D. Mal et al. / Tetrahedron Letters 45 (2004) 7895–7898
7897
CH3
with naphthoquinone monoketal 24, the corresponding
product 25b was also obtained in excellent yield. Acid
assisted deketalization of 25 correspondingly provided
26 having all the important structural components of
the hayumicin18 (3) aglycon.
COOMe
CH3
OH
CH3
COOMe
CHO
COOMe
c
a, b
O
O
NH2
20
19
18
OMe
CN
O
In conclusion, a novel extension of the Hauser–Kraus
annulation has been utilized for the one-pot regiospecific
synthesis of three different categories (i.e., 12, 22 and 26)
of benzonaphthopyranones from readily accessible
starting materials. The methodology has been success-
fully applied to a concise total synthesis of chartarin
22b and the first entry to the chrymutasin scaffold 26
through hitherto unknown and structurally unique
benz[a]anthraquinone monoketals 25. Work is in pro-
gress towards the completion of the total synthesis of
aglycons of chrymutasins and gilvocarcins. It is foresee-
able that the present methodology would be able to gen-
erate a large number of useful benzonaphthopyranones.
O
CH3
OR
O
22a R = CH3
22b R = H
d,
21
e
O
O
OH
O
Scheme 3. Total synthesis of chartarin. Reagents and conditions: (a) i.
5.4vol% H2SO4, NaNO2, 0°C, ii. D (66%); (b) (CH2)6N4, PPA, D
(30%); (c) Ph3P@CHCOOEt, Et2NPh,
ꢀ60°C ! rt (86%); (e) HBr, AcOH, D (81%).
D
(95%); (d) LiOtBu,
quite apprehensive that the reaction between 13 and the
required naphthoquinone monoketal 24, prepared from
methyl 6-hydroxynaphthoate 23 might lead to the for-
mation of hydroxymethoxyanthraquinone 27, in accord-
ance with our reported results.13 It may also be
noted that in an earlier investigation of ours, the naph-
thoquinone monoketal 24 desisted from undergoing
annulation with phthalide sulfone. Gratifyingly, cyano-
phthalide 13 underwent smooth annulation with
Michael acceptor 24 giving the desired product 25a in
an excellent yield (Scheme 4). When methoxy substi-
tuted cyanophthalide 21 was submitted to annulation
Acknowledgements
We are grateful to CSIR, New Delhi for financial sup-
port of this work. A.P. gratefully acknowledges the
receipt of a Senior Research Fellowship from CSIR,
New Delhi. Dr. Samik Nanda of Texas A & M and
Dr. Dipanjan Pan of Washington University provided
some spectral data.
References and notes
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OMe
CN
MeOOC
MeOOC
O
b,
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O
a
OMe
OMe
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OH
23
O
24
O
O
R
O
R
O
O
c
OMe
OMe
O
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OH
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OH
25a R = H
25b R = OMe
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26b R = OMe
MeOOC
O
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OMe
O
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27
Scheme 4. Synthesis of chrymutasin and hayumicin skeletons. Rea-
gents and conditions: (a) PIDA (2equiv), CH3OH, 0°C (68%); (b)
LiOtBu, ꢀ60°C ! rt (87%); (c) aq HCl, MeOH (98%); PIDA = phe-
nyliodonium diacetate.