Synthesis of the reported structure of the bisbenzoquinone lanciaquinone, isolated from Maesa lanceolata

Article abstract of DOI:10.1021/ol801697g

(Chemical Equation Presented) Lanciaquinone, isolated from Maesa lanceolate, was originally assigned as a bisbenzoquinone with a C ¹⁴-chain linking the two quinone rings. A synthesis of the reported structure, in which the key step is a double Clalsen rearrangement, suggests that the structure of the natural product needs to be revised.

Full text of DOI:10.1021/ol801697g

ORGANIC
LETTERS
2008
Vol. 10, No. 20
4505-4508
Synthesis of the Reported Structure of
the Bisbenzoquinone Lanciaquinone,
Isolated from Maesa lanceolata
Loic Guillonneau, David Taddei, and Christopher J. Moody*
School of Chemistry, UniVersity of Nottingham, UniVersity Park,
Nottingham NG7 2RD, United Kingdom
c.j.moody@nottingham.ac.uk
Received July 26, 2008
ABSTRACT
Lanciaquinone, isolated from Maesa lanceolata, was originally assigned as a bisbenzoquinone with a C14-chain linking the two quinone rings.
A synthesis of the reported structure, in which the key step is a double Claisen rearrangement, suggests that the structure of the natural
product needs to be revised.
Quinones are ubiquitous in Nature and often participate in
important biological redox processes such as in the electron
transport pathways in photosynthesis that occur in the
chloroplast of green plants.1-3 Plants and trees of the
Myrsinaceae family comprise 35 genera and over 1000
species and are a rich source of natural products, including,
not surprisingly, quinones. One of the more unusual groups
of compounds is the ardisiaquinones in which two benzo-
quinones are linked by a long hydrocarbon chain as in the
symmetrical ardisiaquinone A 1.4,5 Recently, another bis-
benzoquinone derivative, lanciaquinone, was isolated from
a Myrsinaceae species, Maesa lanceolata, and assigned the
unusual structure 2 in which the two quinones are linked by
a C14-alkyl chain (Figure 1).6 In continuation of our interest
in naturally occurring quinones,7-9 we were intrigued by the
(1) Thomson, R. H. Naturally Occurring Quinones, 2nd ed.; Academic
Press: London, 1971
(2) Thomson, R. H. Naturally Occurring Quinones III. Recent adVances,
3rd ed.; Chapman and Hall: London, 1987
(3) Thomson, R. H. Naturally Occurring Quinones IV. Recent adVances,
4th ed.; Blackie: London, 1997
(4) Ogawa, H.; Natori, S. Chem. Pharm. Bull. 1968, 16, 1709–1720
(5) Yang, L. K.; Khoo-Beattie, C.; Goh, K. L.; Chng, B. L.; Yoganathan,
K.; Lai, Y. H.; Butler, M. S. Phytochemistry 2001, 58, 1235–1238
.
Figure 1. Structures of the naturally occurring bisbenzoquinones,
.
ardisiaquinone A and lanciaquinone.
.
.
structure of lanciaquinone 2, even more so when we
examined the data for the natural product. For example, the
.
10.1021/ol801697g CCC: $40.75
Published on Web 09/12/2008
2008 American Chemical Society

Scheme 1. Retrosynthetic Analysis of Lanciaquinone 2 Revealing a Double Claisen Rearrangement, R ) the Phenol Protecting Group
compound is reported to have an optical rotation, [R]D ) 29
(c 0.5, CHCl3); the 1H NMR spectrum contains a four-proton
triplet with two coupling constants (J ) 15.3, 7.6 Hz) for
the two benzylic CH2 groups; and the 13C NMR spectrum
shows a very high field signal (δ ) 8.90) for the quinone
methyl group. Since these data do not appear to be consistent
with structure 2 and we have been unable to contact the
original authors, we decided to resolve the issue by a
synthesis of the reported structure of lanciaquinone.
Our retrosynthesis was based on the Claisen rearrange-
ment-phenol oxidation strategy successfully used in our
synthesis of other quinone natural products.7,10-12 Thus,
lanciaquinone 2 should be readily available by hydrogenation
and oxidation of bisphenol 3, obtained in a double Claisen
rearrangement of the bisallyl ether 4, itself obtained from
the symmetrical diol 5 and the two phenols 6 and 7 (Scheme
1).13-19
protected target molecule, only to fail in the removal of the
MOM groups due to degradation of the final product under
the acidic conditions. We therefore elected to use an
alternative ether, the 2-(trimethylsilylethoxy)methoxy (SEM)
protecting group. The required building blocks were readily
assembled as shown in Scheme 2. The known diol 520 was
Scheme 2. Synthesis of Building Blocks 5, 6, and 7
Preliminary experiments had shown that the choice of
phenol protecting group (R) was crucial, particularly in the
1,2,4-trihydroxybenzene derivative 6 where ester (acetate or
benzoate) or silicon-based protecting groups tended to
migrate from one oxygen to another. Ether-based protecting
groups appeared the most satisfactory, and indeed we
succeeded in preparing the trismethoxymethyl (MOM)
(6) Manguro, L. O. A.; Midiwo, J. O.; Kraus, W.; Ugi, I. Phytochemistry
2003, 64, 855–862.
(7) McErlean, C. S. P.; Moody, C. J. J. Org. Chem. 2007, 72, 10298–
10301.
(8) McErlean, C. S. P.; Sperry, J.; Blake, A. J.; Moody, C. J. Tetrahedron
2007, 63, 10963–10970.
(9) Colucci, M. A.; Couch, G. D.; Moody, C. J. Org. Biomol. Chem.
2008, 6, 637–656.
(10) Davis, C. J.; Moody, C. J. Synlett 2002, 1874–1876
.
(11) Davis, C. J.; Hurst, T. E.; Jacob, A. M.; Moody, C. J. J. Org. Chem.
2005, 70, 4414–4422
.
(12) Jacob, A. M.; Moody, C. J. Tetrahedron Lett. 2005, 46, 8823–
8825
.
(13) For other uses of double Claisen rearrangements in different
contexts, see the following and refs 14-19: Hiratani, K.; Takahashi, T.;
Kasuga, K.; Sugihara, H.; Fujiwara, K.; Ohashi, K. Tetrahedron Lett. 1995,
36, 5567–5570
(14) Tisdale, E. J.; Vong, B. G.; Li, H. M.; Kim, S. H.; Chowdhury, C.;
Theodorakis, E. A. Tetrahedron 2003, 59, 6873–6887
(15) Kotha, S.; Mandal, K. Tetrahedron Lett. 2004, 45, 2585–2588
(16) Kotha, S.; Mandal, K.; Deb, A. C.; Banerjee, S. Tetrahedron Lett.
2004, 45, 9603–9605
.
.
.
.
readily obtained by oxidation of decane-1,10-diol followed
by addition of vinylmagnesium bromide. Phenol 6 (R )
SEM) was conveniently obtained from catechol monobenzyl
ether 8 by oxidation to the quinone 9, reduction to the
(17) Chattopadhyay, S. K.; Biswas, T.; Maity, S. Synlett 2006, 2211–
2214
.
(18) Kotha, S.; Dipak, M. K. Chem.-Eur. J. 2006, 12, 4446–4450
(19) Nicolaou, K. C.; Lister, T.; Denton, R. M.; Gelin, C. F. Angew.
.
Chem., Int. Ed. 2007, 46, 7501–7505
.
4506
Org. Lett., Vol. 10, No. 20, 2008

Scheme 3. Synthesis of the Reported Structure of Lanciaquinone 2
hydroquinone 10, protection with two SEM groups, and
finally hydrogenolysis of the benzyl ether 11. Phenol 7 (R
) SEM) was obtained in two steps from 2,4-dihydroxyben-
zaldehyde by alkylation of the nonhydrogen-bonded phenol
followed by reduction of the formyl group (Scheme 2).
With the three key building blocks in hand, the first
coupling was carried out between the diol 5 and phenol 6
(0.62 equiv) under Mitsunobu conditions, although it was
necessary to use a more reactive phosphine and azodicar-
bonyl dipiperidine (ADDP) as the azo compound to obtain
good yields of the desired allyl ether 13. Coupling of the
remaining allyl alcohol 13 with phenol 7 proceeded under
the same Mitsunobu conditions to give the Claisen precursor
14 (Scheme 3). Heating the bisallyl ether 14 to 200 °C in
m-xylene in a microwave reactor for 2 h resulted in the
desired double Claisen rearrangement to give the bisphenol
15 in acceptable yield. Thereafter, hydrogenation of the two
double bonds and oxidation of the phenols to the quinones
Figure 2.
Selected NMR spectroscopic data (1H in red, 13C in blue).
Org. Lett., Vol. 10, No. 20, 2008
4507

with oxygen in the presence of salcomine21,22 gave the tris-
SEM-protected target molecule 16 in good yield. Finally,
deprotection of the SEM group with fluorosilicic acid gave
the bisbenzoquinone 2, readily converted into the triacetate
17 (Scheme 3).
our synthetic material 2, providing further evidence for the
correctness of compounds 2 and 17 obtained by synthesis.
Hence, we conclude that the natural product lanciaquinone
does not have structure 2, and unfortunately, the inconsisten-
cies (and possible typographical errors such as the optical
rotation) in the data reported for the natural product6 do not
allow us to propose a credible alternative structure.
The structure of the synthetic material 2, and its triacetate
1
17, were confirmed by detailed spectroscopic analysis. H
NMR data confirmed the presence of three hydroxy groups
[δH ) 7.68 (2H) and δH ) 6.85 (1H) all exchangeable with
D2O], two CH [δH ) 6.57 (6′-H) and δH ) 6.01 (6-H)], two
benzylic methylenes (δH ) 2.44), a methyl group (δH ) 2.09)
(5′-Me) coupled to the 6′-H (J ) 1.6 Hz), and a 24H
methylene envelope (δH ) 1.51-1.24) in compound 2.
Analysis of the triacetate 17 confirmed the presence of three
acetate groups and hence three hydroxy groups. Finally,
HMQC and HMBC experiments, summarized in the Sup-
porting Information, show the expected correlations.
Acknowledgment. We thank the EPSRC for support of
this work.
Supporting Information Available: Full experimental
details and characterization data, copies of 1H and 13C NMR
spectra, and detailed comparisons between NMR spectro-
scopic properties of synthetic materials and those reported
for the natural product. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL801697G
The above data are consistent with structures 2 and 17.
However, there are significant differences between these
NMR data and those reported for the natural product and its
triacetate.6 The comparative data are tabulated in the
Supporting Information, and there are major differences in
the 13C NMR data, particularly in the quinone ring that bears
the methyl group, as shown in Figure 2. Figure 2 also shows
a comparison with two known quinone natural products 1823
and 19,24 the NMR data for which closely match those of
(20) Trost, B. M.; Kulawiec, R. J. J. Am. Chem. Soc. 1993, 115, 2027–
2036.
(21) DeJong, C. R. H. I.; Hageman, H. J.; Hoentjen, G.; Mus, W. J.
Org. Synth. 1988, 6, 412–413.
(22) Parker, K. A.; Taveras, D. In Encyclopedia of Reagents for Organic
Synthesis; John Wiley & Sons Ltd: Chichester, 1995; Vol. 6, pp 4423-
4425.
(23) Sontag, B.; Dasenbrock, J.; Arnold, N.; Steglich, W. Eur. J. Org.
Chem. 1999, 1051–1055.
(24) Rukachaisirikul, V.; Kamkaew, M.; Sukavisit, D.; Phongpaichit,
S.; Sawangchote, P.; Taylor, W. C. J. Nat. Prod. 2003, 66, 1531–1535.
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