Polymer-supported synthesis, soluble

Chemistry on soluble polymer matrices has recently emerged as a viable alternative to solid-phase organic synthesis (SPOS) involving insoluble cross-linked polymer supports. Separation of the functionalized matrix is achieved by solvent or heat precipitation, membrane filtration, or size-exclusion chromatography. Suitable soluble polymers for liquid phase synthesis should be crystalline at room temperature, with functional groups on terminal ends or side chains, but must not be not cross-linked they are therefore soluble in several organic solvents. 

In a related study, a Schiff base-protected glycine was reacted with a variety of electrophiles under the action of microwave irradiation [73]. No extra solvent was necessary to perform these reactions because PEG played the role of polymeric support, solvent, and PTC. The best results were obtained by using cesium carbo- 

A method for microwave-assisted transesterifications has been published [74]. The microwave-mediated derivatization of poly(styrene-co-allyl alcohol) was investigated as key step in the polymer-assisted synthesis of heterocycles. The procedure was applied to several j8-ketoesters and multigram quantities of products were obtained when neat mixtures of the reagents in open vessels were exposed to micro-wave irradiation in a domestic microwave oven. The soluble supports obtained were used for preparation of a variety of bicyclic heterocycles, for example pyrazo-lopyridinediones or coumarins. 

10 min under the action of microwave irradiation in a methanolic solution of sodium bicarbonate (NaHCOs). 

A closely related study led to microwave-assisted liquid-phase synthesis of chiral quinoxalmes [81]. A variety of L-a-amino acid methyl ester hydrochlorides were coupled to MeO-PEG-bound ortho-fluoronitrobenzene by the already described ipso-fluoro displacement. Reduction under the action of microwave irradiation resulted in spontaneous synchronous intramolecular cyclization to the corresponding 1,2,3,4-tetrahydroquinoxalin-2 -ones. 

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Initially, the term Hquid-phase synthesis was used to contrast the differences between soHd-phase peptide synthesis and a method of synthesis on soluble polyethylene glycol (PEG) [5, 6]. Although soluble polymer-supported synthesis is less ambiguous than Hquid-phase synthesis, the latter term is more prevalent in the Hterature. In-keeping with previous reviews [7-12], the phrases classical or solution synthesis will be used to describe homogeneous reaction schemes that do not employ polymer supports while liquid-phase synthesis will be reserved... 

Shey, J.-Y. Sun, C.-M. Soluble Polymer-Supported Synthesis of N,N-di(Boc)-Protected Guanidines, Synlett 1998, 1423-1425. 

Sauvagnat, B., Kulig, K., Lamaty, E, Lazaro, R. and Martinez, J., Soluble polymer supported synthesis of a-amino acid derivatives, /. Comb. Chem., 2000, 2, 134. 

Xia, M., Wang, Y.-G. Soluble polymer-supported synthesis of Biginelli compounds. Tetrahedron Lett. 2002, 43, 7703-7705. 

Soluble polymer supported synthesis and transformations of heterocycles 00ACR546. 

The l,2,3,4-tetrahydro-j8-carboline pharmacophore is an important structural element in several tryptophan-derived natural product alkaloids. A soluble polymer supported synthesis of l,2,3,4-tetrahydro-j8-carboline derivatives was reported by Wu and Sung. The one-pot condensation of Fmoc-protected tryptophan anchored to MeO-PEG-OH via an ester linkage has been performed with a variety of aldehydes and ketones under the action of microwave irradiation to provide immobilized l,2,3,4-tetrahydro-yS-carboline derivatives these were liberated from the soluble matrix in good yield and high purity [123]. 

The combination of soluble polymer-supported synthesis with MW technology provided a highly versatile platform for the generation of chiral quinoxalin-2-one libraries. A simple work-up and cleaner products were achieved compared with... 

Lee, K.J. et al., Soluble-polymer supported synthesis of a prostanoid library identification of antiviral activity, Org. Lett., 1, 1859, 1999. 

Although solid-phase synthesis is frequently linked to combinatorial chemistry, this is not a requirement. Other synthetic methodologies, such as solution-phase synthesis and soluble polymer-supported synthesis, have also been used to effect the combinatorial synthesis process. However, solid-phase synthesis allows the most efficient combinatorial synthesis. The advantages and problems with solid-supported synthesis are described in later chapters. Thus, combinatorial chemistry is not solid-phase chemistry, albeit combinatorial chemistry can be advantageously performed on the solid phase. 

Ito and coworkers have combined the soluble polymer-supported synthesis with the catch-and-release protocol using the chloroacetyl (ClAc) tag (Scheme 16.20). Glucosamine acceptor bound to a low molecular weight polyethylene glycol (PEG) 70 was glycosylated with a thiogalactoside donor 71 in the presence of dimethyl(methylthio) sulfonium triflate (DMTST) in CH2CI2 to provide the disaccharide 72 in 94% yield. 

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