LETTER
Total Synthesis of Monascusic Acid B
865
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The major diastereomer was separated and demonstrated
to be monascusic acid B (1). The physical (specific rota-
tion) and spectroscopic properties (1H and 13C) of 1 were
found to be identical to those reported for natural
monascusic acid B,2 thus confirming the assigned struc-
ture. The overall yield of 1 from 4 was 18% and the enan-
tiomeric excess of the compound 1 was found to be 93%
as measured by chiral HPLC.
In conclusion, we have developed the first concise, stereo-
selective total synthesis of monascusic acid B starting
from commercially available (R)-(+)-pulegone employing
the Horner–Wadsworth–Emmons and Julia–Kocienski
olefination reactions and Lewis acid catalyzed intramo-
lecular Diels–Alder cyclization as the key steps. This syn-
thetic approach can be employed to synthesize other
natural secondary metabolites possessing a similar deca-
lin substructure.
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(9) The phosphonate 9 can be readily prepared by heating
commercially available ethyl 4-bromocrotonate with
triphenylphosphine in the absence of solvent at 110 °C for
14 h.
Acknowledgment
The authors thank CSIR and UGC, New Delhi for financial assi-
stance. They are also grateful to the NMR, Mass, and IR Divisions
of IICT for spectroscopic analyses.
(10) Baudin, J.; Harean, G.; Jullia, S. A.; Ruel, O. Tetrahedron
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(11) The sulfone 11 required for Julia olefination was prepared
by reducing methyl crotonate with DIBAL-H to the
corresponding alcohol which was subjected to Mitsunobu
conditions (triphenyl phosphine, diisopropyl azodi-
carboxylate, 2-mercaptobenzothiazole) to furnish the
desired benzothiazolyl sulfide; followed by ammonium
molybdate catalyzed H2O2 oxidation of the thioether to
produce the sulfone.
(12) Das, B.; Veeranjaneyulu, B.; Balasubramanyam, P.;
Srilatha, M. Tetrahedron: Asymmetry 2010, 21, 2762.
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Acta Chem. Scand. 1973, 27, 888.
Supporting Information for this article is available online at
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References and Notes
(1) Part 74 in the series ‘Synthetic Studies on Natural Products’.
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(d) Kumar, J. N.; Das, B. Tetrahedron Lett. 2013, 54, 3865.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 863–865