Semipermanent blocking

In a sense this is a perfect example of orthogonal protection schemes in which two different chemical reactions are applied, one for the removal of the transient and the other for the cleavage of the semipermanent blocking groups. Unfortunately this combination can not be readily utilized in the synthesis of peptides with sulfur containing amino acid residues poisoning of the catalyst impedes the process. It is possible to employ countermeasures, such as addition of base or the use of liquid ammonia as solvent, when methionine residues are the source of difficulties, but cysteine residues present a less readily surmountable obstacle. 

The general approach for carboxyl protection is esterification. The simplest solution, the use of methyl or ethyl esters, is suitable for semipermanent blocking, although the commonly applied process of unmasking, alkaline hydrolysis, is far from unequivocal. It is accompanied by racemization, partial hydrolysis of carboxamide groups in the side chain of asparagine and glutamine residues and by several other side reactions which are initiated by proton abstraction (Cf. Chapter VII). Nevertheless, perhaps because of the attractively simple esterification of amino acids... 

The semipermanent blocking selected for this purpose is protection of the C-terminal carboxyl group in the form of picolyl esters. 4-Hydroxymethyl-... 

Contents Introduction. - Activation and Coupling. - Reversible Blocking of Amino and Carboxyl Groups. - Semipermanent Protection of Side Chain Functions. - Side Reactions in Peptide Synthesis. - Tactics and Strategy in Peptide Synthesis. - Techniques for the Facilitation of Peptide Synthesis. - Recent Developments and Perspectives. - Author Index. - Subject Index. 

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