Full Papers
8-Methoxy-b-lapachone (4b): Orange amorphous powder, 62%
yield; H NMR (400 MHz, CDCl3): d=1.46 (6H, s, 2Me), 1.84 (2H, t,
ne A analogues 6a–6c, hydroxyiso-b-lapachones 7a–7c, and sten-
ocarpoquinone B (8a).
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J=6.9 Hz, H-3), 2.55 (2H, t, J=6.9 Hz, H-4), 3.93 (3H, s, OMe), 6.93
(1H, dd, J=2.3 and 8.7 Hz, H-9), 7.27 (1H, d, J=2.3 Hz, H-7),
8.02 ppm (1H, d, J=8.7 Hz H-10); 13C NMR (100 MHz, CDCl3): d=
16.3, 26.8 (2C), 31.7, 55.9, 79.2, 110.5, 113.1, 114.6, 123.6, 131.5,
134.9, 161.2, 165.1, 178.4, 179.2 ppm; IR (film): n˜ =1640, 1589,
1386 cmÀ1; HR EI MS: m/z [M]+ calcd for C16H16O4: 272.1049, found:
272.1043.
Acid conditions: mCPBA (containing 25% H2O, 0.49 mmol) was
added to a solution of lapachols (2a–2c, 0.41 mmol) in CH2Cl2
(10 mL). After stirring for 30 min at RT, various acids were added to
the reaction mixture, and stirring was continued for 1 h. The result-
ing solution was poured into distilled H2O, partitioned with EtOAc,
and washed with saturated aqueous NaHCO3 and brine (with the
use of solid acids, the resulting solution was filtered through Celite
instead of partitioning and washing). Other processes were the
same as with the no-acid conditions.
9-Methoxy-b-lapachone (4c): Orange amorphous powder, 55%
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yield; H NMR (400 MHz, CDCl3): d=1.46 (6H, s, 2Me), 1.84 (2H, t,
J=6.9 Hz, H-3), 2.54 (2H, t, J=6.9 Hz, H-4), 3.90 (3H, s, OMe), 7.12
(1H, dd, J=2.8 and 8.7 Hz, H-8), 7.55 (1H, d, J=3.2 Hz, H-10),
7.71 ppm (1H, d, J=8.7 Hz H-7); 13C NMR (100 MHz, CDCl3): d=
16.1, 26.8 (2C), 31.8, 55.9, 79.3, 110.7, 112.6, 121.0, 125.6, 126.0,
131.8, 161.7, 162.9, 178.7, 180.0 ppm; IR (film): n˜ =1643, 1601,
1391, 1284, 1114 cmÀ1; HR EI MS: m/z [M]+ calcd for C16H16O4:
272.1049, found: 272.1047.
Stenocarpoquinone A (6a): Orange amorphous powder; the yield
is given in Table 1; H NMR (400 MHz, CDCl3): d=1.46 (3H, s, Me),
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1.52 (3H, s, Me), 2.62 (1H, dd, J=5.5 and 18.3 Hz, H-4a), 2.81 (1H,
dd, J=5.5 and 18.3 Hz, H-4b), 3.91 (1H, t, J=5.5 Hz, H-3), 7.51 (1H,
td, J=1.4 and 7.8 Hz, H-8), 7.65 (1H, td, J=1.4 and 7.8 Hz, H-9),
7.84 (1H, dd, J=1.4 and 7.8 Hz, H-7), 8.04 ppm (1H, dd, J=1.4 and
7.8 Hz, H-10); 13C NMR (100 MHz, CDCl3): d=22.2, 25.2, 25.4, 68.3,
81.6, 110.5, 124.5, 128.8, 130.5, 131.0, 132.2, 135.0, 161.7, 178.8,
179.6 ppm; IR (film): n˜ =3373, 1636, 1597, 1570, 1388 cmÀ1; EIMS:
m/z 258 [M]+, 240 [MÀH2O]+, 230 [MÀCO]+; HR EI MS: m/z [M]+
calcd for C15H14O4: 258.0892, found: 258.0881.
Synthesis of dunniones 5a–5c: Dunniols (3a–3c, 0.21 mmol)
were dissolved in CH2Cl2/H2SO4 (1:4, 6 mL) at 08C. After stirring for
1 h, the resulting solution was carefully poured into iced water,
partitioned with CH2Cl2, washed with saturated aqueous NaHCO3
and brine. The organic layer was dried over anhydrous Na2SO4 and
concentrated in vacuo. The residue was purified by silica gel
column chromatography, eluting with EtOAc/n-hexane (1:1) to
yield dunniones 5a–5c.
8-Methoxystenocarpoquinone A (6b): Orange amorphous
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powder; the yield is given in Table 2; H NMR (400 MHz, CDCl3): d=
1.45 (3H, s, Me), 1.51 (3H, s, Me), 2.61 (1H, dd, J=5.0 and 18.3 Hz,
H-4a), 2.80 (1H, dd, J=5.0 and 18.3 Hz, H-4b), 3.92 (1H, t, J=
5.5 Hz, H-3), 3.94 (3H, s, OMe), 6.95 (1H, dd, J=2.8 and 8.7 Hz, H-
9), 7.30 (1H, d, J=2.8 Hz, H-7), 8.05 ppm (1H, d, J=8.7 Hz, H-10);
13C NMR (100 MHz, CDCl3): d=22.2, 25.1, 25.6, 56.0, 68.4, 81.4,
110.8 (2C), 115.0, 123.5, 131.8, 134.4, 160.7, 165.1, 178.1,
179.5 ppm; IR (film): n˜ =3392, 1636, 1582, 1387, 1258 cmÀ1; EIMS:
m/z 288 [M]+, 260 [MÀCO]+; HR EI MS: m/z [M]+ calcd for
C16H16O5: 288.0998, found: 288.0985.
Dunnione (5a): Red amorphous powder, 88% yield; 1H NMR
(400 MHz, CDCl3): d=1.27 (3H, s, Me), 1.46 (3H, s, Me), 1.48 (3H, d,
J=6.9 Hz Me), 4.68 (1H, q, J=6.9 Hz, H-2), 7.54–7.58 (1H, m, H-8),
7.62–7.66 (2H, m, H-6 and H-7), 8.03 ppm (1H, d, J=7.8 Hz, H-9);
13C NMR (100 MHz, CDCl3): d=14.7, 20.4, 25.8, 44.2, 93.0, 123.4,
124.6, 128.0, 129.2, 130.8, 131.7, 134.6, 168.3, 175.5, 181.6 ppm; IR
(film): n˜ =1641, 1601, 1384, 1122 cmÀ1; HR EI MS: m/z [M]+ calcd
for C15H14O3: 242.0943, found: 242.0921.
9-Methoxystenocarpoquinone A
(6c):
Orange
amorphous
7-Methoxydunnione (5b): Red amorphous powder, 49% yield;
1H NMR (400 MHz, CDCl3): d=1.24 (3H, s, Me), 1.42 (3H, s, Me),
1.45 (3H, d, J=6.9 Hz Me), 3.91 (3H, s, OMe), 4.63 (1H, q, J=
6.9 Hz, H-2), 6.96 (1H, dd, J=2.3 and 8.7 Hz,H-8), 7.09 (1H, d, J=
2.8 Hz H-6), 8.00 ppm (1H, d, J=8.7 Hz, H-9); 13C NMR (100 MHz,
CDCl3): d=14.7, 20.4, 25.9, 44.3, 56.0, 92.8, 110.1, 116.2, 123.6,
124.1, 130.2, 132.1, 164.7, 167.5, 176.2, 180.2 ppm; IR (film): n˜ =
1639, 1583, 1384, 1152 cmÀ1; HR EI MS: m/z [M]+ calcd for
C16H16O4: 272.1049, found: 272.1051.
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powder; the yield is given in Table 2; H NMR (400 MHz, CDCl3): d=
1.46 (3H, s, Me), 1.48 (3H, s, Me), 2.43 (1H, dd, J=5.0 and 17.4 Hz,
H-4a), 2.71 (1H, dd, J=5.0 and 17.4 Hz, H-4b), 3.93 (3H, s, OMe),
4.30 (1H, t, J=5.5 Hz, H-3), 7.27 (1H, dd, J=2.7 and 8.7 Hz, H-8),
7.45 (1H, d, J=2.8 Hz, H-10), 7.79 ppm (1H, d, J=8.7 Hz, H-7);
13C NMR (100 MHz, CDCl3): d=21.3, 25.2, 25.3, 55.9, 68.2, 81.9,
109.7, 113.1, 120.6, 125.7, 126.5, 132.4, 161.5, 162.2, 178.8,
179.8 ppm; IR (film): n˜ =3394, 1643, 1603, 1562, 1391, 1287 cmÀ1
;
EIMS: m/z 288 [M]+, 260 [MÀCO]+; HR EI MS: m/z [M]+ calcd for
8-Methoxydunnione (5c): Red amorphous powder, 40% yield;
1H NMR (400 MHz, CDCl3): d=1.26 (3H, s, Me), 1.44 (3H, s, Me),
1.46 (3H, d, J=6.4 Hz Me), 3.91 (3H, s, OMe), 4.64 (1H, q, J=
6.9 Hz, H-2), 7.10 (1H, dd, J=2.8 and 8.7 Hz, H-7), 7.54–7.57 ppm
(2H, m, H-6 and H-9); 13C NMR (100 MHz, CDCl3): d=14.7, 20.5,
25.9, 44.0, 56.0, 92.9, 114.2, 120.2, 120.6, 121.3, 126.3, 132.8, 162.7,
C16H16O5: 288.0998, found: 288.0995.
Hydroxyiso-b-lapachone (7a): Red amorphous powder; the yield
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is given in Table 1; H NMR (400 MHz, CDCl3): d=1.26 (3H, s, Me),
1.39 (3H, s, Me), 3.05 (2H, dd, J=1.8 and 11.0 Hz, H-3), 4.90 (1H, t,
J=9.6 Hz, H-2), 7.51–7.63 (3H, m, H-6, H-7, and H-8), 8.00 ppm (1H,
d, J=8.2 Hz, H-9); 13C NMR (100 MHz, CDCl3): d=24.5, 25.9, 27.5,
71.8, 93.6, 116.1, 124.6, 127.4, 129.6, 130.7, 132.1, 134.7, 169.9,
175.4, 181.1 ppm; IR (film): n˜ =3409, 1649, 1610, 1492, 1367 cmÀ1
HR EI MS: m/z [M]+ calcd for C15H14O4: 258.0892, found: 258.0865.
169.1, 175.4, 181.8 ppm; IR (film): n˜ =1645, 1604, 1402, 1281 cmÀ1
;
HR EI MS: m/z [M]+ calcd for C16H16O4: 272.1049, found: 272.1019.
;
Synthesis of stenocarpoquinone A analogues 6a–6c, hydroxyi-
so-b-lapachone analogues 7a–7c, and stenocarpoquinone B
(8a): No-acid conditions: mCPBA (containing 25% H2O) was added
to a solution of lapachols (2a–2c, 0.41 mmol) in CH2Cl2 (10 mL).
After stirring for 1.5 h at RT, the resulting solution was poured into
distilled H2O, partitioned with EtOAc, washed with brine. The or-
ganic layer was dried over anhydrous Na2SO4 and concentrated in
vacuo. The residue was purified by silica gel column chromatogra-
phy, eluting with EtOAc/n-hexane (1:1) to yield stenocarpoquino-
7-Methoxyhydroxyiso-b-lapachone (7b): Red amorphous powder;
the yield is given in Table 2; 1H NMR (400 MHz, CDCl3): d=1.28
(3H, s, Me), 1.41 (3H, s, Me), 3.08 (2H, dd, J=1.4 and 7.3 Hz, H-3),
3.94 (3H, s, OMe), 4.91 (1H, t, J=8.7 Hz, H-2), 6.99 (1H, dd, J=2.8
and 8.7 Hz, H-8), 7.12 (1H, d, J=2.8 Hz, H-6), 8.05 ppm (1H, d, J=
8.7 Hz, H-9); 13C NMR (100 MHz, CDCl3): d=24.3, 25.9, 27.7, 56.1,
71.9, 93.4, 110.7, 115.9, 116.3, 123.9, 129.5, 132.5, 164.7, 169.1,
ChemMedChem 2015, 10, 1413 – 1423
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