W.-Y. Shao et al. / Tetrahedron Letters 47 (2006) 4085–4089
4089
11. Look, G. C.; Murphy, M. M.; Campbell, D. A.; Gallop,
M. A. Tetrahedron Lett. 1995, 36, 2937–2940.
12. Zinieris, N.; Leondiadis, L.; Ferderigos, N. J. Comb.
Chem. 2005, 7, 4–6.
6.48 (d, 1H, J = 16 Hz), 6.50 (d, 1H, J = 16 Hz), 6.87 (d,
2H, J = 8.5 Hz), 6.92 (d, 2H, J = 8.5 Hz), 7.45 (d, 2H,
J = 9 Hz), 7.51 (d, 2H, J = 9 Hz), 7.60 (d, 1H, J = 16 Hz),
7.62 (d, 1H, J = 16 Hz). ESI-MS m/z: 321.17 (MÀH)ÀÅ
.
1
13. General procedure: A mixture of 6 equiv of 1st aromatic
aldehyde and 2.5 equiv of DIEA in DCM was added to a
pre-swollen resin (1.0 mmol/g) at rt and reacted for 12 h.
After washed with DCM, the resin was capped with
DCM/MeOH/DIEA (80:15:5) for 2 · 15 min and dried.
To synthesize b-diketone curcumin derivatives, 20 equiv of
acetylacetone and 15 equiv of boric anhydride (B2O3) were
first mixed in DMF for 1 h at 70 ꢁC. The resultant white
powder and 15 equiv of tributyl borate were added to the
aldehyde-bound resin in DMF, and 2 equiv of butylamine
as catalyst at 50 ꢁC for 12 h. The resin was then washed
with DMF five times and split into several parts. To each
part, 15 equiv of another aldehyde, 10 equiv of tributyl
borate, and 1 equiv of butylamine were added at 50 ꢁC.
After 12 h, 0.4 N HCl was used to decompose the
acetylacetone–boron complex at 60 ꢁC for 2 h. The resin
was washed with DMF, MeOH, and dried under N2. The
final products were cleaved with DCM/TFA/MeOH
(5:1:1). For monoketone curcumin derivatives, the proce-
dure does not include the composition/decomposition of
the acetylacetone–boron complex. Each step is allowed to
be repeated two or more times if necessary.
2d: H NMR (500 MHz, CDCl3, ppm): 5.82 (s, 1H,enol),
6.50 (d, 1H, J = 16 Hz), 6.62 (d, 1H, J = 16 Hz), 6.87 (d,
2H, J = 8.5 Hz), 7.38–7.40 (m, 3H), 7.46 (d, 2H,
J = 8.5 Hz), 7.55–7.57 (m, 2H), 7.62 (d, 1H, J = 16 Hz),
7.65 (d, 1H, J = 16 Hz). ESI-MS m/z: 291.1 (MÀH)ÀÅ. 2e:
1H NMR (500 MHz, CDCl3, ppm): 5.76 (s, 1H, enol), 6.41
(d, 1H, J = 15.5 Hz), 6.48 (d, 1H, J = 15.5 Hz), 6.85 (d,
2H, J = 8.5 Hz), 7.06 (dd, 1H, J = 5, 4 Hz), 7.26 (d, 1H,
J = 4 Hz), 7.38 (d, 1H, J = 5 Hz), 7.46 (d, 2H, J = 8.5 Hz),
7.61 (d, H, J = 16 Hz), 7.76 (d, 1H, J = 16 Hz). ESI-MS
m/z 297.0 (MÀH)ÀÅ. Elem. Anal. Calcd for C17H14O3S: C,
68.44; H, 4.73. Found: C, 68.31; H, 4.95. 2f: 1H NMR
(500 MHz, CDCl3, ppm): 5.86 (s, 1H, enol), 6.51 (d, 1H,
J = 16 Hz), 6.56 (d, 1H, J = 16 Hz), 6.86 (d, 2H,
J = 8.5 Hz), 7.21 (td, 1H, J = 8, 1.5 Hz), 7.33 (t, 1H,
J = 7.5 Hz), 7.47 (d, 2H, J = 8.5 Hz), 7.61–7.65 (m, 3H),
7.99 (d, 1H, J = 15.5 Hz). ESI-MS m/z 369.0, 371.0
(MÀH)ÀÅ. Elem. Anal. Calcd for C19H15O3Br: C, 61.47;
H, 4.07. Found: C, 61.35; H, 4.34. 2g: 1H NMR
(500 MHz, CDCl3, ppm): 1.82 (penta, 2H, J = 6 Hz),
2.92–2.94 (m, 4H), 6.70 (s, 2H), 6.90 (d, 2H, J = 8.5 Hz),
7.39 (d, 2H, J = 8.5 Hz), 7.72 (s, 1H), 7.76 (s, 1H). ESI-
MS m/z 379.2 (MÀH)ÀÅ. Elem. Anal. Calcd for C23H24O5:
C, 72.61; H, 6.36. Found: C, 72.35; H, 6.34. 2h: 1H NMR
(500 MHz, CDCl3, ppm): 1.81 (penta, 2H, J = 6.5 Hz),
2.87–2.96 (m, 4H), 3.90 (s, 3H), 6.88 (d, 2H, J = 8.5 Hz),
6.92 (d, 1H, J = 8.5 Hz), 6.99 (d, 1H, J = 1.5 Hz), 7.03
(dd, 1H, J = 8.5, 1.5 Hz), 7.36 (d, 2H, J = 9 Hz), 7.70 (s,
14. Pavolini, T.; Gambarin, F.; Grinzato, A. M. Ann. Chim.
1950, 40, 280–291.
15. Gerhard, M.; Lothar, B.; Antonio, A. Z. Chem. 1987, 27,
172–173.
1
16. 1a: H NMR (500 MHz, CDCl3, ppm): 3.95 (s, 3H), 5.84
(s, 1H, enol), 6.50 (d, 1H, J = 16 Hz), 6.62 (d, 1H,
J = 16 Hz), 6.93 (d, 1H, J = 8 Hz), 7.06 (s, 1H), 7.12 (d,
1H, J = 8 Hz), 7.37–7.40 (m, 3H), 7.55 (d, 2H, J = 8 Hz),
7.61 (d, 1H, J = 16 Hz), 7.65 (d, 1H, J = 16 Hz). ESI-MS
m/z: 321.1 (MÀH)ÀÅ. 1b: 1H NMR (500 MHz, CDCl3,
ppm): 3.88 (s, 3H), 5.72 (s, 1H, enol), 6.41 (d, 1H,
J = 16 Hz), 6.42 (d, 1H, J = 16 Hz), 6.78 (d, 2H,
J = 8.5 Hz), 6.86 (d, 1H, J = 8 Hz), 6.98 (d, 1H, J =
1.5 Hz), 7.05 (dd, 1H, J = 8, 1.5 Hz), 7.39 (d, 2H,
J = 8.5 Hz), 7.52 (d, 1H, J = 16 Hz), 7.54 (d, 1H,
J = 16 Hz). ESI-MS m/z: 337.0 (MÀH)ÀÅ. 1c: 1H NMR
(500 MHz, CDCl3, ppm): d 3.85 (s, 3H), 3.95 (s, 3H), 5.79
(s, 1H, enol), 6.47 (d, 1H, J = 16 Hz), 6.49 (d, 1H,
J = 16 Hz), 6.91 (d, 2H, J = 8.5 Hz), 6.93 (d, 1H,
J = 8 Hz), 7.05 (d, 1H, J = 2 Hz), 7.12 (dd, 1H, J = 8,
2 Hz), 7.50 (d, 2H, J = 9 Hz), 7.59 (d, 1H, J = 16 Hz), 7.62
(d, 1H, J = 16.5 Hz). ESI-MS m/z: 351.1 (MÀH)ÀÅ. 1d: 1H
NMR (500 MHz, CDCl3, ppm): 2.37 (s, 3H), 3.94 (s, 3H),
5.75 (s, 1H, enol), 6.09 (d, 1H, J = 3 Hz), 6.43 (d, 1H,
J = 16 Hz), 6.46 (d, 1H, J = 16 Hz), 6.51 (d, 1H,
J = 3.5 Hz), 6.92 (d, 1H, J = 8 Hz), 7.03 (s, 1H), 7.11
(dd, 1H, J = 8, 2 Hz), 7.34 (d, 1H, J = 16 Hz), 7.57 (d, 1H,
J = 16 Hz). ESI-MS m/z: 325.0 (MÀH)ÀÅ. Elem. Anal.
Calcd for C191H18O5: C, 69.93; H, 5.56. Found: C, 69.68;
H, 5.90. 2a: H NMR (500 MHz, CDCl3, ppm): 3.89 (s,
3H), 3.90 (s, 6H), 5.82 (s, 1H, enol), 6.49 (d, 1H,
J = 15 Hz), 6.52 (d, 1H, J = 15 Hz), 6.78 (s, 2H), 6.86
(d, 2H, J = 8.5 Hz), 7.45 (d, 2H, J = 8.5 Hz), 7.56 (d, 2H,
J = 15.5 Hz), 7.61 (d, 2H, J = 16 Hz). ESI-MS m/z: 381.0
(MÀH)ÀÅ. Elem. Anal. Calcd for C22H22O6: C, 69.10; H,
1
1H), 7.71 (s, 1H). ESI-MS m/z: 335.27 (MÀH)ÀÅ. 3a: H
NMR (500 MHz, CDCl3, ppm): 3.89 (s, 3H), 3.91 (s, 6H),
4.67 (s, 2H), 5.79 (s, 1H, enol), 6.39 (d, 1H, J = 3.5 Hz),
6.52 (d, 1H, J = 15.5 Hz), 6.53 (d, 1H, J = 15.5 Hz), 6.57
(d, 1H, J = 3.5 Hz), 6.78 (s, 2H), 7.38 (d, 1H, J = 16 Hz),
7.57 (d, 1H, J = 16 Hz). EI-MS m/z: 386 (M+Å), 368, 337,
234. Elem. Anal. Calcd for C21H22O7: C, 65.28; H, 5.74.
Found: C, 65.15; H, 5.98. Compound 3b: 1H NMR
(500 MHz, CDCl3, ppm): 3.05 (s, 6H), 4.66 (s, 2H), 5.74 (s,
1H, enol), 6.38 (d, 1H, J = 4 Hz), 6.46 (d, 1H,
J = 15.5 Hz), 6.51 (d, 1H, J = 15.5 Hz), 6.53 (d, 1H,
J = 3.5 Hz), 6.82 (br d, 2H), 7.34 (d, 1H, J = 15.5 Hz),
7.48 (d, 2H, J = 9 Hz), 7.62 (d, 1H, J = 15 Hz). EI-MS
m/z: 339 (M+Å), 243, 174. HRMS-EI m/z: calcd for
C20H21O4N, 339.1465; found, 339.1461. 3c: 1H NMR
(500 MHz, CDCl3, ppm): 3.94 (s, 3H), 4.66 (s, 2H), 5.75
(s, 1H, enol), 6.38 (d, 1H, J = 3.5 Hz), 6.47 (d, 1H, J =
16 Hz), 6.50 (d, 1H, J = 16 Hz), 6.55 (d, 1H, J = 2 Hz),
6.92 (d, 1H, J = 8.5 Hz), 7.04 (d, 2H, J = 1.5 Hz), 7.11
(dd, 1H, J = 8, 2 Hz), 7.36 (d, 1H, J = 15.5 Hz), 7.58 (d,
1H, J = 15.5 Hz). EI-MS m/z: 342 (M+Å), 324, 293, 217,
177. Elem. Anal. Calcd for C19H18O6: C, 66.66; H, 5.30.
Found: C, 66.66; H, 5.53. 3d: 1H NMR (500 MHz, CDCl3,
ppm): 4.66 (s, 2H), 5.79 (s, 1H, enol), 6.39 (d, 1H,
J = 3 Hz), 6.53 (d, 1H, J = 15.5 Hz), 6.57 (d, 1H,
J = 3.5 Hz), 6.61 (d, 1H, J = 15.5 Hz), 7.37–7.40 (m,
4H), 7.54–7.56 (m, 2H), 7.65 (d, 1H, J = 16 Hz). EI-MS
m/z: 296 (M+Å), 278, 265, 131. Elem. Anal. Calcd for
C18H16O4: C, 72.96; H, 5.44. Found: C, 72.74; H, 5.75.
Compound 3e: 1H NMR (500 MHz, CDCl3, ppm): 3.84
(s, 3H), 4.66 (s, 2H), 5.75 (s, 1H, enol), 6.38 (d, 1H,
J = 3 Hz), 6.49 (d, 1H, J = 16 Hz), 6.51 (d, 1H, J =
15.5 Hz), 6.55 (d, 1H, J = 3.5 Hz), 6.91 (d, 2H,
J = 8.5 Hz), 7.36 (d, 1H, J = 15 Hz), 7.50 (d, 2H,
J = 9 Hz), 7.61 (d, 1H, J = 16 Hz). EI-MS m/z: 326
(M+Å), 308, 161. Elem. Anal. Calcd for C19H18O5: C,
69.93; H, 5.56. Found: C, 69.71; H, 5.97.
1
5.80. Found: C, 68.85; H, 6.03. 2b: H NMR (500 MHz,
CDCl3, ppm): 3.05 (s, 6H), 5.76 (s, 1H, enol), 6.43 (d, 1H,
J = 16 Hz), 6.47 (d, 1H, J = 15.5 Hz), 6.68 (d, 2H,
J = 9 Hz), 6.85 (d, 2H, J = 8.5 Hz), 7.44–7.47 (m, 4H),
7.58 (d, 1H, J = 16 Hz), 7.62 (d, 1H, J = 15.5 Hz). ESI-
MS m/z: 334.19 (MÀH)ÀÅ. HRMS-EI m/z: calcd for
C21H21O3N, 335.1516; found 335.1520. 2c: 1H NMR
(500 MHz, CDCl3, ppm): 3.85 (s, 3H), 5.78 (s, 1H, enol),