Journal of the American Chemical Society
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Scheme 4. Completion of the Total Synthesis of Thailanstatin A
(1) and its Methyl Ester (2)a
1
2
3
4
5
6
7
8
9
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aReagents and conditions: (a) Pd(dppf)Cl2•CH2Cl2 (0.02 equiv),
K3PO4 (1.0 equiv),
5 (1.1 equiv), 6 or 6a (1.0 equiv), 1,4-
dioxane/MeCN/H2O (3:1:1), 25 °C, 10 min, 52% for 1, 64% for 2; (b)
TMSCHN2 (3.0 equiv), 3:2 PhMe/MeOH, 0 25 °C, 3 h, quant.
Abbreviations: dppf = diphenylphosphinoferrocenyl.
its congeners, while the stereochemical divergency of the method
to produce tetrasubstituted tetrahydropyrans bodes well for its
application to the construction of a variety of designed analogues
within this family of bioactive molecules for biological evaluation.
Such studies may lead to the identification of useful biological tools
and potential drug candidates to be developed as anticancer drugs
or employed as payloads for ADCs or other cancer cell selective
delivery systems for the purposes of targeted and personalized can-
cer therapies.
ASSOCIATED CONTENT
Supporting Information
Experimental procedures and characterization data for all compounds.
This material is available free of charge via the Internet at
AUTHOR INFORMATION
Corresponding Author
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
D.R. is a University of California, San Diego graduate student; all work
was carried out at Rice University. We thank Drs. Lawrence B. Ale-
many and Quinn Kleerekoper (Rice University) for NMR-
spectroscopic assistance, Drs. Christopher L. Pennington (Rice Uni-
versity) and Ian Riddington (University of Texas at Austin) for mass-
spectrometric assistance, and Dr. James D. Korp (University of Hou-
ston) for X-ray crystallographic assistance. We also thank Yi-Chiang
“Eric” Cheng (University of North Texas Health Science Center) for a
sample of natural thailanstatin A for comparison purposes. This work
was supported by The Cancer Prevention & Research Institute of Tex-
as (CPRIT) and The Welch Foundation (grant C-1819).
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