Complex targets

It is not surprising that multistep synthesis of challenging and complex target molecules is an engine for the discovery of new synthetic principles and novel methodology which may have very broad application. Just as each component of structural complexity can signal a strategy for synthesis, each obstacle to the realization of a chemical synthesis presents an opportunity for scientific discovery. 

Ideally, to ensure the complete removal of the metal ions from the aqueous phase, the complexant and the metal complex should remain in the hydrophobic phase. Thus, the challenges for separations include the identification of extractants that quantitatively partition into the IL phase and can still readily complex target metal ions, and also the identification of conditions under which specific metal ion species can be selectively extracted from aqueous streams containing inorganic complexing ions. 

Minimize overall number of steps and stages preferably using nested MCRs as far as possible as the main strategy in a synthetic plan to a complex target. Overall convergence is maximized dramatically if a plan contains a late-stage MCR that involves components that are themselves terminal products of independent parallel linear sequences. 

An example diversity-oriented synthesis strategy as shown in Scheme 4.14 illustrates how complex targets can be quickly synthesized from smaller molecules via combinations of... 

The nature of the target to be attacked by any drug obviously depends on the specific application. Many cytotoxic metal complexes target DNA because of its importance in replication and cell viability. Coordination compounds offer many binding modes to polynucleotides, including outer-sphere noncovalent binding, metal coordination to nucleobase and phosphate backbone... 

Ziady AG, Kelley TJ, Milliken E, Ferkol T, Davis PB (2002) Functional evidence of CFTR gene transfer in nasal epithelium of cystic fibrosis mice in vivo following luminal application of DNA complexes targeted to the serpin-enzyme complex receptor. Mol Ther 5 413-419... 

The well balanced electronic and coordinative unsaturation of their Ru(II) center accounts for the high performance and the excellent tolerance of these complexes toward an array of polar functional groups. This discovery has triggered extensive follow up work and carbenes 1 now belong to the most popular metathesis catalysts which set the standards in this field [3]. Many elegant applications to the synthesis of complex target molecules and structurally diverse natural products highlight their truely remarkable scope. 

This excellent compatibility of ruthenium catalysts encourages the use of RCM as a key strategic element for the synthesis of complex target molecules as will become evident from the examples discussed in Sect. 5. 

The polycyclic structure of manzamine A 74, an alkaloid with promising antitumor activity, constitutes an ideal testing ground for probing the effciency of RCM. Although no total synthesis of 74 has yet been reported, various approaches to this complex target rely on RCM-based strategies. 

The principles and strategies of retrosynthetic analysis facilitate the discovery of possible synthetic pathways to a complex target structure. Exhaustive and systematic analysis over a period of time generally reveals a surprisingly large number and diversity of such candidate routes. Such... 

The hydroformylation reaction ( oxo reaction ) of alkenes with hydrogen and carbon monoxide is established as an important industrial tool for the production of aldehydes ( oxo aldehydes ) and products derived there from [1-6]. This method also leads to synthetically useful aldehydes and more recently is widely applied in the synthesis of more complex target molecules [7-15,17], including stereoselective and asymmetric syntheses [18-22]. 

Stebbins, C. E., Russo, A. A., Schneider, C., Rosen, N., Hard, F. U., and Pavledch, N. P. (1997). Crystal structure of an Hsp90-geldanamycin complex targeting of a protein chaperone by an antitumor agent. Cell 89, 239—250. 

Bozhenok, L., Wade, P.A., and Varga-Weisz, P. (2002) WSTF-ISWI chromatin remodeling complex targets heterochromatic replication foci. EMBO J. 21, 2231-2241. 

Formation of C-C bonds remains the ultimate challenge to the synthetic chemist. The employment of new synthetic methods in complex target synthesis can be frustrated by a lack of functional group tolerance and substrate specificity. These problems can be somewhat alleviated within conjugate addition reactions by the use of secondary amine catalysts where a number of important and highly selective methods have been developed. Two principle classes of nucleophile have been shown to be effective in the iminium ion activated conjugate addition of carbon nucleophiles to a,P-unsaturated carbonyl systems aryl, heteroaromatic and vinyl... 

A multicomponent reaction (MCR) represents a sequence of bimolecular events leading to products that incorporate essentially all atoms of three or more starting materials. MCRs allow for the rapid and facile access to complex target structures... 

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