S. Padakanti et al. / Tetrahedron 59 (2003) 7915–7920
7919
Kargman, S.; Kennedy, B.; Leblanc, Y.; Leger, S.; Mancini, J.;
O’Neill, G. P.; Ouellet, M.; Percival, M. D.; Perrier, H.;
Riendeau, D.; Rodger, I.; Tagari, P.; Therien, M.; Vickers, P.;
Wong, E.; Xu, L.-J.; Young, R. N.; Zamboni, R.; Boyce, S.;
Rupniak, N.; Forrest, M.; Visco, D.; Patrick, D. Bioorg. Med.
Chem. Lett. 1999, 9, 1773. (b) Chan, C.-C.; Boyce, S.;
Brideau, C.; Charleson, S.; Cromlish, W.; Ethier, D.; Evans, J.;
Ford-Hutchinson, A. W.; Forrest, M. J.; Gauthier, J. Y.;
Gordon, R.; Gresser, M.; Guay, J.; Kargman, S.; Kennedy, B.;
Leblanc, Y.; Leger, S.; Mancini, J.; O’Neill, G. P.; Ouellet, M.;
Patrick, D.; Percival, M. D.; Perrier, H.; Prasit, P.; Rodger, I.;
Tagari, P.; Therien, M.; Vickers, P.; Visco, D.; Wang, Z.;
Webb, J.; Wong, E.; Xu, L.-J.; Young, R. N.; Zamboni, R.;
Riendeau, D. J. Pharmacol. Exp. Ther. 1999, 290, 551.
(250 mL) was added DBU (38.4 ml, 0.258 mol) slowly over
15 min under a nitrogen atmosphere at 258C. The mixture
was stirred for 0.5 h at 258C and then heated to reflux for
18 h. The mixture was cooled to room temperature, diluted
with water (100 mL) and 2N HCl (50 mL) and then
extracted with EtOAc (3£100 mL). The organic layers
were collected, combined, washed with water (2£100 mL)
and dried over anhydrous Na2SO4. After removal of solvent
under vacuum the crude product was purified by column
chromatography over silica gel using 6% EtOAc–petro-
leum ether (400 ml) to give the desired product (10 g, 54%
yield) as a white semisolid; 1H NMR (CDCl3) 7.63 (d,
J¼8.3 Hz, 2H), 7.28 (d, J¼8.3 Hz, 2H), 5.11–5.05 (m, 1H,
CHMe2), 2.52 (s, 3H, SCH3), 1.64 (s, 6H, CH3), 1.27 (d,
J¼6.3 Hz, 6H, CH3); 13C NMR (CDCl3, 50 MHz) d 165.74,
141.18, 140.09, 139.07, 134.97, 128.17 (2C), 127.05 (2C),
85.91, 73.06, 26.61 (2C), 22.08 (2C), 15.90; IR (KBr,
cm21): 1752 (s, CvO), 1627 (s, CvC), 1593 (s); MS (CI,
i-Butane): 292 (Mþ, 25), 250 (80), 177 (100%); Anal. calcd
for C16H20O3S: C, 65.73; H, 6.89. Found: C, 65.70; H, 6.90.
3. (a) Hla, T.; Neilson, K. Proc. Natl. Acad. Sci. USA 1992, 89,
7384. (b) Holtzman, M. J.; Turk, J.; Shornick, L. P. J. Biol.
Chem. 1992, 267, 21438. (c) Griswold, D. E.; Adams, J. L.
Med. Res. Rev. 1996, 16, 181. (d) Masferrer, J. L.; Seibert, K.;
Zweifel, B.; Neddleham, P. Proc. Natl. Acad. Sci. USA 1992,
89, 3917. (e) Allison, M. C.; Howatson, A. G.; Torrance, C. J.;
Lee, F. D.; Russell, R. I. N. Engl. J. Med. 1992, 327, 749.
4. (a) Pal, M.; Rao, Y.K.; Rajagopalan, R.; Misra, P.; Kumar,
P.M.; Rao, C.S. World Patent Application WO 01/90097, Nov
29, 2001. (b) Pattabiraman, V. R.; Padakanti, P. S.; Veer-
amaneni, V. R.; Pal, M.; Yeleswarapu, K. R. Synlett 2002, 947.
(c) Padakanti, S.; Veeramaneni, V. R.; Pattabiraman, V. R.;
Pal, M.; Yeleswarapu, K. R. Tetrahedron Lett. 2002, 43, 8715.
(d) Pal, M.; Rao, V. V.; Srinivas, P.; Murali, N.; Akhila, V.;
Premkumar, M.; Rao, C. S.; Misra, P.; Ramesh, M.; Rao, Y. K.
Indian J. Chem. 2003, 42B, 593. (e) Pal, M.; Veeramaneni,
V. R.; Nagaballi, M.; Kalleda, S. R.; Misra, P.; Casturi, S. R.;
Yeleswarapu, K. R. Bioorg. Med. Chem. Lett. 2003, 13, 1639.
5. Synthesis from a-haloketone and arylacetic acid (a) Dikshit,
D. K.; Shing, S.; Sing, M. M.; Kamboj, V. P. Indian J. Chem.
1990, 10B, 954. (b) Vijayaraghavan, S. T.; Balasubramanian,
T. R. Indian J. Chem. 1986, 25B, 760. (c) Wakharkar, R. D.;
Deshpande, V. H.; Landge, A. B.; Upadhye, B. K. Synth.
Commun. 1987, 17, 1513. Synthesis via magnesium mediated
carbometallation of propargyl alcohols: (d) Forgione, P.;
Wilson, P. D.; Fallis, A. G. Tetrahedron Lett. 2000, 41, 17. and
references cited therein. Synthesis by palladium catalyzed
reactions (e) Crisp, G. T.; Meyer, A. G. J. Org. Chem. 1992,
57, 6972. (f) Mahon, R.; Richecoeur, A. M. E.; Sweeney, J. B.
J. Org. Chem. 1999, 64, 328. (g) Rossi, R.; Bellina, F.; Raugei,
E. Synlett 2000, 1749, and references cited therein.
4.1.7. Preparation of 3-isopropoxy-5,5-dimethyl-4-(4-
methylsulfonylphenyl)-2,5-dihydro-2-furanone (1). To a
solution of 3-isopropoxy-5,5-dimethyl-4-(4-methylsulfanyl-
phenyl)-2,5-dihydro-2-furanone (10 g, 0.034 mol) in
acetone (200 mL) was added a solution of oxone (52.60 g,
0.086 mol) in water (200 mL). The reaction mixture was
stirred vigorously for 3 h at 258C. After completion of the
reaction the solvent was removed under reduced pressure
and water (200 mL) was added. The mixture was then
extracted with EtOAc (2£100 mL), organic layers collected,
combined, dried over anhydrous Na2SO4 and concentrated
under vacuum to give the title compound (11 g, 99% yield)
as an off white powder, mp 126–1278C; 1H NMR (CDCl3)
7.98 (d, J¼8.8 Hz, 2H), 7.83 (d, J¼8.8 Hz, 2H), 5.28–5.20
(m, 1H), 3.07 (s, 3H), 1.64 (s, 6H), 1.26 (d, J¼6.7 Hz, 6H);
13C NMR (CDCl3, 50 MHz) d 166.14, 140.78, 140.05,
139.97, 135.37, 128.47 (2C), 127.15 (2C), 82.91, 73.36,
43.93, 26.38 (2C), 22.28 (2C); IR (KBr, cm21): 1747 (s),
1652 (s), 1595 (s); MS (CI, i-Butane): 325 (Mþ, 100), 283
(40), 237 (20%). HPLC: 97.56%, Novapak C18 (150 mm),
water–acetonitrile (50:50), 1 mL/min, 290 nm, retention
time: 4.76 min. Anal. calcd for C16H20O5S: C, 59.24; H,
6.21. Found: C, 59.20; H, 6.22.
´
´
6. (a) Therien, M.; Gauthier, J. Y.; Leblanc, Y.; Leger, S.;
Perrier, H.; Prasit, P.; Wang, Z. Synthesis 2001, 1778. (b) For a
list of methods see: Sorbera, L. A.; Rabasseda, X.; Castaner, J.
Drugs Future 1998, 23, 1287.
Acknowledgements
The authors thank Dr A. Venkateswarlu, Dr R. Rajagopalan
and Professor J. Iqbal for their constant encouragement and
the Analytical Department for spectral support.
7. Leblanc, Y.; Roy, P.; Wang, Z.; Li, C. S.; Chauret, N.; Nicoll-
Griffith, D. A.; Silva, J. M.; Aubin, Y.; Yergey, J. A.; Chan,
C. C.; Riendeau, D.; Brideau, C.; Gordon, R.; Xu, L.; Webb, J.;
Visco, D. M.; Prasit, P. Bioorg. Med. Chem. Lett. 2002, 12, 3317.
8. For the generation of methylsulfonyl carbanion from MeSO2-
moiety in the presence of a base such as NaH or KOtBu and its
subsequent reaction with carbonyl group, see: (a) House, H. O.;
Larson, J. K. J. Org. Chem. 1968, 33, 61. (b) Becker, H.-D.;
Russell, G. A. J. Org. Chem. 1963, 28, 1896. (c) For the
cleavage of similar type of ester linkage, see: House, H. O.;
Wilkins, J. M. J. Org. Chem. 1976, 41, 3067. (d) Aakel, L. E.;
Launay, F.; Atlamsani, A.; Bregeault, J.-M. Chem. Commun.
2001, 21, 2218.
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