Organic Letters
Letter
and accounted for the remaining 23 and 20% yields.20 In this
regard, we tentatively concluded that the series of natural
products belonging to this family might also exist as complex
mixtures of regioisomers, diastereomers, and enantiomers;
however, compelling evidence by a naturally occurring source
was still worth pursuing. The existence of these diverse isomers in
nature is presumably due to either the late-stage biosynthetic
domino process of 4 or a lack of stereo- and regioselectivity in the
nonenzyme-mediated biosynthetic reactions of intermediate 7.
Thus, this biomimetic domino process between 4 and potential
natural intermediate 7 collectively showed the remarkable
promise held by natural metabolites for architectural establish-
ment.
In summary, the evolutionary record of chemical entities
encoded by nature’s molecular archive inspired us to explore a
fascinating potential biosynthetic pathway for myrtucommulone
J and myrtucommuacetalone and concomitantly reexamine their
biosynthetically feasible structures. This led us to achieve their
first biomimetic total syntheses together with structural revision
of 1. Our strategy hinged on a biosynthetic domino hemi-
acetalization/dehydration/[3 + 3] cycloaddition sequence and
held the promise of evaluating the likelihood of the biosynthetic
path of these natural products. Complementing the efficiency
and simplicity of the developed synthetic route, this method-
ology can also provide a route for the rapid assembly of other
such acylphloroglucinol-derived products in a practical fashion
and in sufficient quantities for the needs of drug discovery.
Further investigations will be directed toward this goal and will
be reported in due course.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
(10) (a) Bouzabata, A.; Boussaha, F.; Casanova, J.; Tomi, F. Nat. Prod.
Commun. 2010, 5, 1659. (b) Weyerstahl, P.; Marschall, H.; Rustaiyan, A.
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(11) Details for the synthetic process of α,β-unsaturated ketone 9 with
■
S
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1992, 35, 1209. (b) Leuner, K.; Heiser, J. H.; Derksen, S.; Mladenov, M.
I.; Fehske, C. J.; Schubert, R.; Gollasch, M.; Schneider, G.; Harteneck,
Experimental procedures and spectral data for all new
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(c) Kwak, Y. S.; Bakker, P. A.; Glandorf, D. C.; Rice, J. T.; Paulitz, T. C.;
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(13) When 13g−l and 9 were treated with TFA in toluene/THF, the
desired reaction did not take place.
̈
AUTHOR INFORMATION
Corresponding Authors
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ORCID
(14) The yields for 16c−f were exceptionally lower than 50% under
standard conditions within at least 3 d.
(15) Liu, H. X.; Chen, K.; Tang, G. H.; Yuan, Y. F.; Tan, H. B.; Qiu, S.
X. RSC Adv. 2016, 6, 48231.
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Shinada, T. Asian J. Org. Chem. 2016, 5, 855.
(17) Yu, B. X.; Jiang, T.; Quan, W. G.; Li, J. P.; Pan, X. F.; She, X. G.
Org. Lett. 2009, 11, 629.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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(18) Shibuya, M.; Tomizawa, M.; Suzuki, I.; Iwabuchi, Y. J. Am. Chem.
Soc. 2006, 128, 8412.
We thank the National Natural Science Foundation of China
(No. 81502949, 31600271, 81773602), Natural Science
Foundation of Guangdong Province (2015A030310482,
2016A030313149), and Frontier Science Key Program of
Chinese Academy of Sciences (No. QYZDB-SSW-SMC018)
for financial support.
(19) Zhou, W. L.; Tan, H. B.; Qiu, S. X.; Chen, G. Y.; Liu, H. X.; Zheng,
C. Tetrahedron Lett. 2017, 58, 1817.
(20) All of 1, 2, 27, and 28 were obtained as isomeric forms due to the
tautomeric equilibrium of the enolized syncarpic acid with different
ratios. This equilibrium for 1 was clearly revealed in ref 4.
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