Asymmetric diastereoselective syntheses of the aphid insect pigment derivatives quinone A and quinone A′

Article abstract of DOI:10.1016/S0040-4039(01)00955-8

Commercially available (R)-lactate has been used to provide the chiral source for the asymmetric diastereoselective syntheses of all four stereoisomers of 3,4-dihydro-4,7,9-trihydroxy-1,3-dimethylnaphtho[2,3-c]pyran-5,10-quinone based on 3R stereochemistr

Full text of DOI:10.1016/S0040-4039(01)00955-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5753–5754
Asymmetric diastereoselective syntheses of the aphid insect
pigment derivatives quinone A and quinone A%
Robin G. F. Giles,a,* Ivan R. Green,b Francois J. Oosthuizena and C. Peter Taylora
aDepartment of Chemistry, Murdoch University, Murdoch, WA 6150, Australia
bDepartment of Chemistry, University of the Western Cape, Bellville 7530, South Africa
Received 17 April 2001; accepted 1 June 2001
Abstract—Commercially available (R)-lactate has been used to provide the chiral source for the asymmetric diastereoselective
syntheses of all four stereoisomers of 3,4-dihydro-4,7,9-trihydroxy-1,3-dimethylnaphtho[2,3-c]pyran-5,10-quinone based on 3R
stereochemistry. The (1R,3R,4S) and (1R,3R,4R) stereoisomers were identical with the natural derivatives of the aphid insect
pigments quinone A and quinone A%, while the (1S,3R,4S) and (1S,3R,4R) stereoisomers were found to be the enantiomers of two
hitherto unreported naturally derived quinones from alternative aphid insect sources. A key-step is the titanium tetraisopropoxide-
induced intramolecular diastereoselective cyclization of meta-hydroxybenzyl protected lactaldehydes to afford benzo[c]pyran-4,5-
diols. © 2001 Elsevier Science Ltd. All rights reserved.
The quinones A 1 and A% 2 are a pair of C-4 epimeric
naphthopyranols derived through reduction of the bean
and willow aphid insect pigments protoaphin-fb and
protoaphin-sl, respectively.1 These quinones have been
synthesized previously in racemic form;2 we now
describe their first diastereoselective asymmetric synthe-
ses, together with those of their C-1 epimers 3 and 4.
These comprise all four stereoisomers based on 3R
stereochemistry. Following the completion of these four
syntheses, discussions with Professor Cameron revealed
that compounds 3 and 4 are the enantiomers of two
further, unreported, derivatives of naturally occurring
aphid pigments.3
diastereomer using titanium tetraisopropoxide.5,6
Debenzylation7 of 7 through hydrogenolysis followed
by immediate oxidation of the intermediate
hydroquinone 8 with cerium(IV) ammonium nitrate
gave the quinone 16 in 41% overall yield for the two
steps. The benzopyranquinone 17, the C-4 epimer of 16,
was obtained through methylation of the phenolic ben-
zopyran 7 to afford the methyl ether 9. The C-4 pseudo-
equatorial stereochemistry of this alcohol was reversed
through treatment of 9 with phosphorus pentachloride
followed by silver nitrate in aqueous acetonitrile2
to afford the epimeric C-4 pseudoaxial alcohol 10 in
87% from diol 7. Debenzylation7 of 10 followed by
cerium(IV) ammonium nitrate oxidation of the prod-
uct 11 afforded the target benzopyranquinone 17 in 50%
overall yield.
The related cyclization of the benzyl-epimeric aldehyde
6 yielded a mixture of the C-4 epimeric benzopyrans 12
(51%) and 13 (30%). Each of these was individually
debenzylated7 to afford the intermediate hydroquinones
14 and 15, respectively, and these were oxidized as
before to give the separate benzopyranquinones 18 and
19 in overall yields of 43 and 42% respectively.
The enantiopure phenolic aldehyde 54 was cyclized in
69% yield to afford the benzopyran 7 as a single
In Diels–Alder reactions in which bromine controlled
the regiochemistry,8 each of the quinones 16–19 was
separately treated with 1-methoxy-1,3-trimethylsilyloxy-
1,3-butadiene,9 from which each of the naphthopyran-
quinones 1–410 was obtained in yields of 20–30%.
Keywords: asymmetric syntheses; naphthopyranquinones; intramolec-
ular diastereoselective cyclizations.
* Corresponding author. Fax: +61
8 9310 1711; e-mail: r.giles
@murdoch.edu.au
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00955-8

5754
R. G. F. Giles et al. / Tetrahedron Letters 42 (2001) 5753–5754
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