Palladium antitumor activity

Miscellaneous. Reductioa of a palladium salt by CO is the basis of a visual test for ambieat carboa moaoxide (227). Palladium compouads are used as photographic seasitizers (228). The low dimensional mixed valeace compouad Csq g3[Pd(S2C2(CN)2)] 0.5H2O behaves as a semimetal at room temperature (229). Palladium compouads isostmctural with poteat platiaum antitumor compounds have poor antitumor activity (230). 

Ruiz J, Cutillas N, Vicente C, Villa MD, Lopez G, Lorenzo J, Aviles FX, Moreno V, Bautista D (2005) New palladium(II) and platinum(II) complexes with the model nucleobase 1-methylcytosine antitumor activity and interactions with DNA. Inorg Chem 44 ... 

Ruiz J, Villa MD, Cutillas N, Lopez G, de Haro C, Bautista D, Moreno V, Valencia L (2008) Palladium(II) and Platinum(II) Organometallic Complexes with 4, 7-dihydro-5-methyl-7-oxo[l, 2, 4]triazolo[l, 5-a]pyrimidine. Antitumor activity of the platinum compounds. Inorg Chem 47 4490 1505... 

In vitro methods are not widely used to predict the antitumor activity of platinum compounds. Until it is determined what factors render a specific platinum-DNA adduct cytotoxic, the in vitro screens for platinum drugs will be limited. Because a good platinum drug must form DNA adducts, preliminary screening methods have been employed which measure DNA binding alone as a measure of potential antitumor activity. In one such study [13], the DNA binding of palladium and platinum complexes having inter-... 

Some cis complexes of platinum and palladium that show significant antitumor activity. It is thought that the cis complexes work by losing two adjacent ligands and then forming coordinate covalent bonds to adjacent bases on a DNA molecule. 

This methodology also enables stereospecific synthesis of the side-chain of taxol [56]. The A-benzoyl-3-phenylisoserine side chain at C-13 of the taxol molecule is essential for its antitumor activity. The stereoselectivity in this reaction depends on the geometry of the silyl ketene acetal (Eq. 77). The reaction of the (E)-ketene acetal with (i )-27 produces the anti adduct with high stereoselectivity anttsyn = 98 2, 92 % de anti). In contrast, the reaction of the (Z)-silyl ketene acetal with S)-27 produces the enantiomerically pure syn adduct (symanti = > 99 1, > 99 % de syn). Aus, our methodology provides the first practical and efficient route for the preparation of both diastereomers of an a-hydroxy /3-amino ester. The syn adduct 52 is transformed to the desired A-benzoyl-(27 ,35)-phenylisoserine methyl ester by hydrogenolysis over a palladium catalyst then the Schotten-Baumann reaction. 

Other transition metal complexes with cis dichloro ligands have been tested for antitumor activity. The palladium analog cis-[PdCl2(NH3)2] is inactive, prohahly due to the high kinetic lability of Pd(II) compared to Pt(II), and isomerization is facile this process is blocked in the chelated en complex, which is active (16). More inert metal ions such as Rh(III) and Ru(III) also have active analogs (Table VI), and it is likely that some ruthenium complexes will soon enter clinical trials (31-33). 

Along with the total synthesis of (—)-acetomycin, a highly functionalized y-lactone with antitumor activity, Kinderman and Feringa (98TA1215) described the stereoselective hydrogenation of the enantiomerically pure (-h)-(S)-5-acetoxy-2(5// )-furanone 123 in methanol at and in the presence of palladium on carbon ... 

Boufatah N, Gellis A, Maldonado J, Vanelle P (2004) Efficient microwave-assisted synthesis of new sulfonylbenzimidazoIe-4,7-diones heterocyclic quinones with potential antitumor activity. Tetrahedron 60(41) 9131-9137. doi 10.1016/j.tet.2004.07.070 Brain CT, Brunton SA (2002) An intramolecular palladium-catalysed aryl amination reaction to produce benzimidazoles. Tetrahedron Lett 43(10) 1893-1895. doi 10.1016/80040-4039(02) 00132-6... 

The biological activity displayed by the perhydroazulenes, ranging from diuretic and anti-inflammatory to antitumor, combined with the unique bicyclo [6-3-0] system make them very attractive synthetic targets. The approach of Trost and Higushi to this class of compounds, exemplified by the total synthesis of isoclavu-kerin 65 (Scheme 12.12) [34], has the distinctive feature that it allows the simultaneous formation of both the five- and seven-membered rings through a palladium-catalyzed formal [3+2] cyclization as its key step [35]. 

Similarly, the synthesis of ( + )-phyllanthocin (5). the aglycone of the antitumor agent phyllan-thoside, is achieved via a palladium(0)-catalyzed reductive cyclization of an appropriate optically active precursor in a diastereocontrolled asymmetric synthesis24-2 5. An analogous synthesis via a thermal Alder ene cyclization was unsuccessful24. 

This chemistry has provided one of the most direct routes to the indolo[2,3-a]carbazole alkaloid ring system (Scheme 11), a common functionality of several biologically active molecules such as the potent antitumor agent rebeccamycin and arcyriaflavin A. The indolo[2,3-fl]carbazole derivative has been obtained in satisfactory yield through the reaction of l,4-di((9-trifluoroacetamidophenyl)-l,3-butadiyne with 3,4-dibromomaleimide in the presence of tetrakis(triphenylphosphine)palladium(0) and potassium carbonate. The proposed mechanism of this polyannulation process, which generates four new bonds in a single step, is outlined in Scheme 12. 

Oxindoles have been considered as useful heterocycles as they display a wide range of biological properties including antiarthritis [26], antitumor [27], and antiviral [28] activities. Recently, Felpin et al. have developed a methodology based on a tandem Heck/reduction/cyclization (HRC) sequence to synthesize a variety of oxindoles from 2-(2-nitrophenyl)acrylates and aryl diazonium salts catalyzed by palladium [29]. The strategy, outlined in Scheme 12,... 

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