Synthesis of Dehydro-a-Lapachone and a-Lapachone
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for analytical TLC. Flash column chromatography was performed using
silica gel 9385 (Merck). Melting points were determined in capillary tubes on
a Fisher-Johns apparatus and are uncorrected. 1H NMR spectra were
recorded on a Bruker Model ARX (300 MHz) spectrometer. IR spectra were
recorded on a Jasco FTIR 5300 spectrophotometer. HRMS mass spectra
were carried out by Korea Basic Science Institute (Daegu).
Dehydro-a-lapachone (3). Method A: the 2-hydroxy-1,4-naphthoquinone
(7) (174mg, 1 mmol) and 3-methyl-2-butenal (168mg, 2 mmol) were dissolved
in DMF (5 mL), and Yb(OTf)3 (62 mg, 1 mmol) was added at room temperature.
The mixture was stirred at 1008C for 5 h and then cooled to room temperature.
Removal of solvent at reduced pressure left an oily residue, which was then
purified by column chromatography on silica gel to give 3 (132mg, 55%) as a
solid: mp 145–1468C (lit. 1488C[1e]); 1H NMR (300MHz, CDCl3) d
8.11–8.05 (2H, m), 7.70–7.64 (2H, m), 6.64 (1H, d, J ¼ 10.0Hz), 5.71 (1H,
d, J ¼ 10.0Hz), 1.54 (6H, s); IR (KBr) 3079, 3017, 2976, 2922, 1676, 1647,
1593, 1570, 1416, 1331, 1275, 1211, 1190, 1134, 968, 947 cm21
.
Method B: the 2-hydroxy-1,4-naphthoquinone (7) (1.740 g, 10 mmol)
and 3-methyl-2-butenal (1.680 mg, 20 mmol) were dissolved in MeOH
(40 mL), and ethylenediamine diacetate (180 mg, 1 mmol) was added at
room temperature. The mixture was stirred at room temperature for 5 h.
Removal of solvent at reduced pressure left an oily residue, which was then
purified by column chromatography on silica gel to give 3 (1.802 g, 75%)
as a solid.
2,2-Dimethyl-3,4,6,7,8,9-hexahydro-2H-benzo[g]chromene-5,10-dione
(10). To synthetic material 3 (200 mg, 0.84 mmol) in a Parr bottle in EtOAc
(10 mL) was added 10% Pd/C (20 mg). The bottle was shaken for 1 h at
40 psi H2. Removal of solvent at reduced pressure left an oily residue, which
was then purified by column chromatography on silica gel to give 10
1
(198 mg, 97%) as a solid: mp 153–1558C; H NMR (300 MHz, CDCl3) d
2.44–2.35 (6H, m), 1.70 (2H, t, J ¼ 6.6 Hz), 1.67–1.63 (4H, m), 1.35 (6H,
s); IR (KBr) 2943, 1667, 1649, 1630, 1609, 1456, 1397, 1362, 1298, 1275,
1221, 1159, 1117, 936 cm21; HRMS m/z (Mþ) Calcd. for C15H18O3,
246.1256. Found 246.1258.
a-Lapachone (1). To synthetic material 3 (300 mg, 1.25 mmol) in a Parr
bottle in EtOAc (10 mL) was added 10% Pd/C (20 mg). The bottle was shaken
for 20 min at 10 psi H2. Removal of solvent at reduced pressure left an
oily residue, which was then purified by column chromatography on silica
gel to give 1 (299 mg, 99%) as a solid: mp 113–1148C (lit. 1168C,[1e]);
1H NMR (300 MHz, CDCl3) d 8.08–8.02 (2H, m), 7.70–7.62 (2H, m), 2.60
(2H, t, J ¼ 6.6 Hz), 1.80 (2H, t, J ¼ 6.6 Hz), 1.42 (6H, s); IR (KBr)
2974, 2948, 1682, 1638, 1613, 1578, 1391, 1341, 1310, 1273, 1208, 1119,
961 cm21
.