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DOI: 10.1055/s-0029-1218578
Synthesis of the Reported Structure of Crassiflorone, a Pentacyclic Naphthoquinone Isolated from the African Ebony Diospyros crassiflora
Publication History
Publication Date:
17 December 2009 (online)
Abstract
A short synthesis of the furocoumarin naphthoquinone structure reported for the natural product crassiflorone is described, in which the key steps are a Diels-Alder reaction to form 2-bromo-8-hydroxy-6-methylnaphthoquinone, followed by O-protection and copper(II)-mediated coupling to 4-hydroxy-5-methylcoumarin to establish the pentacyclic framework.
Key words
quinones - natural products - fused ring systems - Diels-Alder reaction - copper
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References and Notes
11-Benzyloxy-1,9-dimethyl-6
H
-naphtho[2′,3′:4,5]furo[3,2-
c
]-chromene-6,7,12-trione
(6)
To a mixture of 2-bromo-8-benzyloxy-6-methyl-1,4-naphthoquinone
(4, 0.20 g, 0.56 mmol), Cu(OAc)2 (0.30
g, 1.67 mmol), 4-hydroxy-5-methylcoumarin (3,
0.10 g, 1.67 mmol), and K2CO3 (0.20 g, 1.67
mmol) was added MeCN (10 mL). The reaction mixture was heated to
reflux for 8 h with constant stirring. After 8 h, the mixture was
diluted with CH2Cl2 (100 mL), and filtered
through Celite, washing with CH2Cl2-MeOH
(9:1; 100 mL). The filtrate was concentrated under reduced pressure,
and the residue was purified by flash column chromatography to give
the title compound (0.14 g, 56%); mp 236-238 ˚C.
HRMS: m/z calcd for C28H18O6 + Na+:
473.0996; found: 473.0985 [M + Na+].
IR (CHCl3): νmax = 2985,
1731, 1446, 1374, 1249, 1045 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 7.71 (1 H,
s, ArH), 7.62 (2 H, d, J = 7.4
Hz, ArH), 7.52 (1 H, dd, J = 8.0,
7.8 Hz, ArH), 7.42 (2 H, dd, J = 7.4,
7.8 Hz, ArH), 7.33 (2 H, d, J = 7.6
Hz, ArH), 7.22 (1 H, d, J = 7.5
Hz, ArH), 7.18 (1 H, s, ArH), 5.28 (2 H, s, CH2), 2.94
(3 H, s, Me), 2.50 (3 H, s, Me). ¹³C
NMR (100 MHz, CDCl3): δ = 177.9 (C),
172.2 (C), 162.0 (C), 159.8 (C), 155.2 (C), 154.9 (C), 154.3 (C),
147.4 (C), 136.0 (C), 135.9 (C), 136.6 (C), 132.5 (CH), 128.7 (CH),
127.9 (CH), 127.1 (CH), 126.7 (CH), 124.2 (C), 121.9 (C), 120.1
(CH), 117.2 (C), 115.2 (CH), 110.7 (C), 107.3 (C), 70.8 (CH2), 22.5
(Me), 21.5 (Me).
11-Hydroxy-1,9-dimethyl-6
H
-naphtho[2′,3′:4,5]furo[3,2-
c
]-chromene-6,7,12-trione
(1, ‘crassiflorone’)
The benzyl
ether 6 (0.10 g,) was dissolved in EtOAc
(10 mL), and Pearlman’s catalyst (20 mg) was added. The reaction
mixture was flushed carefully with nitrogen followed by hydrogen,
then stirred for 16 h under a hydrogen atmosphere. The reaction
mixture was filtered through Celite, washing with 5% MeOH
in CH2Cl2 (100 mL). The filtrate was concentrated
under reduced pressure, and the residue was subjected to silica
gel chromatography to give the title compound (0.09 g, 93%);
mp 230 ˚C (decomp.). HRMS: m/z calcd
for C21H12O6 + H+:
361.0707; found: 361.0700 [M + H+]; m/z calcd for C21H12O6 + Na+:
383.0526; found: 383.0537 [M + Na+].
IR (CHCl3): νmax = 3689,
3604, 3043, 1755, 1644, 1603, 1239 cm-¹.
UV/Vis (MeOH):
λmax = 305
(log ε 4.056), 440 (log ε 3.54) nm. ¹H
NMR (400 MHz; CDCl3): δ = 11.84 (1
H, s, 11-OH), 7.66 (1 H, s, H-8), 7.58 (1 H, dd, J = 8.2,
7.6 Hz, H-3), 7.38 (1 H, d, J = 8.2
Hz, H-4), 7.26 (1 H, d, J = 7.6
Hz, H-2), 7.14 (1 H, s, H-10), 2.96 (3 H, s, Me-14), 2.51 (3 H,
s, Me-15). ¹³C NMR (125 MHz; CDCl3): δ = 177.7
(C), 177.3 (C), 162.83 (C), 162.80 (C), 155.1 (C), 154.7 (C), 152.9
(C), 149.4 (C), 136.0 (C), 133.2 (C), 133.1 (CH), 127.3 (CH), 127.2
(C), 124.7 (CH), 122.5 (CH), 115.4 (CH), 112.4 (C), 110.5 (C), 107.9
(C), 22.4 (Me), 21.4 (Me).
Crystallographic data (reference number
CCDC 75266) can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or
from the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge, CB21EZ, UK;
fax: +44 (1223)336033;
or deposit@ccdc.cam.ac.uk].