Protecting orthogonal

In all cases examined the ( )-isomers of the allylic alcohols reacted satisfactorily in the asymmetric epoxidation step, whereas the epoxidations of the (Z)-isomers were intolerably slow or nonstereoselective. The eryfhro-isomers obtained from the ( )-allylic alcohols may, however, be epimerized in 95% yield to the more stable tlireo-isomers by treatment of the acetonides with potassium carbonate (6a). The competitive -elimination is suppressed by the acetonide protecting group because it maintains orthogonality between the enolate 7i-system and the 8-alkoxy group (cf the Baldwin rules, p. 316). 

An obvious outcome of the Hantzsch synthesis is the symmetrical nature of the dihydropyridines produced. A double protection strategy has been developed to address this issue. The protected chalcone 103 was reacted with an orthogonally protected ketoester to generate dihydropyridine 104. Selective deprotection of the ester at C3 could be accomplished and the resultant acid coupled with the appropriate amine. Iteration of this sequence with the C5 ester substituent ultimately gave rise to the unsymmetrical 1,4-dihydropyridine 105. 

A CONVENIENT PREPARATION OF AN ORTHOGONALLY PROTECTED C ,C -DISUBSTITUTED AMINO ACID ANALOG OF LYSINE l-tert-BUTYLOXYCARBONYL-4-((9-FLUORENYLMETHYLOXYCARBONYL)AMINO)-PIPERIDINE-4-... 

Since most aaAAs are hydrophobic in nature, peptides rich in aaAAs are generally restricted to study in organic solvents due to their low solubility in aqueous media. There have been very few examples of side-chain functionalized aaAAs that would allow for the synthesis of highly water-soluble peptides rich in aaAA content.3 This is primarily due to difficulty of synthesis, since side-chain functionalized derivatives must be orthogonally protected to allow for incorporation into solid-phase peptide synthesis. The harsh conditions, under which standard methods of aaAA synthesis are performed, make this a difficult task. 

The orthogonally-protected Cys moiety thus serves as a convenient handle that can be used to link aPNA modules together in order to expand its nucleic acid binding capability and/or attach molecular probes. 

Developments of protection strategies in peptide synthesis have led to the introduction of a wider variety of protecting groups for different functionalities and provide orthogonal protection to specific side chains (Table 1). 

Smith, J. J., Conrad, D. W., Cuneo, M. J. and Hellinga, H. W. (2005). Orthogonal site-specific protein modification by engineering reversible thiol protection mechanisms. Protein Sci. 14, 64-73. 

The large scale preparation of orthogonally protected pyrrole tricarboxylic acid derivatives (i.e., 92) was reported. A key step was the selective a-chlorination of a 2,4-dimethylpyrrole intermediate that was derived from the Knorr pyrrole synthesis. 

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