Liquid phase combinatorial synthesis

D. P. Curran, S. Hadida, Tris(2-(Perfluorohexyl)tin Hybride A New Fluorous Reagent for Use in Traditional Organic Synthesis and Liquid Phase Combinatorial Synthesis , J. Am. Chem. Soc 1996,118,2531. 

Curran, D. P. Hoshino, M. Stille Couplings with Fluorous Tin Reactants— Attractive Features for Preparative Organic Synthesis and Liquid Phase Combinatorial Synthesis, J. Org. Chem. 1996, 61, 6480-6481. 

Bendale, P.M. and Sun, C.-M., Rapid microwave-assisted liquid-phase combinatorial synthesis of 2-(arylamino)benzimidazoles, /. Comb. Chem., 2002, 4, 359-361. 

As part of an efficient, facile and practical liquid-phase combinatorial synthesis of benzimidazoles under microwave irradiation, the reduction of a polymer bound o -nitroaniline with zinc metal in methanol was completed in a very short time (2 min)61 (Scheme 4.33). However, no detailed reaction conditions were given. 

A demonstration of liquid-phase combinatorial synthesis was recently introduced whereby the highly soluble, but highly crystalline, monomethyl polyethylene glycol (PEG) was employed to allow solution synthesis of a peptide library and solid phase-like purification by a change to a solvent where the PEG was insoluble. The demonstration penta-peptide library yielded the expected anti-P-endorphin binding sequence [65]... 

Han H, Wolfe MM, Brenner S, Janda KD, Liquid-phase combinatorial synthesis. Proc. Natl. Acad. Sci. USA, 92 6419-6423, 1995. 

The concept of liquid-phase combinatorial synthesis (LPCS) was introduced by Han et al. [171] in a paper where a peptide and a sulfonamide libraries were prepared using PEG (polyethylene glycol) as support. The support was chosen because of its successful application in peptide, oligosaccharide and... 

Curran DP, Hoshino M, Stille couplings with fluorous tin reactants Attractive features for preparative organic synthesis and liquid-phase combinatorial synthesis, J. Org. Chem., 61 6480-6481, 1996. 

Yandersteen, AM, Han H, Janda KD, Liquid-phase combinatorial synthesis In search of small-molecule enzyme mimics, Mol. Diversity, 2 89-96, 1996. 

Figure 3. Liquid phase combinatorial synthesis (LPCS) and recursive deconvolution.

Soluble PEG supports have been used for different applications such as the synthesis of peptides (241, 245) and peptidomimetics (246) soluble-supported catalysts (247-249), reagents (250-253), scavengers (254), and traceless linkers (255-257) to improve purification protocols (258, 259) and high-loading PEG-derived soluble supports (260), particularly in the synthesis of arrays of small organic molecules (261-275). Several recent reviews (276-281) illustrate their usefulness but also show how additional efforts could make PEG liquid-phase combinatorial synthesis more reliable. 

Each L13 individual was evaluated as a potential soluble support in liquid-phase combinatorial synthesis. A great variation in the solubility profiles was observed for the 20 copolymers, the most relevant of which are reported in Table 11.2. The copolymer Mi,2-M2,3 was selected, being very soluble in apolar solvents such as THE and diethyl ether, insoluble in polar solvents such as water and alcohol, and nonswelling in any solvent. It thus resulted complementary to PEG-based supports and... 

An extension of the combinatorial synthesis in solution is achieved by the use of soluble polymeric supports [80, 81], which combines some of the advantages of chemistry in solution and on solid phase. The so-called liquid-phase combinatorial synthesis is based on the physical properties of poly (ethylene glycol) monomethyl ether. The polymer is soluble in a variety of aqueous and organic solvents, which allows reactions to be conducted in homogeneous phase whereas the propensity to crystallize in appropriate solvents facilitates the isolation and purification of the compound at each step of the combinatorial synthesis. 

DP Curran, S Haida. Tris(2-(perfluorohexyl)ethyl)tin hydride a new fluorous reagent for use in traditional organic synthesis and liquid phase combinatorial synthesis. J Am Chem Soc 118 2531-2532, 1996. 

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