5
cysteine, followed by a high-yielding Wittig olefination step.
Additionally, three quantitative non-chromatographic steps
were involved, with an overall yield of the entire route >75 %.
The versatility of the proposed approach also provides new
hints for the exploration of pretubulysin derivatives.
Accordingly, we herein synthesized three novel fragments
bearing different heterocyclic moieties thus supporting the
broad analoging potential of our proposed approach.
Vandenberghe, E.; Williams, D. C.; Zisterer, D. M.; Lawler, M. Cancer
Res. 2009, 69, 8366-8375.
18. Mulligan, J. M.; Greene, L. M.; Cloonan, S.; Mc Gee, M. M.; Onnis, V.;
Campiani, G.; Fattorusso, C.; Lawler, M.; Williams, D. C.; Zisterer, D. M.
Mol. Pharmacol. 2006, 70, 60-70.
19. Butini, S.; Gemma, S.; Brindisi, M.; Borrelli, G.; Lossani, A.; Ponte, A.
M.; Torti, A.; Maga, G.; Marinelli, L.; La Pietra, V.; Fiorini, I.; Lamponi, S.;
Campiani, G.; Zisterer, D. M.; Nathwani, S. M.; Sartini, S.; La Motta, C.; Da
Settimo, F.; Novellino, E.; Focher, F. J. Med. Chem. 2011, 54, 1401-1420.
20. Brindisi, M.; Gemma, S.; Alfano, G.; Kshirsagar, G.; Novellino, E.;
Campiani, G.; Butini, S. Tetrahedron Lett. 2013, 54, 5387-5390.
21. Ferlini, C.; Cicchillitti, L.; Raspaglio, G.; Bartollino, S.; Cimitan, S.;
Bertucci, C.; Mozzetti, S.; Gallo, D.; Persico, M.; Fattorusso, C.; Campiani,
G.; Scambia, G. Cancer Res. 2009, 69, 6906-6914.
Supplementary data
Supplementary data (experimental methods for the
preparation of intermediates, NMR and ESI-MS data)
associated with this article can be found, in the online version,
at http://dx.doi.org/XXXXXXXXX
Acknowledgement
22. Butini, S.; Gabellieri, E.; Huleatt, P. B.; Campiani, G.; Franceschini, S.;
Brindisi, M.; Ros, S.; Coccone, S. S.; Fiorini, I.; Novellino, E.; Giorgi, G.;
Gemma, S. J. Org. Chem. 2008, 73, 8458-8468.
Financial support from Regione Toscana (Bando Salute
2009) is kindly acknowledged.
23. Butini, S.; Gabellieri, E.; Brindisi, M.; Casagni, A.; Guarino, E.; Huleatt,
P. B.; Relitti, N.; La Pietra, V.; Marinelli, L.; Giustiniano, M.; Novellino, E.;
Campiani, G.; Gemma, S. Bioorg. Med. Chem. Lett. 2013, 23, 85-89.
24. Butini, S.; Gabellieri, E.; Brindisi, M.; Giovani, S.; Maramai, S.;
Kshirsagar, G.; Guarino, E.; Brogi, S.; La Pietra, V.; Giustiniano, M.;
Marinelli, L.; Novellino, E.; Campiani, G.; Cappelli, A.; Gemma, S. Eur. J.
Med. Chem. 2013, 70, 233-247.
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30. ((4-(Ethoxycarbonyl)thiazol-2-yl)methyl)triphenylphosphonium chloride
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1
pure salt 13 (quantitative yield) as an off-white powder. H NMR (300 MHz,
CDCl3) δ 1.32 (t, J = 7.1 Hz, 3H), 4.29 (q, J = 7.1 Hz, 2H), 6.39 (d, J = 14.4
Hz, 2H), 7.57-7.69 (m, 6H), 7.70-7.80 (m, 3H), 7.87-7.99 (m, 6H), 8.03 (s,
1H).
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