Options for Minimizing Epimerization during the Coupling of Segments

22 OPTIONS FOR MINIMIZING EPIMERIZATION DURING THE COUPLING OF SEGMENTS 

The danger of epimerization during the coupling of segments exists for all cases, except when me activated residue is Pro and Gly, with a few exceptions (see Section 7.23). The obvious is to design a strategy mat involves activation at these residues only. Options to try to minimize me side reaction for activation at other residues are as follows  

Devise a strategy mat avoids activation at me more sensitive residues such as Val, He, Thr(Pg), His(Pg), and Arg(Pg) (Pg = protecting group see Section 4.16). 

Use an apolar solvent (see Section 4.12), though most of me time mis is not possible because of me limited solubility of compounds in these solvents. 

Use me acyl-azide method of coupling (see Sections 2.13 and 7.16) with particular care to avoid contact of me azide with tertiary amine. 

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