Combinatorial applications

In order to demonstrate the potential of these resin-bound products for combinatorial applications, the readily prepared nitroalkenes were subsequently employed in Diels-Alder reactions with 2,3-dimethylbutadiene [56], In addition, the resin-bound nitroalkenes were also used in a one-pot , three-component tandem [4+2]/[3+2] reaction with ethyl vinyl ether and styrene. 

To better understand the catalytic mechanism of DHFR and to use this information for the design of potent DHFR-specific inhibitors, we evaluated the proton and hydride transfers using an integrated ab initio Quantum Mechanics/Molecular Mechanics (QM/MM) approach in combination with FEP technology. The combinatorial application of these methods enabled us to propose a precise path along which the proton and hydride ion are transferred and to address the key structural and energetic changes associated with catalysis. 

A. de Meijere, H. Niiske, M. Es-Sayed, T. Labahn, M. Schroen, S. Brase, New Efficient Multicomponent Reactions with C-C Coupling for Combinatorial Application in Liquid and on Solid Phase , Angew. Chem. Int Ed. 1999, 38, 3669-3672. 

The functionalisation of commercially available standard solid supports is of common interest for combinatorial applications to enable a broad range of reactions to be studied. Since these transformations usually require long reaction times under conventional thermal conditions, it was obvious to combine microwave chemistry with the art of resin functionalisation. 

Wong et al.27 described a similar method and the first combinatorial application thereof in solution phase in 1998. As part of this methodology, the use of a methyl 6-hydroxyhexanate galactoside building block is presented (Fig. 11). 

The solid-phase synthesis of a-amino acids via alkaloid-catalyzed alkylation has been investigated by the O Donnell group [64, 65]. The solid-phase based synthetic approach is particularly useful for rapid preparation of a-amino acids for combinatorial application. The concept of this solid-phase synthetic approach, which comprises three key steps, is shown in Scheme 3.22 (for formation of (R) enantiomers). First, solid-phase bound glycine, 51, is converted into its benzophenone imine de-... 

Over the years, a number of cleavable linkers that are acid labile, base labile, or photol-abile have been developed for solid-phase peptide synthesis. (This topic has been covered in detail by several review papers [34-36].) For libraries that require the linker to be cleaved before screening, most of these conventional linkers can be used. Several unconventional linkers have been found to be particularly useful and user-friendly for combinatorial applications (see Fig. 1). Among them are methionine-containing linker [37] and safety-catch benzylhydrylamine linker 1 [38], Bray et al. [39] have utilized an orthogonal peptide-resin linker 2 which allows the final deprotection and removal of contaminating chemicals and the peptide is later released into an aqueous buffer. Hoffmann and Frank [40] recently described a novel safety-catch linker 3 based on the intramolecular catalytical... 

While PEG-based supports are widely used for liquid-phase combinatorial chemistry, other non-PEG-based soluble polymers have also been reported for combinatorial applications. A recent review (276) contains an exhaustive list of homo- and copolym-eric soluble supports used in peptide, oligonucleotide, and oligosaccharide synthesis, including combinatorial chemistry. Two of these supports have also been used for small organic molecule synthesis. Homopolymeric polyvinyl alcohol was used in conjunction with PEG for a protection/derivatization strategy in solution (284), and the copolymer between isopropylacrylamide and acrylic acid was used in the catalytic hydrogenation of a Cbz group (285). 

The specificity of many components of DEBS has been thoroughly studied to allow its careful manipulation (268-272), and its potential for combinatorial biosynthesis including several combinatorial applications via rational modifications of DEBS has been thoroughly reviewed (251, 252, 273-279). Other large modular PKS enzymes have also been characterized (280-288) and will eventually be used to design and... 

A system for combinatorial polymerization of conductive polymers based on electrical addressation was reported.43,47 This same approach was used also for preparation of DNA and protein-arrays.10,48 In the case of combinatorial applications,... 

Combinatorial electrosynthesis was accomplished in the electrochemical robotic system. Transferring classical electrosynthesis into the wells of a microtiter plate allows for working with an electrolyte volume of only -250 pi. The significantly decreased volume makes the approach potentially applicable for combinatorial applications. Moreover, the electrochemical robotic system is able to additionally perform a voltammetric in situ analysis for quality control. 

An active carbonate resin 2a has also been prepared from Wang resin and used to anchor a multifunctional benzylamine derivative for a combinatorial application. Final products were cleaved using TFA-CH2CI2 (1 1)... 

Recently we became interested in the combinatorial application of the above method, that is the utilization of the te-enaminone approach in the parallel solution-phase synthesis of the title compounds (09JCC500). 

Ford L.R., Fulkerson D.R. (1959) A network flow feasibility theorem and combinatorial applications. Canad. Journ. Math. 

Combinatorial applications of °Y and ablative techniques such as RFA and cryo-ablation may provide an option for those patients who would otherwise require surgical resection, but are at high surgical risk due to co-morbidities or prefer less invasive means of treating their disease. Y has been shown to reduce tumor burden in downstaging to transplant or resection for HCC patients [55-57], In patients presenting with tumors which are not amenable to ablative therapy due to excessive size (6-8 cm), °Y microspheres could be used to reduce these lesions (< 3 cm), followed by the use of ablative therapy to effect further response. This presumes... 

Brase and Schroen very recently developed a new cleavage-Heck coupling strategy for combinatorial applications (Scheme Starting from Merrifleld resin, an immobi-... 

In a trisp there could be several simplices with the same set of vertices, and furthermore, the boundary of every simplex may have self-identifications. In the combinatorial applications, we shall usually have spaces without such self-identifications. Therefore, it is useful to distinguish this special case by a separate definition. 

Remark 15.20. When X is a CW complex, the open covering in Theorem 15.19 may be replaced by a covering by subcomplexes. This is the formulation that turns out to be most useful for combinatorial applications. More generally, it works for coverings such that (X, X ) is an NDR-pair, for all i /. 

A188] N. Alon, Some recent combinatorial applications of Borsuk-type theorems, Algebraic, extremal and metric combinatorics, 1986 (Montreal, PQ, 1986), pp. 1-12, London Math. Soc. Lecture Note Ser., 131, Cambridge Univ. Press, Cambridge, 1988. 

WZZ99] V. Welker, G.M. Ziegler, R. Zivaljevic, Homotopy colimits - comparison lemmas for combinatorial applications, J. Reine Angew. Math. 509 (1999), pp. 117-149. 

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