Combinatorial libraries dynamic

Another example for the use of hydrogen as reductant is observed in the reduction of imine [5b]. New imine reductase activity has been discovered in the anaerobic bacterium Acetobacterium woodii by screening a dynamic combinatorial library of virtual imine substrates, using a biphasic water-tetradecane solvent system. 

The head-to-tail-coupling reactions described above are potentially useful in the design of dynamic combinatorial libraries. Features of these reactions include the rapid and reversible formation of carbon-carbon bonds, multifunctional ene-imine building blocks, and formation of stereo centers upon ene-imine linkage. Support for template-directed synthesis utilizing ene-imine building blocks is the formation of a poly ene-imine species that could recognize 3 -GGA-5 sequences of DNA.48 It is noteworthy that some polyene-imines are helical and could form a triple helix with DNA. 

Otto S, Severin K (2007) Dynamic Combinatorial Libraries for the Development of Synthetic... 

Wipf et al. <2005OL4483> elaborated a new metathesis method including ring opening in order to generate dynamic combinatorial libraries. The transformation is shown in Scheme 12. The essence of this method is the recognition that an equilibrium takes place with 93 and an aldehyde in aqueous conditions at pH 4 in a phosphate buffer. With the help of this transformation, a series of new R2-substituted products 94 - not available via direct ring closure - have been synthesized. 

Hydrogen-Bonding Templates in Dynamic Combinatorial Libraries 120... 

In the following sections, examples of hydrogen-bonding templates for the synthesis of macrocycles, cages, interlocked species, helicates and for the photochemical reaction of olefins will be discussed. The use of hydrogen-bonding templates in dynamic combinatorial libraries will also be presented. 

Chemical templates are being increasingly employed for the development of dynamic combinatorial libraries (DCL) [94-98]. These (virtual) libraries of compounds are produced from all the possible combinations of a set of basic components that can reversibly react with each other with the consequent potential to generate a large pool of compounds. Because of the dynamic equilibria established in a DCL, the stabilization of any given compound by molecular recognition will amplify its formation. Hence the addition of a template to the library usually leads to the isolation of the compound that forms the thermodynamically more stable host-guest complex (see Scheme 37). 

Scheme 40 Synthesis of receptor 80-S-S-80 from a dynamic combinatorial library based on 80-SH and 81-SH. The receptor is amplified in the presence of a tripeptide template...

L., Granata, C., O Reilly, M., Wyatt, P.G., Jhoti, H. Detection of ligands from a dynamic combinatorial library by X-ray crystallography. Angew. Chem. Int. Ed. Engl. 2003, 42, 4479-4482. 

A reversible Ugation technique was desired that would aUow the use of the mPE system in dynamic combinatorial libraries (DCL) in an effort to identify masterpiece sequences [81]. The imine bond metathesis is known to have an equilibrium constant close to unity, undergoes reactions at reasonable rates at room temperature, and has a geometry that is compatible with the phenylacetylene unit [82] therefore it was chosen as a component for mPEs. 

Other terms have been employed for this general concept, including self-assembled combinatorial libraries, constitutional dynamic chemistry, and virtual combinatorial libraries . Dynamic combinatorial chemistry and dynamic combinatorial library seem to have found the broadest usage, while virtual combinatorial library is perhaps best reserved for conditions under which library members form at concentrations below detection limits in the absence of target (e.g.. Reference 81). 

Ludlow, R. F. Otto, S. Two-vial, LC-MS identification of ephedrine receptors from a solution-phase dynamic combinatorial library of over 9000 components. J. Am. Chem. Soc. 2008,130, 12218-12219. 

Wessjohann, L. A. Rivera, D. G. Leon, F. Freezing imine exchange in dynamic combinatorial libraries with Ugi reactions Versatile access to tern-plated macrocycles. Org. Lett. 2007, 9,4733 736. 

Ziach, K. Jurezak, J. Controlling and measuring the equilibration of dynamic combinatorial libraries of imines. Org. Lett. 2008,10, 5159-5162. 

Bunyapaiboonsri, T Ramstrom, H. Ramstrom, O. Haiech, J. Lehn, J.-M. Generation of bis-cationic heterocyclic inhibitors of Bacillus subtilis HPr kinase/phosphatase from a ditopic dynamic combinatorial library. J. Med. Chem. 2003,46, 5803-5811. 

Wipf, R Mahler, S. G. Okumura, K. Metathesis reactions of pyrazolot-riazinones generate dynamic combinatorial libraries. Org. Lett. 2005, 7, 4483 486. 

Berkovich-Berger Lemcoff, N. G. Eacile acetal dynamic combinatorial library. Chem. Commun. 2008, 1686-1688. 

LeClaire, J. Vial, L. Otto, S. Sanders, J. K. M. Expanding diversity in dynamic combinatorial libraries Simultaneous exchauge of disulfide and thioester linkages. Chem. Commun. 2005,1959-1961. 

Ingerman, L. A. Waters, M. L. Photoswitchable dynamic combinatorial libraries Coupling azobenzene photoisomerization with hydrazone exchange. J. Org. Chem. 2009, 74, 111-117. 

Buryak, A. Severin, K. Easy to optimize Dynamic combinatorial libraries of metal-dye complexes as flexible sensors for tripeptides. J. Comb. Chem. 2006, 8, 540-543. 

Goral, V. Nelen, M. I. Eliseev, A. V. Lehn, J. M. Double-level orthogonal dynamic combinatorial libraries on transition metal template. Proc. Natl. Acad. Sci. U.S.A. 2001,98,1347-1352. 

Grote, Z. Scopelliti, R. Severin, K. Adaptive behavior of dynamic combinatorial libraries generated by assembly of different building blocks. Angew. Chem. Int. Ed. 2003,42, 3821-3825. 

Severin, K. The advantage ofbeing virtual-Target-induced adaptation and selection in dynamic combinatorial libraries. Chem. Eur. J. 2004,10,2565-2580. 

Corbett, P. T Sanders, J. K. M. Otto, S. Systems chemistry Pattern formation in random dynamic combinatorial libraries. Angew. Chem. Int. Ed. 2007, 46, 8858-8861. 

Ramstrom, O. Lehn, J.-M. Drug discovery by dynamic combinatorial libraries. Nat. Rev. Drug Discov. 2002,1, 26-36. 

Bunyapaiboonsri, T. Ramstrom, O. Lohmann, S. Lehn, J.-M. Peng, L. Goeldner, M. Dynamic deconvolution of a pre-equilibrated dynamic combinatorial library of acetylcholinesterase inhibitors. Chembiochem 2001, 2, 438-444. 

Hochgiirtel, M. Biesinger, R. Kroth, H. Piecha, D. Hofmann, M. W. Krause, S. Schaaf, O. Nicolau, C. Eliseev, A. V. Ketones as building blocks for dynamic combinatorial libraries Highly active neuraminidase inhibitors... 

Valade, A. Urban, D. Beau, J.-M. Target-assisted selection of galactosyltrans-ferase binders from dynamic combinatorial libraries. An unexpected solution with restricted amounts of the enzyme. Chembiochem 2006, 7,1023-1027. 

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