Platinum complex compounds trans

Use for resolution of cycloalkenes. W s-Cycloalkenes of intermediate size (Cg-Cjo) should be capable of existing in enantiomeric forms because of the inability of the trans double bond to rotate with respect to the remainder of the molecule. But in the absence of salt-forming groups, resolution cannot be accomplished by the usual methods of forming derivatives. However, Cope et al.s found that the strong tendency of an alkene to complex with a platinum compound provides an effective method of resolution. The complex of ethylene with platinous chloride and (+) or (-)-a-methylbenzylamine exists in only one form since ethylene is symmetrical. But addition of the base to a solution of the platinum complex of trans-cyclooctene opens the way for formation of the diastereoisomeric complexes derived from the R- and S-forms of the base. Fractional crystallization at —20° (liquid at 25°) effected separation. Liberation of the (—)-hydrocarbon from the complex with potassium cyanide gave a product of aD — 411°. 

The most important of the tertiary phosphine complexes of platinum(IV) are Pt(QR3)2X4, generally prepared by halogen oxidation [174] of cis- or trans-Pt(QR3)2X2 (Q = P, As, R = alkyl Q = Sb, R = Me), since direct reaction of the platinum(IV) halides with the ligands leads to reduction. Once made, the platinum(IV) compounds are stable to reduction ... 

The use of this phosphine facilitates assignment of configuration as virtual coupling is observed when the phosphines are trans (section 2.9.5).) Syntheses follow established routes using methyllithium as an alkylating agent the platinum(iV) complexes can be made by direct alkylation of platinum(IV) compounds or by oxidative addition to platinum(II) species. 

DNA polymerases, 5, 1007 Trans effect, 1,16, 26, 315 metal complexes, 2, 705, palladium(II) amine complexes, 5, 1115 platinum complexes, 5, 353, 493 six-coordinate compounds. 1, 49 T ransestcrification metal alkoxide synthesis, 2, 340 Transferases zinc, S, 1002... 

Chiral bis-(binaphthophosphole) (bis(BNP)) ligands have been used in the asymmetric hydroformylation of styrene. In solution, the free diphospholes display fluxional behavior. Consistent with their structure, the reaction of the bis(BNP) compounds with platinum(II) derivatives gives either cis chelate mononuclear complexes or trans phosphorus-bridged polynuclear derivatives. Coordination to platinum enhances the conformational stability of bis(BNP)s and diastereomeric complexes can be detected in solution. In the presence of SnCl2, the platinum complexes give rise to catalysts that exhibit remarkable activity in the hydroformylation of styrene. Under optimum conditions, reaction takes place with high branched selectivity (80-85%) and moderate enantio-selectivity (up to 45% ee). 

Introduction of the allene structure into cycloalkanes such as in 1,2-cyclononadiene (727) provides another approach to chiral cycloalkenes of sufficient enantiomeric stability. Although 127 has to be classified as an axial chiral compound like other C2-allenes it is included in this survey because of its obvious relation to ( )-cyclooctene as also can be seen from chemical correlations vide infra). Racemic 127 was resolved either through diastereomeric platinum complexes 143) or by ring enlargement via the dibromocarbene adduct 128 of optically active (J3)-cyclooctene (see 4.2) with methyllithium 143) — a method already used for the preparation of racemic 127. The first method afforded a product of 44 % enantiomeric purity whereas 127 obtained from ( )-cyclooctene had a rotation [a]D of 170-175°. The chirality of 127 was established by correlation with (+)(S)-( )-cyclooctene which in a stereoselective reaction with dibromocarbene afforded (—)-dibromo-trans-bicyclo[6.1 0]nonane 128) 144). Its absolute stereochemistry was determined by the Thyvoet-method as (1R, 87 ) and served as a key intermediate for the correlation with 727 ring expansion induced... 

The active Pt(IV) compounds are octahedrally coordinated and possess axial bound chloride or—to improve the solubility—hydroxo ligands, i.e., two Y ligands in the trans orientation. These compounds are far more inert than the corresponding Pt(II) compounds that lack these axial ligands. Most likely the Pt(IV) compexes are reduced in vivo to the corresponding Pt(II) complexes, which are in fact the active species (17-19). They can therefore be considered as a type of prodrug that requires in vivo activation (substitution and reduction) to the square-planar Pt(II) compounds to exhibit antineoplastic activity. This hypothesis is supported by the observation that platinum(IV) compounds are unable to react with DNA under ambient conditions (19), and that appreciable amounts of Pt(II) derivatives can be detected in the urine of Pt(IV)-treated patients(fS). 

Platinum(IV) isocyanide complexes PtCU(CNR)2 and [PtCl2(CNR)2(PMe2Ph)2]2+ have been prepared by the addition of Cl2 to the corresponding platinum(II) compounds (equation 118).363 It is probable that the trans influence of the isocyanide ligand on platinum(IV) is greater than that of a tertiary phosphine. 

The cis/trans isomerization of platinum(II) complexes is a subject which will be discussed in some detail when the halide (Group VII) complexes are covered. Nevertheless the importance of reductive elimination reactions of platinum(II) alkyl and aryl complexes makes it imperative that this reaction be discussed here for alkyl and aryl platinum(II) compounds. 

Another report reveals, however, that in vitro DNA-binding assays are insufficient to predict platinum antitumor activity [15]. Primer extension (Fig. 1) was used to identify specific adducts formed by platinum complexes on DNA in HeLa cells. The DNA adduct profile correlated well with in vivo antitumor activity for cis- and trans-DDP, Pt(en)Cl2, and two acridine-tethered platinum complexes. When the complexes were allowed to react with purified DNA in solution, there were no substantial differences in adduct profiles between active and inactive compounds. This result demonstrates that cell-based assays can be better predictors of in vivo activity than in vitro assays, particularly when the in vitro screen does not require aunique, mechanism-based molecular interaction. 

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