Solid Phase Methods

More successful are solid-phase methods in which the linear precursor is attached through a labile ester bond (e.g. o-nitrophenyl) to a polymer. 

Mernfield was awarded the 1984 Nobel Prize in chem istry for developing the solid phase method of pep tide synthesis... 

Solid phase peptide synthesis does not solve all purification problems however Even if every coupling step m the ribonuclease synthesis proceeded in 99% yield the product would be contaminated with many different peptides containing 123 ammo acids 122 ammo acids and so on Thus Memfield and Gutte s six weeks of synthesis was fol lowed by four months spent m purifying the final product The technique has since been refined to the point that yields at the 99% level and greater are achieved with current instrumentation and thousands of peptides and peptide analogs have been prepared by the solid phase method... 

Memfield s concept of a solid phase method for peptide synthesis and his devel opment of methods for carrying it out set the stage for an entirely new way to do chem ical reactions Solid phase synthesis has been extended to include numerous other classes of compounds and has helped spawn a whole new field called combinatorial chemistry Combinatorial synthesis allows a chemist using solid phase techniques to prepare hun dreds of related compounds (called libraries) at a time It is one of the most active areas of organic synthesis especially m the pharmaceutical industry... 

FIGURE 27 15 Peptide synthesis by the solid phase method Ammo acid residues are attached sequentially beginning at the C terminus... 

A new solid phase method to synthesize libraries of compounds based on 1,2,5-thiadiazolidine heterocycle was developed (00TL(41)3161). Starting from the coupling of the protected aminoacid to the resine functionalized with p-alkoxybenzylalcohol as the linker, a series of sulfahydantoins 251 could be obtained. The method is applicable to aminoacids with a basic side chain, aliphatic aldehydes or aldehydes with basic functionalities. 

Automated Peptide Synthesis The Merrifield Solid-Phase Method 1037... 

Peptide synthesis requires the use of selective protecting groups. An N-protected amino acid with a free carboxyl group is coupled to an O-protected amino acid with a free amino group in the presence of dicydohexvlcarbodi-imide (DCC). Amide formation occurs, the protecting groups are removed, and the sequence is repeated. Amines are usually protected as their teit-butoxy-carbonyl (Boc) derivatives, and acids are protected as esters. This synthetic sequence is often carried out by the Merrifield solid-phase method, in which the peptide is esterified to an insoluble polymeric support. 

Solid-Phase Methods for the Microwave-Assisted Synthesis of Heterocycles... 

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