Full Paper
[6] As we used different cell lines than the original publication, a direct
comparison with the literature data is not possible.
[8] For a study on the aglycone, see: K. M. Reddy, V. Yamini, K. K. Singarapu,
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[11] For illustrations of this notion by previous projects pursued by our
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tivity of the target became the central theme, although one
might tend to think that such duties are obsolete in the
modern age of ever more sophisticated chromatography and
molecular spectroscopy.[9–11] All issues surrounding mandelali-
de A were ultimately sorted out. An independent investigation
by Xu, Ye, and co-workers reached the same conclusions in
structural and functional terms.[7]
From a purely chemical standpoint, the present study attests
to the power of catalysis for total synthesis. A notable advance
concerns the ability to engage substrates comprising a terminal
alkyne into macrocyclizations by RCAM, which was inconceiva-
ble until very recently. Along the same lines, this study show-
cases a particularly challenging transannular MBH reaction of
a disubstituted enoate, which has hardly any precedent. The
further functionalization of the resulting product revealed
a similarly striking reactivity mode in that it was found that
electron deficient olefins can be selectively dihydroxylated
with OsO4/TMEDA in the presence of significantly more elec-
tron-rich alkenes even if the latter are unencumbered and
readily accessible for the incoming oxidant. Although this ob-
servation is preliminary at this point, it is potentially enabling,
and might therefore become an important spin-off of this total
synthesis enterprise that merits closer inspection.
[13] A. Fürstner, Science 2013, 341, 1229713.
[14] For Z,Z-dienes by RCAM/semireduction, see: a) J. Willwacher, N. Kausch-
Busies, A. Fürstner, Angew. Chem. Int. Ed. 2012, 51, 12041–12046;
Kausch-Busies, E. E. Rubitski, Z. Sobol, M. Schuler, M.-H. Lam, S. Musto, F.
Experimental Section
[15] For E,Z-dienes forged at the Z-configured double bond by RCAM/semi-
DeSouza, L. Turet, M. D. B. Fenster, L. Parra-Rapado, C. Wirtz, R. Mynott,
C. W. Lehmann, Chem. Eur. J. 2007, 13, 115–134.
[16] For Z,E-dienes forged at the E-configured double bond by RCAM/semi-
reduction, see: a) K. Micoine, A. Fürstner, J. Am. Chem. Soc. 2010, 132,
14064–14066; b) K. Micoine, P. Persich, J. Llaveria, M.-H. Lam, A. Mader-
na, F. Loganzo, A. Fürstner, Chem. Eur. J. 2013, 19, 7370–7383.
[17] For a E,E-diene by RCAM/semireduction, see: C. M. Neuhaus, M. Liniger,
All experimental details can be found in the Supporting Informa-
tion. The material includes compound characterization and copies
of spectra of new compounds. The computational part of the Sup-
porting Information provides detailed information on the chosen
computational methods, the DP4 probability analysis, and the con-
formational analysis for 74.
Acknowledgements
Generous financial support by the MPG and the Fonds der
Chemischen Industrie (KekulØ stipend to J.W.) is gratefully ac-
knowledged. We thank K. Holthusen for assistance in the prep-
aration of the glycosyl donor, Dr. A. Maderna (Pfizer Inc) for the
cytotoxicity data, Dr. J. Herrmann and Prof. R. Müller, Helm-
holtz-Institute for Pharmaceutical Reseach Saarland, for the an-
tifungal screen, and the Analytical Departments of our Institute
for invaluable support.
[18] For an RCAM-approach to yet other dienes, see: a) A. Fürstner, O. Lario-
nov, S. Flügge, Angew. Chem. Int. Ed. 2007, 46, 5545–5548; Angew.
[19] For skipped dienes, see: a) V. Hickmann, A. Kondoh, B. Gabor, M. Alcara-
zo, A. Fürstner, J. Am. Chem. Soc. 2011, 133, 13471–13480; b) W. Chała-
daj, M. Corbet, A. Fürstner, Angew. Chem. Int. Ed. 2012, 51, 6929–6933;
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totschnig, A. Fürstner, Chem. Eur. J. 2015, 21, 4529–4533.
[20] For representative cases, see: a) L. G. McCullough, M. L. Listemann, R. R.
6730; b) A. Bray, A. Mortreux, F. Petit, M. Petit, T. Szymanska-Buzar, J.
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Keywords: alkyne metathesis · macrolides · natural products ·
structure elucidation · total synthesis
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[2] P. L. Winder, Ph. D. Thesis, Florida Atlantic University, 2009.
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[5] The reassignment of mandelalide A as the result of the work described
herein was presented at the Symposium for Cooperative Effects, Mün-
ster, Germany on May 9, 2014; the same conclusion was independently
reached in ref. 7 which was published online on May 20, 2014.
Chem. Eur. J. 2015, 21, 10416 – 10430
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