Condensation multiple component

Armstrong, R.W., Combs, A.R, Tempest, P.A., Brown, S.D., Keating, T.A. (1996) Multiple-Component Condensation Strategies for Combinatorial Library Synthesis. Accounts of Chemical Research, 29, 123-131. 

Wong and co-workers [22] also applied the methodology in the preparation of a library of neomycin B mimetics (Fig. 6). Two libraries were prepared by a multiple-component condensation of neamine derived aldehyde, f-butyl isocyanide or isocyanoacetic acid methyl ester, CBZ-N amino acids (xl3) and a glycine conjugated polyethylene glycol methyl ether. The products of the reaction were isolated by precipitation. 

Armstrong RW, Combs AP, Tempest PA, Brown SD, Keating TA, Multiple-component condensation strategies for combinatorial library synthesis, Acc. Chem. Res., 29 123-131, 1996. 

As early as 1961, Ugi [55] theorized the use of multicomponent reactions for the generation of large collections of compounds and, in the following years, other related works were reported [56-58]. It was only recently, though, that the full potential of multiple component condensations (MCCs) for the generation of combinatorial libraries became apparent, due to the efforts of major pharmaceutical industries and academic research groups. 

Mukhopadhyay M, Bhatia B, Iqbal J, Cobalt catalyzed multiple component condensation route to /1-acetamido carbonyl compound libraries, Tetrahedron Lett., 38 1083-1086, 1997. 

Park WKC, Auer M, Jaksche H, Wong CH, Rapid combinatorial synthesis of aminoglycoside antibiotic mimetics use of a polyethylene glycol-linked amine and a neamine-derived aldehyde in multiple component condensation as a strategy for the discovery of new inhibitors of the HIV RNA Rev responsive elements, J. Am. Chem. Soc., 118 10150-10155, 1996. 

Armstrong RW, Brown SD, Keating TA, Tempest PA, Combinatorial synthesis exploiting multiple-component condensations, microchip encoding and resin capture, in Combinatorial Chemistry Synthesis and Application (Eds. Wilson SR, Czarnik AW), pp. 153-190, 1997, John Wiley Sons, New York. 

Both Siegel et al. (122) and Lawrence et al. (123) have described automated systems for the purification of small arrays of amines and amides. A 48-member array of P-amino alcohols prepared from epoxides and amines was purified using SPE by Shuker et al. (124). Blackburn et al. (125) have described the purification of a 60-member 3-aminoimidazo[l,2-fl]pyridine array obtained from a multiple-component condensation, and Bussolari et al. (126) purified a small array of phenylpropyl amines obtained from dihydrocoumarins and amines. A few applications where ion-exchange resins have been substituted with other solid phases have also recently appeared. For example, the purification of several carbohydrate arrays tagged as hydrophobic O-laurates using Ci8 silica producing up to 10-30 mg of >90% pure individuals was described by Nilsson et al. (127), and Curran et al. purified fluorous-... 

Tempest PA (2005) Recent advances in heterocycle generation using the efficient Ugi multiple-component condensation reaction. Curr Opin Dmg Discov Devel 8 776-788... 

The selected example by Keating et al. [39] reported the use of resin capture on a small solution model library (five individuals) produced by Ugi 4CC using a "convertible isocyanide (details for this library synthesis were given in the section on multiple-component condensations), as is described in Figure 15. A slight excess of the final cyclohexenamides was incubated with the support under anhydrous HC1/THF for 5 h at 55°C, then the resins were washed repeatedly and cleaved with 20% TFA in DCM for 20 min at room temperature. The cleavage solutions resulted to be the pure carboxylic acids (quantitative yields and >95% HPLC purities). 

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