Side-chain protecting groups deprotection

The polymer-bound p-nitrobenzophenone oxime (71d) has been found to be a suitable support for stepwise peptide synthesis. Protected peptides can be assembled on 70d by coupling and deprotection steps similar to those employed in the usual Merrifield solid-phase procedures (Scheme 39). Cleavage of peptides from 71d can be accomplished with hydrazine and amino acid esters under mild conditions, which do not affect benzyl ester side-chain protecting groups. 

The combination of very mild coupling and deprotection protocols provides the flexibility needed in order to incorporate a variety of side-chain-protecting groups, cleavable by acid (Boc), base (Fmoc), Pd(II) (Aloc)J43 or nucleophiles (Dde)J441 Linear precursors of such templates with four orthogonally protected lysine residues are generally obtained in yields around 80% and cyclization proceeds quickly at high dilution almost quantitatively. 

In each step of the usual C-to-N peptide synthesis the N-protecting group of the newly coupled amino acid must be selectively removed under conditions that leave all side-chain protecting groups of the peptide intact. The most common protecting groups of side-chains (p. 229) are all stable towards 50% trifluoroacetic acid in dichloromethane, and this reagent is most commonly used for N"-deprotection. Only /erf-butyl esters and carbamates (=Boc) are solvolyzed in this mixture. 

Cleavage from solid support and deprotection of amino acids side chain protecting groups by TFA and suitable scavenger... 

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