Protecting orthogonality

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). 

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. 

We have demonstrated an orthogonal protection/deprotection strategy for preparing a carbohydrate core that could be iteratively deprotected and glycosylated to form... 

Scheme 11.10 Application of an orthogonal protection/deprotection strategy in preparation of a tetrasaccharide.

Scheme 11.11 A structure formed using a one-pot method with orthogonal protecting groups.

F Albericio. Orthogonal protecting groups for V-amino and C-terminal carboxyl functions in solid-phase peptide synthesis. Biopolymers (Pept Sci) 55, 123-139, 2000. 

Fig. 4. Schematic representation of template-assembled synthetic proteins. The conforma-tionally restricted template can be orthogonally protected and sequentially linked to helical segments to form a large variety of functionalized TASP proteins. Flexible spacers that connect the folded peptide segments and the template provide the necessary conformational freedom that will allow the hydrophobic residues to find their optimum orientations for packing the core...

Kukula H,Veit S, Godt A (1999) Eur J Org Chem 277 Synthesis of monodisperse oligo-PEs using orthogonal protecting groups with different polarity for terminal acetylene units... 

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