Polyethylene glycol synthesis supports

Poly(ethylene glycol) supported liquid-phase syntheses by both the reaction of (polyethylene glycol (PEG))-supported imines with nitrile oxides, generated in situ from aldoximes, (300) and 1,3-dipolar cycloadditions of nitrile oxide, generated in situ on soluble polymers with a variety of imines (301, 302) have been described. The solid-phase synthesis of 1,2,4-oxadiazolines via cycloaddition of nitrile oxide generated in situ on solid support with imines has also been elaborated (303). These syntheses of 1,2,4-oxadiazolines provide a library of 1,2,4-oxadiazolines in good yields and purity. 

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... 

Barany, G., Alberido, F., Kates, S.A. and Kempe, M. (1997) Polyethylene glycol)-Containing Supports for Solid-Phase Synthesis of Peptides and Combinatorial Organic Libraries. In ACS Symposium Series 680. Polyethylene glycol) Chemistry and Biological Applications (eds J.M. Harris and S. Zalipsky), American Chemical Sodety, Washington, DC, pp. 239-64. 

SCHEME 22 Polyethylene glycol (PEG)-supported synthesis of benzimidazole-pyrrolo[l,2-a]-quinoxaline using Pictet-Spengler reaction rmder microwave conditions. 

Scheme 10.13. Polyethylene glycol)-supported domino synthesis of 1,2,3,4-tetrahydroquinolines.

Pillai, V.N.R., and Mutter, M. (1980) New, easily removable polyethylene glycol supports for liquid phase method of peptide synthesis./. Org. Chem. 45, 5364-5367. 

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

An efficient one-pot synthesis of isoxazolines, using soluble polymer-supported acrylate has been described (174). Thus, the addition of 1,4-benzenedicarbonitrile N,N -dioxide (generated from N, N -dihydroxy-1,4-benzenedicarboximidoy 1 dichloride) to polyethylene glycol-supported 2-propenoic acid 2-hydroxyethyl ester 32 (P = polyethylene glycol support) followed by cleavage of the bond with the support gave 3,3/-(l,4-phenylene)bis[4,5-dihydro-5-isoxazolecarboxylic acid] di-Me ester (33) in 97% yield. 

Scheme 4.69 Disaccharide synthesis on a soluble polyethylene glycol support.

It has long been recognized that polymeric supports for oligosaccharide synthesis do not need to be insoluble.33 Wang et al. applied the sulfoxide glycosylation method to the synthesis of disaccharide 79 (Scheme 3.14). The key feature of this work was the base-labile linker. Sulfoxide 74 was used to glycosylate polyethylene glycol... 

S Zalpsky, JL Chang, F Albericio, G Barany. Preparation and applications of polyethylene glycol-polystyrene graft resin supports for solid-phase peptide synthesis. Reactive Polymers 22, 243, 1994. 

S Kates, NA Sole, M Beyermann, G Barany, F Albericio. Optimized preparation of deca(L-alanyl)-L-valinamide by 9-fluorenylmethoxyloxycarbonyl (Fmoc) solid-phase synthesis on polyethylene glycol-polystyrene (PEG-PS) graft supports, with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) deprotection. Pept Res 9, 106, 1996. 

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... 

Soluble polymers that have been used in hquid-phase methodologies are listed in Fig. 5.1 [3, 7, 8, 34, 35]. Polyethylene glycol and non-cross-linked polystyrene are some of the most often used polymeric carriers for organic synthesis and have found frequent use in the preparation of soluble polymer-supported catalysts and reagents consequently, a brief discussion of these polymers is warranted. 

E. Garcia-Junceda, et al. Biocatalysis and Biotransformation 2000, 38, 271-281. MPEG consists of a polyethylene glycol 5000 monomethyl ester, see J.J. Kre-pinsky. Advances in polymer-supported solution synthesis of oligosaccharides, In Modern Methods in Carbohydrate Synthesis... 

Sauvagnat, B., Lamaty F., Lazaro, R. and Martinez, J., Polyethylene glycol (PEG) as polymeric support and phase-transfer catalyst in the soluble polymer liquid phase synthesis of ct-amino esters, Tetrahedron Lett., 1998, 39,821. 

Porcheddu, A., Ruda, G.F., Sega, A. and Taddei, M., Anew, rapid, general procedure for the synthesis of organic molecules supported on methoxy-polyethylene glycol (MeOPEG) under microwave irradiation conditions, Eur. J. Org. Chem., 2003, 907-912. 

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