, P.;
Vaigro-Wolff, A.; Gray-Goodrich, M.; Campbell, H.;
Mayo, J.; Boyd, M. J. Natl. Cancer Inst. 1991, 83, 757;
(b) For protocol for in vitro cell growth assay, please see
Ref. 12b.