Q. Zhang, Y. Wu / Tetrahedron 63 (2007) 10407–10414
10413
(film) 3458, 1707, 1453, 1098, 1027, 946, 847, 738,
dissolved in DME (10 mL). UHP (416 mg, 4.43 mmol)
and p-TsOH$H2O (135 mg, 0.71 mmol) were added. The
mixture was stirred at ambient temperature for 3 d before be-
ing diluted with Et2O, washed with water and brine, and
dried over anhydrous Na2SO4. Removal of the solvent and
chromatography on silica gel (4:1 PE/EtOAc) afforded 21
as a colorless oil (132 mg, 0.44 mmol, 75% from 20, not
1
698 cmꢀ1; H NMR (300 MHz, CDCl3) d 7.34–7.25 (m,
5H), 4.84 (t, J¼4.7 Hz, 2H), 4.49 (s, 2H), 3.98–3.81 (m,
4H), 3.46 (t, J¼6.2 Hz, 2H), 2.35–2.26 (m, 2H), 2.17–2.11
(m, 2H), 1.89–1.54 (m, 6H), 1.37–1.22 (m, 5H); 13C NMR
(75 MHz, CDCl3) d 213.4, 138.7, 128.3, 127.6, 127.4,
104.7, 72.8, 70.6, 64.8, 50.9, 50.8, 35.6, 31.5, 29.7, 27.5,
25.9, 25.6, 23.7; ESIMS m/z 369.3 ([M+Na]+); EIHRMS
calcd for C21H30O4 (M+) 346.2144, found 346.2146.
1
very stable and should be used as soon as possible). H
NMR (300 MHz, CDCl3) d 7.55 (s, 0.71H), 7.29 (s,
0.12H), 7.00 (dt, J¼15.4, 7.0 Hz, 1H), 5.85 (d, J¼15.7 Hz,
1H), 4.18 (q, J¼7.0 Hz, 2H), 3.98–3.67 (m, 2H), 2.32–
2.25 (m, 1H), 2.18–1.73 (m, 8H), 1.50–1.15 (m, 10H).
4.1.12. Conversion of 19 into 20. Aq HCl (1 M) was added
to a solution of 19 (280 mg, 0.81 mmol) in THF (10 mL).
The mixture was heated in a 60 ꢁC bath for 2 h. After being
cooled to ambient temperature the mixture was diluted with
Et2O, washed with satd aq NaHCO3, water, and brine, and
dried over anhydrous Na2SO4. Removal of the solvent left
a residue, which was dissolved in CH2Cl2 (5 mL).
Ph3P]CHCO2Et (425 mg, 1.22 mmol) was added. The
mixture was stirred at ambient temperature overnight. The
solvent was removed by rotary evaporation. The residue
was diluted with Et2O. The solids were filtered off. The fil-
trate was washed with brine and dried over anhydrous
Na2SO4. Removal of the solvent and column chromato-
graphy on silica gel (5:1 PE/EtOAc) gave 20 as two isomers
(the less polar one 149 mg, 0.40 mmol, and the more polar
one 100 mg, 0.27 mmol). Total yield: 83%.
4.1.14. Synthesis of the tricyclic peroxide 8. Hg(OAc)2
(64 mg, 0.20 mmol) and HClO4 (0.61 mL, 0.01 mmol)
were added to a solution of 21 (60 mg, 0.20 mmol) in
CH2Cl2 (2 mL) stirred at ambient temperature. The stirring
was continued at ambient temperature for 1 h. With cooling
(ice-water bath) a freshly prepared solution of NaBH4
(23 mg) in 3 M aq NaOH (0.2 mL) was added. The mixture
was stirred at 0 ꢁC for 1 h. The precipitated Hg black was fil-
tered off. The filtrate was diluted with Et2O, washed with
water and brine, and dried over anhydrous Na2SO4. Removal
of the solvent and column chromatography on silica gel
(10:1 PE/EtOAc) gave 8 as a colorless oil (21 mg,
0.070 mmol, 35% yield from 21): FTIR (film) 2956, 2782,
1739, 1465, 1372, 1284, 1195, 1165, 1070, 1026 cmꢀ1; 1H
NMR (400 MHz, CDCl3) d 4.48–4.40 (m, 1H), 4.16 (q,
J¼7.1 Hz, 2H), 5.35 (dt, J¼12.3, 3.2 Hz, 1H), 3.74 (dd,
J¼11.2, 5.8 Hz, 1H), 2.86 (dd, J¼7.1, 15.2 Hz, 1H), 2.56
(dd, J¼15.3, 9.4 Hz, 1H), 2.21–2.09 (m, 2H), 2.02–1.84
(m, 3H), 1.72–1.69 (m, 1H), 1.54–1.19 (s, 10H), 1.27 (t,
J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 171.2,
104.3, 79.6, 62.1, 60.4, 53.0, 40.8, 36.6, 35.9, 31.1, 28.1,
26.1, 26.0, 23.6, 19.7, 14.2; ESIMS m/z 321.3 ([M+Na]+);
EIHRMS calcd for C16H26O5 (M+) 298.1780, found
298.1791.
Data for the less polar isomer of 20 (colorless oil): FTIR
(film) 1713, 1652, 1452, 1367, 1207, 1160, 1100, 736,
1
698 cmꢀ1; H NMR (400 MHz, CD3COCD3) d 7.33–7.25
(m, 5H), 6.90 (dt, J¼15.6, 6.9 Hz, 1H), 5.80 (d, J¼
15.6 Hz, 1H), 4.47 (s, 2H), 4.12 (q, J¼7.3 Hz, 2H), 3.45 (t,
J¼6.4 Hz, 2H), 2.40–2.37 (m, 2H), 2.22–2.12 (m, 4H),
1.90–1.76 (m, 4H), 1.61–1.55 (m, 2H), 1.30–1.20 (m, 4H),
1.22 (t, J¼7.1 Hz, 3H); 13C NMR (100 MHz, CD3COCD3)
d 212.9, 166.5, 149.7, 140.1, 129.0, 128.2, 128.0, 122.1,
73.1, 71.1, 60.4, 51.3, 50.8, 36.3, 36.2, 30.4, 28.6, 28.2,
26.9, 26.2, 14.6; EIMS m/z (%) 372 (M+, 0.38), 91 (100);
EIHRMScalcdforC23H32O4 (M+) 372.2301, found 372.2295.
Acknowledgements
Data for the more polar isomer of 20 (colorless oil): FTIR
(film) 1717, 1654, 1453, 1367, 1270, 1182, 1101, 1043,
This work was supported by the National Natural
Science Foundation of China (20025207, 20272071,
20372075, 20321202, 20672129, 20621062) and the Chi-
nese Academy of Sciences (‘Knowledge Innovation’ pro-
ject, KJCX2.YW.H08).
1
737, 698 cmꢀ1; H NMR (400 MHz, CD3COCD3) d 7.33–
7.25 (m, 5H), 6.90 (dt, J¼15.6, 6.9 Hz, 1H), 5.81 (d, J¼
15.6 Hz, 1H), 4.47 (s, 2H), 4.12 (q, J¼7.3 Hz, 2H), 3.64 (t,
J¼6.2 Hz, 2H), 2.47–2.40 (m, 2H), 2.20–2.14 (m, 2H),
1.96–1.74 (m, 6H), 1.62–1.42 (m, 6H), 1.22 (t, J¼7.1 Hz,
3H); 13C NMR (100 MHz, CD3COCD3) d 214.8, 166.5,
149.2, 140.1, 129.0, 128.2, 128.0, 122.4, 73.1, 70.7, 60.4,
49.5, 48.5, 33.9, 33.8, 30.5, 29.4, 28.3, 27.9, 21.3, 14.6;
EIMS m/z (%) 372 (M+, 0.26), 327 (M+ꢀOEt, 0.53),
91(100); EIHRMS calcd for C23H32O4 (M+) 372.2301,
found 372.2297.
References and notes
1. See: e.g., (a) Liu, J.-M.; Ni, M.-Y.; Fan, J.-F.; Tu, Y.-Y.; Wu,
Z.-H.; Wu, Y.-L.; Chou, W.-S. Acta Chim. Sin. 1979, 37, 129;
(Chem. Abstr. 1980, 92, 94594w); (b) Li, Y.; Wu, Y.-L. Curr.
Med. Chem. 2003, 10, 2197–2230; (c) Haynes, R. K.;
Vonwiller, S. C. Acc. Chem. Res. 1997, 30, 73–79; (d) O’Neill,
P. M.; Posner, G. H. J. Med. Chem. 2004, 47, 2945–2964; (e)
Robert, A.; Dechy-Cabaret, O.; Cazalles, J. M.; Meunier, B.
Acc. Chem. Res. 2002, 35, 167–174; (f) Klayman, D. L.
Science 1985, 228, 1049–1055; (g) Tang, Y.; Dong, Y.;
Vennerstrom, J. L. Med. Res. Rev. 2004, 24, 425–448; (h) Gu,
H.-M.; Lu, B.-F.; Qu, Z.-X. Acta Pharmacol. Sin. 1980, 1, 48–50.
2. (a) Wu, Y.-K. Acc. Chem. Res. 2002, 35, 255–259; (b) Olliaro,
P. L.; Haynes, R. K.; Meunier, B.; Yuthavong, Y. Trends
Parasitol. 2001, 17, 122–126; (c) Robert, A.; Meunier, B.
4.1.13. Synthesis of hydroxy hemiketal 21 from 20. BCl3
(1 M in CH2Cl2, 2.4 mL, 2.4 mmol) was added dropwise
to a solution of the major (less polar) isomer of 20 obtained
above (219 mg, 0.59 mmol) in dry THF (15 mL) stirred at
ꢀ78 ꢁC under argon. The stirring was continued at the
same temperature for 4 h. The reaction was quenched by ad-
dition of water (5 mL). The mixture was diluted with Et2O,
washed with water and brine, and dried over anhydrous
Na2SO4. Removal of the solvent left a residue, which was