Macracyclic Peptides and Depsipeptides

Macrocyclic peptides and depsipeptides ( macrocyciic peptides with amide and ester linkages) are important natural compounds. They have been synthesized in low yield from open-chain precursors by DCC treatment at high dilution (E. SchrSder, 1963 M.M. Shemyakin, 

More successful are solid-phase methods in which the linear precursor is attached through a labile ester bond (e.g. o-nitrophenyl) to a polymer. 

First the protected oligopeptide is coupled with polymer-bound nitrophenol by DCC. N -Deblocking leads then to simultaneous cycliiation and detachment of the product from the polymer (M. Fridkin, 1965). Recent work indicates that high dilution in liquid-phase cycli-zation is only necessary, if the cyclization reaction is sterically hindered. Working at low temperatures and moderate dilution with moderately activated acid derivatives is the method of choice for the formation of macrocyclic lactams (R.F. Nutt, 1980). 

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