Protection of the a-amino group

The efficiency of this method was demonstrated by the elegant two-step synthesis of aspartame [87], Protection of the a-amino group and activation of the a-carboxylic group are accomplished in only one step Deprotection of the amino functionality occurs during aminolysis, such as with methyl phenylalaninate (H-Phe-OMe in equation 15)... 

Benzyl carbamate protection (Cbz or Z group see Table 10.15) was initially chosen by Merrifield for solid-phase peptide synthesis [255], The strongly acidic conditions required for its solvolysis (30% HBr in AcOH, 25 °C, 5 h) demanded the use of an acid-resistant nitrobenzyl alcohol linker. Z-protection of the a-amino group in solid-phase peptide synthesis was, however, quickly abandoned and replaced by the more acid-labile Boc protection. Benzyl carbamates can be cleaved by strongly ionizing... 

This unexpected consequence of the efficient reaction of carbon dioxide can be expressed in an other way NCAs can be considered as the most activated amino acid species achievable in water in the environment of the primitive Earth. The only exception would be species bearing a chemical protection of the a-amino groups that are unlikely because peptide elongation would have been complicated by the necessity of an additional deprotection step. From a prebiotic perspective, there is consequently no need to search for activated amino acid derivatives with a degree of activation higher than NCAs (thermodynamic limit in Fig. 3). 

A comparative kinetic analysis of the rate of guanidinylation of benzylamine with 1,3-bis(benzyloxycarbonyl)- or l,3-bis(teri-butoxycarbonyl)-2-triflylguanidinet with the rates of those reagents discussed in Sections 2.6.1.6.1 and 2.6.1.6.2 clearly indicated that the triflyl derivatives are the most powerful reagents (Figure l),f l well-suited for guanidinylation of simple amino acid derivatives as well as of peptides in solution or linked to resins.In the latter case, a selective protection of the A -amino group of the ornithine residues is required. 

The Aloe group can be used for protection of the a-amino group instead of Boc or Fmoc as it is orthogonal to the semipermanent benzyl- or ferf-butyl-type side-chain and linker protections. This Aloe protection can be useful when some features of the peptide or pseudopeptide prevent the use of bases or acids in the deprotection step. In model studies, pseu-dometaUic hydrides (tributyltin hydride and borane-dimethylamine complex), which are neutral reagents, have been used as aUyl scavengers. 

Originally, the photoremovable 4,5-dimethyl-2-nitrobenzyloxycarbonyl group (Nvoc, 3) introduced by Patchornik (Scheme 3)bl was utilized for temporary protection of the a-amino group of the growing peptide chain. However, photolysis under optimized conditions (12 min in 5 mM sulfuric acid/dioxane) sometimes causes side reactions and does not always proceed quantitatively. 

Both aromatic and aliphatic isocyanides including a-isocyanoacetate provided a-ketoamides with moderate to good yields. However, the sterically hindered tert-butyl isocyanide provided the coupling product in low yield. Ahphatic aldehydes including functionalized ones are effective substrates. With a-amino aldehyde, N,N-double protection of the a-amino group was crucial for the reaction to occur properly. Chiral aldehyde 110 has been efficiently transformed into the corresponding... 

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