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1 Per recenti recensioni su tali sostanze, vedi: (a) M.C. Bibby, Drugs of the

Future 2002, 27,475-480; (b) A. Cirla, J. Mann, Nat. Prod. Rep. 2003, 20, 558-564; (c) R. Rossi, F. Bellina, A. Carpita, Sostanze organiche naturali e

loro derivati o analoghi strutturali con proprietà antineoplastiche, Ed. Plus,

2005, pp.27-38; (d) N. H. Nam, Curr. Med. Chem., 2003, 10, 1697-1722. 2 (a) G.R. Pettit, S.B. Singh, M.L. Niven, E. Hamel, J.M. Schmidt; J. Nat. Prod.

1987, 50, 119-131 (b) S.B. Singh, G.R. Pettit, J. Org. Chem.1989, 54, 4105-4114 (c) G. R. Pettit, S.B. Singh, M. L. Niven, J. Am. Chem.Soc., 1988, 110, 8539-8540

3 (a) G. R. Pettit, S.B. Singh, E. Hamel C.M. Lin, D.S. Alberts, D. Garcia-Kendall, Experientia 1989, 45, 209-211; Erratum in Experientia 1989, 45, 680; (b) A. Cirla, J. Mann, Nat. Prod. Rep. 2003, 20, 558-564.

4 (a) G. R. Pettit, S. B. Singh, M. R. Boyd, E. Hamel, R. K. Pettit, J. M. Schmidt, F. Hogan, J. Med Chem. 1995, 38, 1666-1672; (b) G. R. Pettit, G. M. Cragg, D. L. Herald, J. M. Schmidt, P. Lohavanijaya, Can. J. Chem., 1982, 60, 1374-1376; (c) E. Hamel, Med. Res. Rev. 1996, 16, 207-231; (d) G. R. Pettit, M. R. Rhodes, D. L. Herald, D. J. Chaplin, M. Stratford, R. K. Pettit, J. C. Capuis, D. Oliva, Anti-Cancer drug Des. 1989, 3, 249-254; (f) E. Hamel, in

Microtubule Proteins, J. Avila, Ed. Boca Raton, Fl, CRC Press, 1990, pp. 89-191.

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7 (a)Vedi riferimento 4b; (b) G.R. Pettit, S.B. Singh, US Patent 4.966.237, 1991; (c) K. Gaukroger, J. A. Hadfield, L.A. Hepworth, N. J. Lawrence, A.T. McGrown, J. Org. Chem. 2001, 66, 8135-8138.

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Shnyder, M.C. Bibby, Anticancer Res. 2002, 22, 707-711.(b) G.R. Pettit, M.R. Rhodes, D.L. Herald, D.J. Chaplin, M.R.L. Stratford, E. Hamel, R.K. Pettit, J.C. Capuis, D. Oliva, Anti-Cancer Drug Des. 1998, 13, 981-993; (c) G. R. Pettit, M. R. Rhodes, Anti-Cancer Drug Des. 1998, 13, 183-191; (d) S.E. Holwell, P.A. Cooper, M.J. Thompson, G.R. Pettit, L.W. Lippert III, S. W. Martin, M. C. Bibby, Anti-Cancer Res. 2002, 22 (6C), 3933-3940; (e) C. Kanthou, O. Greco, A. Stratford, I. Cook, R. Knight, O. Benzakour, G. Tozer,

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10 A. Dowlati, K. Robertson, M. Cooney, W.P. Petros, M. Stratford, J. Jesberger, N. Rafie, B. Overmoyer, V. Makkar, B. Stambler, A. Taylor, J. Waas, J.S. Lewin, K.R. McCrae, S.C. Remick, Cancer Res. 2002, 62, 3408-3416.

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78 Per alcuni esempi di 2H-piran-2-oni non naturali con proprietà antitumorali, vedere: (a) I. J. S. Fairlamb, L.R. Morrison, J.M. dickinson, F.Y. Lu, J.P. Shmidt, Bioorg. Med. Chem., 2004, 12, 4285-4299; (b) B. Proksa, D. Uhrin, T. Fusha, Pharmazia, 1986, 41, 703-704; (c) M. Ye, G. Qu, G. Hongzhu, D. Guo, J. Ster. Biochem. Mol. Biol., 2004, 91, 87-98; (d) L.R. Morrison, J.M. Dickinson, I.J.S. Fairlamb, Bioorg. Med. Chem. Lett., 2003, 13, 2667-2671; (e) F. Borges, F. Roleira, N. Milhazes, L. Santana, E. Uriartre, Curr. Med.

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79 A. Gehrt, G. Erkel, T. Anke, O. Sterner, Z. Naturforsch. 1998, 53c, 89-92. 80 F. Bellina, A. Carpita, L. Mannocci, R. Rossi, Eur. J. Org. Chem., 2004,

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81 Y. Horiguchi, T. Saitoh, N. Koseki, H. Suzuki, J. Toda, T. Sano,

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82 T. Dubuffet, B. Cimitiere, G. La Vielle, Synth. Comm., 1997, 27(7), 1123-1131

83 Per una serie di recenti metodi di sintesi di aldeidi 25, vedere: a) A. Procopio, R. Delpozzo, A. De Nino, M. Nardi, G. Sindona, A. Tagarelli, Synlett, 2004,

14, 2633-2635; b) R. Olivera, R. SanMartin, I. Tellitu, E. Dominguez, Tetrahedron, 2002, 58(15), 3021-3037; c) K.A. Bhatia, K. J. Eash, N. M. Leonard, M.C. Oswald, R. S. Mohan, Tetr. Lett., 2001, 42(46), 8129-8132; d) S. Sankararaman, J. E. Nesakumar, J. Chem. Soc., Perkin Trans. I: Org.

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84 a) F. Bellina, M. Biagetti, A. Carpita, R. Rossi, Tetrahedron, 2001, 57, 2857-2870; b) F. Bellina, M. Biagetti, A. Carpita, R. Rossi, Tetr. Lett., 2001, 42, 2859-2863; c) F. Bellina, M. Biagetti, A. Carpita, R. Rossi, 3rd Italian-German Symposium on Organic Chemistry, Ravenna, 30 Marzo-1Aprile 2001, Atti P02. d) F. Bellina, M. Biagetti, A. Carpita, S. Viel, L. Mannina, R. Rossi, Eur.

J. Org. Chem., 2002, 1063-1076; e) M. Biagetti, F. Bellina, A. Carpita, P. Stabile, R. Rossi, Tetrahedron, 2002, 58, 5023-5028; f) F. Bellina, M. Biagetti, A. Carpita, R. Rossi, 23rd Int. Symposium on the Chemistry of

Natural Product, Firenze, 28 Luglio-2 Agosto 2002, P23; g) M. Biagetti, F. Bellina, A. Carpita, R. Rossi, Tetr. Lett., 2003, 44(3), 607-610; h) R. Rossi, A. Carpita, F. Bellina, P. Stabile, L. Mannina, Tetrahedron, 2003, 59, 2067-2081; i) ref. 80.

85 a) A. Belonger, P. Brassard, Can. J. Chem., 1975, 53, 201-208; b) A.A.M. Houwen-Claassen, A.J.H. Klunder, B. Zwanenburg, Tetrahedron, 1989,

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86 a) T. Yao, R.C. Larock, Tetr. Lett., 2002, 43, 7401-7404; b) T. Yao, R.C. Larock, J. Org. Chem., 2003, 68, 5936-5942.

87 a) G. A. Krafft, J. A. Katzenellenbogen, J. Am. Chem. Soc., 1981, 103, 5459-5466; b) S. B. Daniels, E. Cooney, M. J. Sofia, P. K. Chakravarty, J. A. Katzenellenbogen, J. Biol. Chem., 1983, 258, 15046-15053; c) R. W. Spencer, T. F. Tam, E. Thomas, V.J. Robinson, A. Krantz, J. Am. Chem. Soc., 1986,

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88 Per alcuni riferimenti su questo soggetto, vedere: a) M. D. Dowle, D. I. Davies, Chem. Soc. Rev., 1979, 171-197; b) G. Cardillo, M. Orena,

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89 a) V. Jäger, H. J. Günther, Tetr. Lett. 1977, 29, 2543-2546; b) D.G. Garratt, M. D. Ryan, P. L. Beaulieu, J. Org. Chem. 1980, 45, 839-845; c) J. A. Macritchie, T. M. Peakman, A. Silcock, C. L. Willis, Tetr. Lett., 1998, 39, 7415-7418.

90 Per informazioni sul cross-coupling di Sonogashira, vedere: R. Rossi, A. Carpita, F. Bellina, Org. Prep. Proc., 1995, 27(2), 127-160 e bibliografia ivi citata.

91 Per alcuni esempi di sintesi di (Z)-2-penten-4-inoati 5 sostituiti, vedere: a)S. Ma, X. Lu, J. Chem. Soc. Chem. Commun., 1990, 1643; b) S. Ma, X. Lu, Tetr.

Lett., 1990, 31, 7653; c) S. Ma, X. Lu, Z. Li, J. Org. Chem., 1992, 15, 709; d) X. Lu, X. Huang, S. Ma, Tetr. Lett. 1992, 33(18), 2535-2538.

92 a) R. Eastmond, D.R.M. Walton, Tetrahedron, 1972, 28, 4591-4599; b)R. Eastmond, T. R. Johnson, D. R. M. Walton, Tetrahedron, 1972, 28, 4601-4616; c) E. Negishi, N. Okukado, S. F. Lovich, F. T. Luo, J. Org. Chem., 1984, 49, 2629-2632; d) A. S. Kende, C. A. Smith, J. Org. Chem., 1988, 53, 2655-2657; e) L.H. Lee, V. Lynch, R. J. Lagow, J. Chem. Soc., Perkin Trans.

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1, 2000, 2805-2809; f) R. Rossi, F. Bellina, A. Catanese, L. Mannina, D. Valensin, Tetrahedron, 2000, 56, 479-487; g) M. Qian, E. Negishi, Org. Proc.

Res. Dev., 2003, 7, 412-417; h) M. S. Karatholuvhu, P. L. Fuchs, J. A. chem.

Soc. 2004, 128, 14314-14315.

93 Per informazioni sul cross-coupling di Cadiot-Chodkiewicz, vedere: a) P. Cadiot, W. Chodkiewicz, In Chemistry of Acetylenes, H. G. Viehe, Ed.; Marcel Dekker: New York, 1969, pp. 597-647; b) W. Chodkiewicz, Ann.

Chim. (Paris) 1975, 2, 819-869; c) G. Eglinton, W. McCrae, Adv. Org. Chem., 1963, 4, 225-328; d) P. Siemens, R.C. Livingston, F. Diederich, Angew.

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94 I. Nishikawa, S. Shikuya, S. Hosokawa, M. Isobe, Synlett, 1994, 485-486. 95 D. Grandjean, P. Pale, J. Churche, Tetrahedron, 1993, 49(24), 5225-5236. 96 F. Bellina, A. Carpita, R. Rossi, Synthesis, 2004, 15, 2419-2440 e bibliografia

ivi citata.

97 a) F. Bellina, A. Carpita, D. Ciucci, M. De Santis, R. Rossi, Tetrahedron, 1993, 49, 4677; b) R. Rossi, F. Bellina, E. Raugei, Synlett, 2000, 1749; c) V. Farina, S. Kapadia, B. Krishnan, C. Wang, L. S. Liebeskind, J. Org. Chem., 1994, 59, 5905; d) R. Rossi, F. Bellina, M. Biagetti,, Synth. Comm., 1999, 29, 3415; e) H.M.R. Hoffmann, K. Gerlach, E. Lattmann, Synthesis, 1996, 164. 98 Per alcune reazioni di bromodesililazione su vinilsilani, vedere: a) R.B. Miller,

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99 V. P. Bui, T. Hudlicky, T.V. Hansen, Y. Stenstrom, Tetr. Lett., 2002, 43(15), 2839-2841.

100 A. Carpita, R. Rossi, C.A. Veracini, Tetrahedron, 1985, 41(10), 1919-1929. 101 K.S. Feldmann, J. Org. Chem., 1997, 62(15), 4983-4990.

102 Per alcuni esempi di questi metodi vedere: a) M. Seto, Y. Aramaki, T. Okawa, N. Miyamoto, K. Aikawa, N. Kanzaki, S. Niwa, Y. Iizawa, M. Baba, M. Shiraishi, Chem. Pharm. Bull., 2004, 52(5), 577-590, b) M. A. Zhuravel S. T. Nguyen, Tetr. Lett., 2001, 42, 7925-7928.

103 H. Fang, G. Kaur, J. Yan, B. Wang, Tetr. Lett., 2005, 46, 1671-1674.

104 Nel nostro laboratorio è stata usata anche con acidi (Z)-3-bromopropenoici: vedere riferimento 84a

105 Vedi riferimento 80 e bibliografia ivi citata.

106 a) F. Bellina et. Al. Tetrahedron, 2000, 56, 479-487; b)V. Ratovelomana, G. Linstrumelle, Tetr. Lett., 1981, 22, 315-318; c) R. Eastmond, D.R.M: Walton,

Tetrahedron, 1992, 28, 4591-4599.

107 Sull’instabilità di tali diini vedere: a) A.S. Kende, C.A. Smith, J. Org. Chem., 1988, 53, 2655-2657; b) R. Eastmond, T.R. Johnson, D.R. M. Walton,

Tetrahedron, 1972, 28, 4601-4616; c) R. Eastmond, D.R.M. Walton,

Tetrahedron, 1972, 28, 4591-4599; d) E. Negishi, N. Okukodo, S.f. larich, F.T. Luo, J. Org. Chem., 1984, 49, 2629-2632.

108 J. Kristensen, M. Lysèn, P. Vedasø, M. Begtrup, Org. Lett., 2001, 3(10), 1435-1437.

109 S. Urgaonkar, J.G. Verkade, J. Org. Chem. 2004, 69, 5752-5755. 110 D.R. Coulson, Inorg. Synth. 1972, 13, 121

111 T. Hayashi, M. Konishi, Y. Kobori, M. Kumada, T. Higuchi, K. Hirotsu, J:

Am. Chem. Soc., 1984, 106, 158.

112 M. X.-W Jiang, M Rawat, W. D Wulff, J. Am. Chem. Soc., 2004, 126(19), 5970-5971.

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113 M. Abarbi, J.L. Parrain, J.C : Cintrat, A. Duchene, Synthesis, 1996, 1, 82-86. 114 Ali H. Al. Ha Kim, A. H. Haines, Tetr. Lett., 1982, 23(50), 5295-5298. 115 D. Grandjean, P. Pale, J. Chuche, Tetrahedron, 1993, 49(24), 5225-5226.

Riferimenti

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