Flexible Route to Palmarumycin CP1 and CP2 and CJ-12.371 Methyl Ether
3Ј, C-5Ј), 122.4 (d, C-4), 122.6 (d, C-5), 125.5 (d, C-3), 127.7 (d, moved at reduced pressure, and the residue was purified by column
C-6), 136.9 (s, C-4a), 144.2 (s, C-1Ј), 146.1 (s, C-1), 154.1 (s, C-4Ј),
156.4 (s, C-8) ppm.
chromatography over silica gel (DCM) to afford palmarumy-
cin CP1 methyl ether 16 (1.41 g, 95%). M.p. 203–204 °C (ref.[31]
m.p. 204 °C). 1H NMR (500 MHz, CDCl3): δ = 3.99 (s, 3 H,
OCH3), 6.28 (d, J = 10.5 Hz, 1 H, 3-H), 6.85 (d, J = 10.5 Hz, 1 H,
2-H), 6.97 (d, J = 7.6, Hz, 2 H, 2Ј-H, 7Ј-H), 7.17 (d, J = 8.5 Hz, 1
H, 6-H), 7.46 (t, J = 7.5 Hz, 2 H, 3Ј-H, 6Ј-H), 7.56 (d, J = 8.4 Hz,
2 H, 4Ј-H, 5Ј-H), 7.59 (d, J = 7.7 Hz, 1 H, 8-H), 7.70 (t, J = 8.2 Hz,
1 H, 7-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 56.4 (q, OCH3),
93.4 (s, C-1), 109.8 (d, C-2Ј, C-7Ј), 113.55 (d, C-8aЈ), 114.2 (s, C-
6), 119.0 (s, C-4a), 120.2 (d, C-8), 121.2 (s, C-4Ј, C-5Ј), 127.6 (d,
C-3Ј, C-6Ј), 132.2 (d, C-3), 134.2 (s, C-4aЈ), 134.9 (d, C-7), 135.2
(d, C-2), 141.1 (s, C-8a), 147.4 (s, C-1Ј, C-8Ј), 159.9 (s, C-5), 182.9
(s, C-4) ppm.
Benzoquinone Acetal (10)
Oxidation with Active MnO2 (Method A): A solution of 1-(4Ј-ami-
nophenyloxy)-8-naphthol (14; 10.05 g, 0.04 mol) in dry toluene
(100 mL) was treated with active manganese dioxide (17.40 g,
0.20 mol), and the mixture was stirred overnight at room tempera-
ture under an atmosphere of argon. The suspension was filtered,
the toluene was removed at reduced pressure, and the residue was
purified by silica gel chromatography to yield benzoquinone acetal
10 as faintly yellow crystals (7.50 g, 75%, ref.[39] 70–80%). M.p.
1
115 °C. H NMR (500 MHz, CDCl3): δ = 6.33 (d, J = 10.3 Hz, 2
H, 3-H, 5-H), 6.96 (d, J = 10.3 Hz, 2 H, 2-H, 6-H), 6.98 (dd, J =
8.0, 1.5 Hz, 2 H, 2Ј-H, 7Ј-H), 7.46 (dd, J = 8.0, 1.5 Hz, 2 H, 4Ј-H,
5Ј-H) 7.56 (t, J = 8.0 Hz, 2 H, 3Ј-H, 6Ј-H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 92.0 (s, C-1), 109.7 (d, C-2Ј, C-7Ј), 113.1
(s, C-4aЈ), 121.3 (d, C-4Ј, C-5Ј), 127.9 (d, C-3Ј, C-6Ј), 129.9 (d, C-
3, C-5), 134.1 (s, C-8aЈ), 140.1 (d, C-2, C-6), 146.4 (d, C-1Ј, C-8Ј),
184.5 (s, C-4) ppm.
5-Hydroxyspiro[naphthalene-1,2Ј-naphtho[1,8-de][1,3]dioxin]-4-one,
Palmarumycin CP1 (4): A solution of methyl ether 16 (330 mg,
1.0 mmol) in dry DCM (5 mL) was treated dropwise at –78 °C un-
der an atmosphere of nitrogen with a solution of BBr3 (1.0 in
DCM, 1.91 mL). During the addition, the color of the solution
turned from slightly yellow to red. The solution was warmed to
–30 °C and water (15 mL) was added, and the mixture was stirred
for 5 h. The mixture was extracted with DCM (3ϫ15 mL), the or-
ganic phase was dried with MgSO4, and the solvent was removed
at reduced pressure to yield 4 (300 mg, 95%). M.p. 171–172 °C.
The data of the synthetic product were identical to those of the
natural product.[11,31]
Oxidation of Bisphenol 9 with Silver Oxide (Method B): A similar
oxidation of 9 with silver oxide afforded 64% of benzoquinone
acetal 10.
Oxidation with PIDA (Method C): The oxidation of 14 (1.00 g,
4.00 mmol) in dry dichloromethane (30 mL) with phenyliodine di-
acetate (PIDA; 1.93 g, 6.00 mmol) at room temperature under an
atmosphere of argon afforded 10 (0.23 g, 23%) after chromato-
graphic purification.
CJ-12.371 Methyl Ether (17): A solution of 16 (102 mg, 0.31 mmol)
in ethyl acetate (7.0 mL) was treated with Pd/C (10%, 30 mg), and
the suspension was stirred under hydrogen (atmospheric pressure)
for 12 h. The catalyst was filtered off, the solvent was removed
under reduced pressure, and the residue was purified by flash
chromatography over silica gel (3.0 g) to afford 17[8] methyl ether
5-Methoxy-4a,5,8,8a-pentahydrospiro[naphthalene-1,2Ј-naphtho[1,8-
de][1,3]dioxin]-4-one (15): A suspension of benzoquinone acetal 10
(2.50 g, 0.01 mol) in 1-methoxy-1,3-butadiene (4.20 g, 0.05 mmol)
was stirred under an atmosphere of argon at room temperature for
4–5 d (TLC monitoring). After completion of the reaction, the ex-
cess amount of 1-methoxy-1,3-butadiene was evaporated under
high vacuum, and the residue was filtered through a pad of silica
gel to afford white crystals of Diels–Alder mono adduct 15 (3.17 g,
(83 mg, 81%) as a resin. IR (KBr): ν = 3534, 3053, 2929, 2836,
˜
1765, 1615, 1589, 1460, 1413, 1377, 1258, 1062, 963, 824, 767 cm–1.
UV (MeOH): λ (log ε) = 327 (3.64), 313 (3.79), 300 (3.92), 286
1
(3.90) nm. H NMR (200 MHz, CDCl3): δ = 2.39 (t, J = 8.0 Hz, 1
H, 2-H), 2.10 (t, J = 8.0 Hz, 1 H, 3-H), 3.07 (m, 1 H, 4-H), 5.10
(s, 1 H, 4-OH), 6.93 (d, J = 7.8 Hz, 1 H, 6-H), 7.48 (t, J = 7.8 Hz,
1 H, 7-H), 7.44 (d, J = 7.8 Hz, 1 H, 8-H), 7.03 (dd, J = 8.1, 1.5 Hz,
2 H, 2Ј-H, 7Ј-H), 7.56 (t, J = 8.1 Hz, 2 H, 3Ј-H, 6Ј-H), 7.50 (dd, J
= 8.1, 1.5 Hz, 2 H, 4Ј-H, 5Ј-H) ppm. 13C NMR (50 MHz, CDCl3):
δ = 100.46 (C-1), 26.78 (C-2), 26.27 (C-3), 63.15 (C-4), 129.91 (C-
4a), 157.57 (C-5), 111.76 (C-6), 128.27 (C-7), 119.84 (C-8), 134.60
(C-8a), 148.44 (C-1Ј), 109.86 (C-2Ј), 127.89 (C-3Ј), 120.83 (C-4Ј),
136.63 (C-4aЈ), 126.76 (C-5Ј), 127.77 (C-6Ј), 109.67 (C-7Ј), 148.36
(C-8Ј), 114.04 (C-8aЈ) ppm. MS (EI): m/z (%) = 334 (42) [M]+, 316
(100), 311 (45), 284 (21), 256 (8), 221 (35), 178 (18), 115 (31), 84
(78). HRMS (EI): calcd. for C21H18O4 [M]+ 334.1205; found
334.1204.
95%). M.p. 143–144 °C. IR (KBr): ν = 3418, 3059, 2977, 2923,
˜
2819, 1694, 1634, 1607, 1585, 1520, 1416, 1378, 1275, 1183, 1117,
824, 758 cm–1. UV (MeOH): λ (logε) = 327 (3.55), 312 (3.68), 301
1
(3.78), 297 (3.77) nm. H NMR (500 MHz, CDCl3): δ = 2.27 (m,
1 H, 8-H), 2.39 (m, 1 H, 8-H), 2.97 (m, 1 H, 8a-H), 3.46 (s, 3 H,
OCH3), 3.68 (m, 1 H, 4a-H), 4.13 (m, 1 H, 5-H), 6.19 (d, J =
11.0 Hz, 1 H, 6-H), 6.25 (m, 1 H, 7-H), 6.34 (d, J = 10.0 Hz, 1 H,
3-H), 6.79 (d, J = 10.0 Hz, 1 H, 2-H), 6.87 (dd, J = 10.0, 3.0 Hz,
2 H, 2Ј-H, 7Ј-H), 7.54 (t, J = 8.1 Hz, 2 H, 3Ј-H, 6Ј-H), 7.53 (d, J
= 8.1 Hz, 2 H, 4Ј-H, 5Ј-H) ppm. 13C NMR (125 MHz, CDCl3): δ
= 24.4 (t, C-8), 42.2 (d, C-8a), 45.3 (d, C-4a), 57.0 (q, OCH3), 77.3
(s, C-5), 99.9 (s, C-1), 109.6 (d, C-7Ј), 110.1 (d, C-2Ј), 113.7 (s, C-
8aЈ), 121.3 (d, C-5Ј), 121.5 (d, C-4Ј), 125.4 (d, C-3), 127.9 (d, C-3Ј,
C-6Ј), 128.8 (d, C-7), 132.2 (d, C-6), 134.6 (s, C-4aЈ), 138.7 (d, C-
2), 146.7 (s, C-8Ј), 147.5 (s, C-1Ј), 196.4 (s, C-4) ppm. MS (EI): m/z
(%) = 334 (55) [M]+, 319 (2), 302 (3), 263 (5), 247 (5), 197 (58), 196
(13), 159 (18), 115 (62), 105 (105), 71 (21), 57 (11), 28 (100).
C21H18O4 (334.371): calcd. C 75.37, H 5.42; found C 74.64, H 5.18.
5-Hydroxyspiro[naphthalene-1,2Ј-naphtho[1,8-de][1,3]dioxin]-2,3-
dihydro-4-one (18): A solution of 17 (75 mg, 0.22 mmol) in dry
DCM (2.0 mL) was treated with pyridinium chlorochromate
(119 mg, 0.55 mmol) at room temperature. The mixture was stirred
until the starting material was consumed (TLC monitoring). The
solvent was removed under reduced pressure, and the resulting resi-
due was purified by flash chromatography over silica gel (3.6 g;
hexane/ethyl acetate, 95:5Ǟ8:2) to afford ketone 18 (palmarumy-
cin CP2 methyl ether; 64 mg, 86%) as yellow crystals. M.p 153–
155 °C (ref.[31] m.p. 154–156 °C). 1H NMR (200 MHz, CDCl3): δ
= 2.51 (t, J = 8.0 Hz, 1 H, 2-H), 2.81 (t, J = 8.0 Hz, 1 H, 2-H),
7.16 (dd, J = 8.0, 1.7 Hz, 1 H, 6-H), 7.68 (t, J = 8.0 Hz, 1 H, 7-
H), 7.44 (dd, J = 8.0, 1.7 Hz, 1 H, 8-H), 6.98 (dd, J = 7.5, 2.0 Hz,
5-Methoxyspiro[naphthalene-1,2Ј-naphtho[1,8-de][1,3]dioxin]-4-one
(16): A solution of Diels–Alder adduct 15 (1.50 g, 4.49 mmol) in
dry toluene (20 mL) was treated under an atmosphere of nitrogen
with DDQ (1.52 g, 6.73 mmol). The reaction mixture was stirred
for 24 h at 85 °C [TLC monitoring, dichloromethane (DCM)]. Af-
ter cooling, the reaction mixture was filtered, the solvent was re-
Eur. J. Org. Chem. 2010, 4476–4481
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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