Blocking of Side Chain Amino Groups

More recently tert.butyl pyrocarbonate, usually described as tert.butyl carbonic anhydride, gained considerable popularity, mainly because the products formed during introduction of the Boc group, are harmless and easily removed  

The methods discussed here are applicable for the incorporation of other urethane-type blocking groups as well. In some cases the old chloride method prevails. For instance 9-fluorenylmethyl chlorocarbonate, a stable crystalline solid, allows smooth introduction of the Fmoc group. 

In a sense this is a perfect example of orthogonal protection schemes in which two different chemical reactions are applied, one for the removal of the transient and the other for the cleavage of the semipermanent blocking groups. Unfortunately this combination can not be readily utilized in the synthesis of peptides with sulfur containing amino acid residues poisoning of the catalyst impedes the process. It is possible to employ countermeasures, such as addition of base or the use of liquid ammonia as solvent, when methionine residues are the source of difficulties, but cysteine residues present a less readily surmountable obstacle. 

Application of these groups in the opposite sense, that is the Z group for side chain protection of lysine residues and the Boc group for the transient masking of the a-amino group, is more generally applicable. 

An alternative way to enhance selectivity in the removal of two different blocking groups is to increase the sensitivity of one of them toward acids. This thought led to the development of the already mentioned biphenylylisopropyl-oxycarbonyl (Bpoc) group and to the application of the highly acid sensitive triphenylmethyl (trityl) group. 

---