High-Loading Resins

Swali, V., Wells, N.J., Langley, G.J., and Bradley, M. (1997) Solid-phase dendrimer synthesis and the generation of super-high-loading resin beads for combinatorial chemistry. J. Org. Chem. 62, 4902-4903. 

After isolating the product of a solid phase synthesis, the support (resin + linker) is usually discarded as waste, although successful examples of its reuse in further synthetic cycles are known with trityl type linkers (Frechet and Haque 1975). To reduce both volume of operation and amount of waste, the loading of the resin (quantified as millimoles of functionality per gram) has to be increased. Besides theoretical limitations (for polystyrene this is reached when every phenyl ring is substituted by the linker), there may be practical boundaries for using highly loaded resins in solid-phase supported synthesis. This issue was studied... 

Example 5. Optimization of the Polymer Support Highly Loading Resins for Polymer-Supported Reagents44... 

Fromont, C., Bradley, M. High-Loading Resin Beads for Solid Phase Synthesis Using Triple Branching Symmetrical Dendrimers. Chem. Commun. 2000, 283-284. 

Some linkers, such as Rink amide linker, are sold A-Fmoc protected. The first removal of the Fmoc group may require a longer deprotection time particular with highly loaded resin (>0.9 mmol/g). In these cases it should be useful to repeat steps 2 and 3 of Protocol 7. 

Figure 11 Slope-fitting analysis for estimate of the composition of copper(II)-chloride complexes in the anion-exchanger phase at high loading resin (50-100 mesh, Cl form) A Dowex 1-Xl, B AG 1-X8 C Dowex 1-X16 solution CuClj + 6 M HCl. (From Ref. 10.)...

Fig. 15.4.61. Gel phase NMR spectrum of peptide synthesised on a high load resin with the matrix swollen in ( 03)280 (see Ref. 101).

While all the above methods have been used very successfully on standard laboratory scale, they also have significant potential for rapid synthesis on medium scale (up to several kg) and possibly even larger. High-loading resins can bind an equal weight of substrate and so are efficient in terms of volume. ... 

Oxidizing and Reducing Agents 4.3.1.7 High-Loading Resins... 

Coantic S, Subra G, Martinez J (2008) Microwave-assisted solid phase peptide synthesis on high loaded resins. Int J Pept Res Ther 14 143-147... 

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