2
Tetrahedron
Benzodioxinone compounds are thermally and photolytically
O
O
O
O
O
O
O
active towards nucleophiles. It is known that 1,3-benzodioxin-4-
one undergoes photolytic reactions with alcohols to form
salicylate derivatives efficiently.5 In addition, 1,3-benzodioxin-4-
one derivatives have been used in synthetic polymer chemistry.
Our group has studied the synthesis of oligoesters and cross-
linked polymers by photolytic reactions of 1,3-benzodioxin-4-
ones with hydroxyl groups.6-8 Also, thermal decomposition
reactions of 1,3-benzodioxin-4-ones have been studied. However,
the yields were very low and the reactions needed a catalyst.9-11
DCC
O
O
OH
+
DMAP
HO
BnO
OBn
BnO
OBn
8
4
7
88%
1. , Na, PhMe, 110 o
C
5
2. H2/Pd
O
OH
OH
O
O
OH
O
OH
In this study, a new and shorter method is offered to obtain
montegnatol and erythrin starting from orsellinic acid using
benzodioxinone chemistry. The reaction steps can be summarized
as follows: synthesis of a dioxinone derivative of orsellinic acid,
esterification and hydrogenolysis. To increase the yield in the
thermal reactions, we used an excess of sodium in order to
enhance the nucleophilicity of the D-erythritol. Thus, 1,3-
benzodioxin-4-one (4) was reacted with benzyl-protected D-
erythritol (5) to give compound (3) as in Barrett’s pathway. The
reaction was monitored by TLC and mainly two products were
observed. To our surprise, however, GC-MS analysis showed
that there was none of the desired compound (3) in the reaction
mixture. The esterification reaction had proceeded well, but a
mixture of two different deprotected esters was obtained. One of
these products (11) formed unexpectedly, possessing a benzyl
group on the phenol (at 5.37 ppm). Thus, excess sodium metal
caused deprotection of some of the benzyl groups on the aliphatic
side chain, but also at the same time, mediated benzylation of the
sterically suitable aromatic hydroxyl group. The NMR yield of
compound 11 was approximately 70%. Finally, hydrogenolysis
removed the benzyl protecting group to give (-)-montagnetol (1)
(Scheme 2). Thus, (-)-montegnatol was prepared from simple
starting materials in two steps.
HO
OH
2
38%
Scheme 3. Synthesis of (-)-erythrin (2)
The H-NMR, 13C-NMR and physical data of the prepared
compounds were found to be in good agreement with those
reported.4
1
In conclusion, we have developed a facile synthetic pathway
to synthesize biologically important (-)-montagnetol and (-)-
erythrin. Only two starting materials are required for the
syntheses of both compounds. Both of the starting materials are
benzodioxinone derivatives of orsellinic acid. Moreover, as
purification is not necessary before the hydrogenolysis reaction,
this method requires fewer synthetic steps to achieve the target
molecules.
Acknowledgments
We thank Istanbul Technical University, Research Funds for
financial support.
Supplementary Material
Supplementary material for this article is available online at
http:\\pubs.acs.org.
References and notes
1. Choudhary, M. I.; Ali, S.; Thadani, V. M.; Karunaratne, V. 2009,
U.S. Patent number: US20090048332-A1.
2. Rao, S. V.; Seshadri, T. R. Proc. Ind. Acad. Sci. Sect. A 1941,
13A, 199.
3. Manaktala, S. K.; Neelakantan, S.; Seshadri, T. R. Tetrahedron
1966, 22, 2373.
4. Basset, J. F.; Leslie, C.; Hamprecht, D.; White, A. J. P.; Barrett,
A. G. M. Tetrahedron Lett. 2010, 51, 2783-2785.
5. Soltani, O.; Brabander, J. K. D. Angew. Chem. Int. Ed. 2005, 44,
1696-1699.
Scheme 2. Synthesis of (-)-montagnetol (1)
6. Tasdelen, M. A.; Kumbaraci, V.; Talinli, N.; Yagci, Y.
Macromolecules 2007, 40, 4406-4408.
In the second part of this study (Scheme 3), being different
from Barrett’s strategy, we aimed to synthesize erythrin starting
from two orsellinic acid derivatives: benzyl protected 7 and the
1,3-benzodioxin-4-one derivative 4 from orsellinic acid. These
two compounds were reacted in the presence of DCC to afford
new compound 8. Next, 1,3-benzodioxin-4-one 8 possessing an
aromatic ester was treated with benzyl-protected D-erythritol (5)
in the presence of sodium metal, which underwent the ketene
trapping reaction. This was followed by hydrogenolysis of the
crude product without any purification to afford (-)-erythrin. This
strategy has less synthetic steps than those routes reported
previously.
7. Kumbaraci, V.; Talinli, N.; Yagci, Y. Macromol. Rapid. Commun.
2007, 28,72-77.
8. Kumbaraci, V.; Talinli, N.; Yagci, Y. Macromolecules 2006, 39,
6031-6035.
9. Navarro, I.; Basset, J.; Hebbe, S.; Major, S. M.; Werner, T.;
Howsham, C.; Bräckow, J.; Barrett, A. G. M. J. Am. Chem. Soc.
2008, 130, 10293-10298.
10. Ondozabal, H. M.; Barrett, A. G. M. Tetrahedron 2010, 66, 6331-
6334.
11. ElMarrouni, A.; Lebeuf, R.; Gebauer, J.; Heras, M.; Arseniyadis,
S.; Cossy, J. Org. Lett. 2012, 14, 314-317.