8
916
C. L. L. Chai et al. / Tetrahedron Letters 42 (2001) 8915–8917
OMe OMe
OMe OMe
OMe O
(ii)
(i)
83%
81%
MeO
OMe
MeO
OMe
MeO
OMe
OMe
CHO OMe
(8)
O
(6)
(7)
7
2% (iii)
OMe OMe
OMe OMe
OMe O
R
R'
(iv)
(v)
7
4%
MeO
OMe
MeO
OMe
MeO
OMe
OMe OMe
OMe OMe
OMe O
(
(
(
11) R=R'=Me (79%)
12) R=Et, R'=H (55%)
13) R=Et, R'=Me (95%)
(10)
(9)
(vi)
OH
O
(vii)
R'
R
quant.
(3) R=R'=Me
(4) R=Et, R'=H
5) R=Et, R'=Me
HO
OH
(
OH
O
Scheme 1. Reagents and conditions: (i) excess sodium dithionite, dimethyl sulphate, KOH, NBu Br in water/THF, 18 h; (ii) 5
4
equiv. POCl , 4 equiv. DMF in DCM, 0°C at 30 min then rt for 18 h; (iii) 10-fold excess H O , cat. H SO in MeOH, 90 min
3
2
2
2
4
at rt; (iv) excess sodium dithionite, dimethyl sulphate, KOH, NBu Br in water/THF, 18 h; (v) for (11), 4.5 equiv. BuLi, 4.5 equiv.
4
TMEDA, THF, −78°C, 30 min, then excess MeI, −78°C to rt, 30 min; for (12), 1.2 equiv. BuLi, 1.2 equiv. TMEDA, THF, −78°C,
30 min, then excess EtI, −78°C to rt, 30 min; (vi) 1.2 equiv. BuLi, 1.2 equiv. TMEDA, THF, −78°C, 30 min, then excess MeI,
−
78°C to rt, 30 min; (vii) 5 equiv. BBr , DCM, −78°C to rt, 48 h.
3
Our initial attempts at the C-functionalisation of the
naphthalene 10 utilised organolithium bases (n-BuLi,
tert-BuLi and LICKOR) in the presence of the appro-
priate alkyl halide but no alkylation product was
observed. The presence of tetramethylethylenediamine
the first unambiguous identification of the structure of
boryquinone. Interestingly, boryquinone (5) is also
present in extracts of the cultured mycobiont of
Lecanora hybocarpa (Tuck.) Brodo, and suggests that
this may be the biosynthetic precursor of hybocarpone
3
(
TMEDA) was later found to be crucial to the success
(2), a novel bis-naphthazarin derived pentacycle.
of the alkylation reactions. Hence, treatment of naph-
thalene 10 with 4.5 molar equivalents of n-BuLi and
TMEDA directly gave the naphthalene 11 in 79% yield.
Subsequent demethylation with boron tribromide and
in situ oxidation gave a red solid with identical physical
and spectroscopic properties to aureoquinone (3), a4
new protease inhibitor isolated from Aureobasidium sp.
Acknowledgements
We thank the Australian Research Council for financial
support.
Treatment of naphthalene 10 with 1.2 molar equiva-
lents of n-BuLi, TMEDA and excess ethyl iodide gave
a mixture of starting material: mono-alkylated: dialkyl-
ated products in the ratio of 1:2.7:1.2. The monoalkyl-
ated product 12 was isolated in 55% yield and subse-
quent demethylation followed by aerial oxidation gave
References
1
2
. Thomson, R. H. Naturally Occurring Quinones III. Recent
Advances; Chapman and Hall: London, 1987; pp. 127–343.
. Papageorgiou, V. P.; Assimopoulou, A. N.; Couladouros,
E. A.; Hepworth, D.; Nicolaou, K. C. Angew. Chem., Int.
Ed. 1999, 38, 270–300.
3
-ethyl-2,7-dihydroxynaphthazarin (4), consistent with
5
literature data.
3
. Ernst-Russell, M. A.; Elix, J. A.; Chai, C. L. L.; Willis, A.
C.; Hamada, N.; Nash, T. H., III. Tetrahedron Lett. 1999,
Further alkylation of naphthalene 12 with methyl
iodide and 1.2 molar equivalents of n-BuLi and
TMEDA gave the unsymmetrical naphthalene 13 as
characterised by the NMR spectroscopic data.
Demethylation and aerial oxidation gave the naphthaz-
arin 5. From the physical, spectroscopic and HPLC
analysis, this synthetic sample was found to be identical
in all respects to the naturally occurring naphtho-
quinone boryquinone, detected in extracts from the
40, 6321–6324.
4. Berg, A.; Gorls, H.; Dorfelt, H.; Walther, G.; Schlegel, B.;
Grafe, U. J. Antibiot. 2000, 53, 1293–1295.
5. (a) Moore, R. E.; Singh, H.; Chang, C. W. J.; Scheuer, P.
J. J. Org. Chem. 1966, 31, 3638–3644; (b) Krivoshchekova,
O. E.; Maximov, O. B.; Stepanenko, L. S.; Mishchenko,
N. P. Phytochemistry 1982, 21, 193–196; (c) Stepanenko,
L. S.; Krivoshchekova, O. E.; Dmitrnok, P. S.; Maximov,
O. B. Phytochemistry 1997, 46, 565–568.
6
thallus tips of the lichen Cladonia boryi Tuck. This is