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LETTER
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collected analytical data were in perfect agreement with the
data reported in this preparation.
(12) (a) Yang, H.; Hu, G.-Y.; Chen, J.; Wang, Y.; Wang, Z.-H.
Bioorg. Med. Chem. Lett. 2007, 17, 5210. (b) Cason, J.
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(13) Reactions carried out without cadmium led to a mixture of
compounds presenting the double addition of the methyl
moiety and the expected mono-alkylated product 11.
(14) The structures of the final compounds were fully
characterized by NMR spectroscopy. They presented NOEs
between H-3 and the methyl and between the methyl and the
hydroxy function as depicted in the isobenzofuran-(3H)-one
model (see Scheme 2).
(15) Margarita, R.; Mercanti, C.; Parlanti, L.; Piancatelli, G.
Eur. J. Org. Chem. 2000, 1865.
(16) See the Supporting Information for the preparation of
compound 3.
(17) 3-Hydroxy-5-{[(2E,5E)-7-hydroxy-3,7-dimethylocta-2,5-
dien-1-yl]oxy}-7-methoxy-3,6-dimethylisobenzofuran-
1(3H)-one (4)
(2) (a) Faccini, L.; Martino, R.; Ferrari, A.; Piñana, J. L.;
Valcárel, D.; Barba, P.; Granell, M.; Delgado, J.; Briones, J.;
Sureda, A.; Brunet, S.; Sierra, J. Eur. J. Haematol. 2012, 88,
46. (b) Qiu, W.; Carson-Walter, E. B.; Liu, H.; Epperly, M.;
Greenberger, J. S.; Zambetti, G. P.; Zhang, L.; Yu, J. Cell
Stem Cell 2008, 2, 576. (c) Royer, B.; Larosa, F.; Legrand,
F.; Gerritsen-van Schieveen, P.; Berard, M.; Kantelip, J.-P.;
Deconinck, E. Biol. Blood Marrow Transpl. 2009, 15, 1134.
For articles related to growth factors, see: (d) Beaven, A. W.;
Shea, T. C. Drugs Today 2007, 43, 461. (e) Stiff, P. Nature
2001, 27, S3. (f) de Koning, B. A.; Philipsen-Geerling, B.;
Hoijer, M.; Buller, H. A.; Pieters, R. Pediatr. Blood Cancer
2007, 48, 532. (g) Wymenga, A. N.; van der Graaf, W. T.;
Hofstra, L. S.; Spijkervet, F. K.; Timens, W.; Timmer-
Bosscha, H.; Sluiter, W. J.; van Buuren, A. H.; Mulder, N.
H.; de Vries, E. G. Clin. Cancer Res. 1999, 5, 1363; and
references therein.
(3) (a) Gerull, S.; Arber, C.; Bucher, C.; Buser, A.; Gratwohl,
A.; Halter, J.; Heim, D.; Tichelli, A.; Stern, M. Bone Marrow
Transpl. 2011, 46, 740. (b) Uharek, L.; Gassmann, W.;
Fleischhauer, D.; Wottge, H. U.; Loeffler, H.; Mueller-
Ruchholtz, W. Bone Marrow Transpl. 1991, 7, 17.
(4) Ruffner, H.; Sprunger, J.; Charlat, O.; Leighton-Davies, J.;
Grosshans, B.; Salathe, A.; Zietzling, S.; Beck, V.; Therier,
M.; Isken, A.; Xie, Y.; Zhang, Y.; Hao, H.; Shi, X.; Liu, D.;
Song, Q.; Clay, I.; Hintzen, G.; Tchorz, J.; Bouchez, L. C.;
Michaud, G.; Finan, P.; Myer, V. E.; Bouwmeester, T.;
Porter, J.; Hild, M.; Bassilana, F.; Parker, C. N.; Cong, F.
PLoS One 2012, 7, e40976.
To a stirring suspension of KSCN (84 mg, 0.866 mmol) in
MeCN (1 mL), (PhSe)2 (108 mg, 0.346 mmol) followed by
BAIB (139 mg, 0.433 mmol) were added. The cloudy yellow
mixture was stirred at r.t. for 10 min before the addition of a
solution of compound 2 (104 mg, 0.289 mmol) in MeCN (1
mL). The resulting mixture was stirred at r.t. for 16 h. After
completion of the reaction, the mixture was washed with sat.
NaHCO3–10% Na2S2O3 solution (5 mL) and extracted with
EtOAc (2 × 50 mL). The organic layer was washed with
brine (2 × 50 mL), dried over Na2SO4, filtered and the
volatiles evaporated under reduced pressure to afford the
expected intermediate, (E)-3-hydroxy-5-{[7-isothiocyanato-
3,7-dimethyl-6-(phenylselanyl)oct-2-en-1-yl]oxy}-7-
methoxy-3,6-dimethylisobenzofuran-1(3H)-one as a yellow
oil. Next, to a stirring mixture of NaHCO3 (10.97 mg, 0.131
mmol) and NaIO4 (55.8 mg, 0.261 mmol) in H2O (4 mL) was
added a solution of the phenylselenyl intermediate (50 mg,
0.087 mmol) in 1,4-dioxane (8 mL). The cloudy mixture was
stirred overnight at r.t. Upon completion, the mixture was
washed with sat. NH4Cl solution (2 mL) and extracted with
EtOAc (2 × 25 mL). The organic layer was washed with
brine (2 × 50 mL), dried over Na2SO4, filtered and
concentrated under reduced pressure. The crude residue was
purified on silica gel (FC ISCO, gradient elution: 0–70%
EtOAc in heptane) to afford compound 4 as a colorless oil
(18 mg, 0.048 mmol, 55% yield). 1H NMR (400 MHz,
DMSO-d6): δ = 7.57 (s, 1 H, exchangeable with D2O), 7.02
(s, 1 H), 5.59 (d, J = 14.95 Hz, 1 H), 5.51–5.49 (m, 2 H),
4.73–4.70 (m, 2 H), 4.48 (s, 1 H, exchangeable with D2O),
3.90 (s, 3 H), 2.72 (d, J = 6.35 Hz, 2 H), 2.05 (s, 3 H), 1.71
(s, 3 H), 1.70 (s, 3 H), 1.16 (s, 6 H, 2 × CH3). 13C NMR (100
MHz, CDCl3): δ = 166.4, 163.9, 157.7, 151.7, 141.1, 140.0,
124.6, 122.6, 120.4, 109.7, 104.2, 100.6, 71.4, 66.1, 62.5,
42.2, 30.4, 30.0, 26.6, 17.4, 9.3. LC–MS: m/z = 377 [ M +
H]+; tR = 1.03 min (>99% by LC–MS, UV). ROESY
correlation data are reported in the Supporting Information.
(5) Compounds were tested in an 8-point-dilution manner.
Values are given for the EC50 corresponding to the
maximum relative luciferase activity. Data related to
compounds 1 and 3 are not shown.
(6) (a) Neuman, F.; Graef, T.; Tapprich, C.; Vaupel, M.; Steidl,
U.; Germing, U. Bone Marrow Transpl. 2005, 35, 1089.
(b) Pohlreich, D.; Vitek, A.; Maalouf, J.; Cetkovsky, P. Bone
Marrow Transpl. 2006, 37, 235.
(7) Shim, S. H.; Sy, A. A.; Gloer, J. B.; Wicklow, D. T. Bull.
Korean Chem. Soc. 2008, 29, 863.
(8) (a) Yang, X.-L.; Zhang, S.; Hu, Q.-B.; Luo, D.-Q.; Zhang, Y.
J. Antibiot. 2011, 64, 723. (b) Gamboa-Angulo, M. M.;
Escalente-Erosa, F.; Garcia-Sosa, K.; Alejo-Gonzalez, F.;
Delgado-Lamas, G.; Pena-Rodriguez, L. M. J. Agric. Food
Chem. 2002, 50, 1053. (c) Hariprakasha, H. K.; Rao, G. S. S.
Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.
1998, 37, 851; and references therein.
(9) (a) Kraft, P.; Bruneau, A. Eur. J. Org. Chem. 2007, 2257.
(b) See also: Patterson, J. J. Org. Chem. 1995, 60, 560.
(10) Paz, J. L.; Rodrigues, J. A. R. J. Braz. Chem. Soc. 2003, 14,
975.
(11) The synthesis of the side chain corresponding to compound
9c was reported in the following patent: Skattebol, L.;
Aukrust, I. R.; Sandberg, M. WO2011117324 A2, 2011. The
Synlett 2013, 24, 2397–2400
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