163086-45-1Relevant academic research and scientific papers
Antineoplastic Agents. 291. Isolation and Synthesis of Combretastatins A-4, A-5, and A-6
Pettit, George R.,Singh, Sheo Bux,Boyd, Michael R.,Hamel, Ernest,Pettit, Robin K.,et al.
, p. 1666 - 1672 (1995)
The antineoplastic constituents of Combretum caffrum (Eckl. and Zeyh) Kuntze (Combretaceae family), a species indigenous to South Africa, have been investigated.Subsequently we isolated a series of closely related bibenzyls, stilbenes, and phenanthrenes from C. caffrum.Some of the stilbenes proved to be potent antimitotic agents which inhibited both tubulin polymerization and the binding of colchicine to tubulin.Combretastatin A-4 has been shown to be the most potent cancer cell growth inhibitor of the series.Presently this cis-stilbene is the most effective inhibitor of colchicine binding to tubulin and the simplest natural product yet described with such potent antitubulin effects.Combretastatin A-4, A-5, and A-6 were also found to inhibit growth of Neisseria gonorrhoeae.Details of the isolation and syntheses of combretastatins A-4 (2a), A-5 (2c), and A-6 (3a) have been described.
Antineoplastic agents. 578. synthesis of stilstatins 1 and 2 and their water-soluble prodrugs
Pettit, George R.,Thornhill, Andrew,Melody, Noeleen,Knight, John C.
experimental part, p. 380 - 388 (2009/12/04)
Efficient syntheses of 3,4-methylenedioxy-4′,5-dimethoxy-2′, 3′-dihydroxy-Z-stilbene (stilstatin 1, 2), 3,4,4′-trimethoxy- 2′,3′,5-trihydroxy-Z-stilbene (stilstatin 2, 5), and respective phosphate prodrugs have been summarized. Both 2 and 5 were accessed via a convergent step synthesis using phosphonium bromides 6 and 21 in Wittig reactions with 2,3- bis(tert-butyldimethylsilyloxy)-4′-methoxybenzaldehyde 14. Deprotection of silyl ethers 15 and 26 with TBAF furnished 2 and 5, respectively. Phosphorylation of 2 and 5 afforded the phosphoric acid intermediates 17 and 28 for prodrug development. These phosphoric acid precursors were employed in parallel series of reactions to produce a selection of metal cation prodrug candidates. The biological activities of stilstatins 1 (2)and2(5) and their respective prodrugs were evaluated against a panel of one murine (P388) and six human cancer cell lines. Compared to combretastatin A-2 (1), stilstatin 1 (2) has an additional vicinal hydroxy group on the B ring, the presence of which was detrimental to the cancer cell line potency; in vivo, however, compound 2 would be predicted to have greater anticancer activity resulting from the o-quinone mechanism of action analogous to that of combretastatin A-1 (4). The substitution of a hydroxy group for a methoxy group on the A ring of combretastatin A-1 (4), resulting in stilstatin 2 (5), gave rise to a modest level of inhibition consistent with that found for 4 against cancer cell lines.
