Journal of the American Chemical Society
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Diterpenes from Marine Organisms. Chem. Biodiversity 2018, 15,
e1700276.
4. (a) Langschwager, W.; Hoffmann, H. M. R. Ring-Chain
Tautomerism Provides Route to 7a-Hydroxy-3a-methyl-2,7-
1
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form of the antiproliferative antimicrobial metabolite my-
rocin C (1). Key to the success of this approach was the
development of a powerful annulation strategy that forges
the central ring of the target in a single step from two syn-
thetic precursors of similar complexity. With access to 7,
we are now in position to probe its antiproliferative activ-
ity and determine its biological target. The fragment cou-
pling reaction we have developed should be amenable to
the synthesis of other pimarane diterpenes.
a
dioxoperhydrobenzofuran. Synthesis of the Hydroxy γ-Lactone
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Secondary Metabolites from the Marine Endophytic Fungus Apiospora
montagnei. J. Nat. Prod. 2004, 67, 1058. (b) Tsukada, M.; Fukai, M.;
Miki, K.; Shiraishi, T.; Suzuki, T.; Nishio, K.; Sugita, T.; Ishino, M.;
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ASSOCIATED CONTENT
6.
Chu-Moyer, M. Y.; Danishefsky, S. J. A Remarkable
Cyclopropanation: The Total Synthesis of Myrocin C. J. Am. Chem.
Soc. 1992, 114, 8333.
7. Chu-Moyer, M. Y.; Danishefsky, S. J. The Mode of Action of
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1993, 34, 3025.
8. For a review of natural products that damage DNA by nucleotide
addition to an activated cyclopropane, see: Wolkenberg, S. E.; Boger,
D. L. Mechanisms of in Situ Activation for DNA-Targeting Antitumor
Agents. Chem. Rev. 2002, 102, 2477.
9. This disconnection drew inspiration from a related elegant
fragment coupling employed by Baran and co-workers en route to (–)-
maoecrystal V. See: Cernijenko, A.; Risgaard, R.; Baran, P. S. 11-Step
Total Synthesis of (−)-Maoecrystal V. J. Am. Chem. Soc. 2016, 138,
9425.
The Supporting Information is available free of charge on
the ACS Publications website. The Supporting Information
file contains detailed experimental procedures and charac-
terization data for all new compounds.
AUTHOR INFORMATION
Corresponding Author
Funding Sources
No competing financial interests have been declared.
10. Johnson, C. R.; Adams, J. P.; Braun, M. P.; Senanayake, C. B.
W.; Wovkulich, P. M.; Uskokovic, M. R. Direct α-Iodination of
Cycloalkenones. Tetrahedron Lett. 1992, 33, 917.
Financial support from the National Institutes of Health
(Ruth L. Kirschstein National Research Service Award
F31CA213964-03 to C.E.) and Yale University is gratefully
acknowledged.
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