Selection of Protecting-Groups

In the tert-butoxycarbonyl (Boc) strategy for solid-phase peptide synthesis, cleavage from the solid-phase and side-chain deprotection is performed with strong acids such as hydrogen fluoride. Treatment of a glycopeptide with strong acid results in partial or, in most cases, complete cleavage 

FIGURE 15.3 0-Glycosides are cleaved by strong acids and 0-linked derivatives of serine and threonine undergo base-catalyzed -elimination. 

FIGURE 15.4 The Fmoc strategy, which relies on mild Fmoc cleavage with morpholine or piperidine, is commonly employed for synthesis of glycopeptides. 

SCHEME 15.1 Deacetylation of model glycopeptide 16 caused neither p-elimination nor epimerization of peptide stereocenters. Both types of side-reactions were, however, encountered under more drastic conditions often employed for removal of benzoyl groups. 

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The search for suitable protecting groups of carbonyl and hydroxyl functions has been of continuous importance in steroid chemistry. As a result of these efforts a good selection of protecting groups is now available for use in organic synthesis. 

The base lability of succinoyl diester hnker severely limits the selection of protecting groups available for an oligosaccharide synthesis, so a more versatile tether was required. Diether bonds of benzylphenol or dibenzyl of 1,4-di(hydroxymethyl)-benzene satisfy this requirement because they are stable to both bases and to acids. A sufficient acid stability is important since the formation of a glycosidic bond is an acid-catalyzed reaction, not surprisingly, as it is an acetal functionality. For instance, DOX,34 the dibenzyl hnker a,a -DiOxyXylyl diether, -0CH2C6H4CH20-, is not limited by restriction of the succinoyl hnker (1) when bound via a hydroxyl or as an... 

Corey EJ, Long AK, Greene TW, Miller JW. Computer-assisted synthetic analysis. Selection of protective groups for multistep organic syntheses. J Org Chem 1985 50 1920-1927. 

The success of a Merrifield synthesis is very strongly influenced by the selection of protecting groups to temporarily shield the terminal amino function and to permanently block side groups of trifunctional amino acids from undesired reactions. Even on polymeric phase, the strategy of a peptide synthesis is determined by the choice of the protecting groups. 

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