Of indolyl diketopiperazines

Diketopiperazine formation has long been described as a side reaction in peptide synthesis. It occurs after deprotection or neutralization of the oc-amino group at the dipeptide stage and reduces the overall yield of the synthesis. However, diketopiperazine structures have also been found in natural products with therapeutic properties and hence they have been used as a scaffolds to design new potential drugs [38, 91, 92]. A typical example would be the synthesis of indolyl diketopiperazine alkaloids. Access to these compounds may be achieved by Pictet-Spengler reaction of L-tryptophan bound to hydroxymethylpolystyrene resin with aldehydes. Fmoc amino acids were then coupled and final Fmoc deprotection resulted in cyclative release to yield alkaloids in 50-99% yields (Figure 15.9) [93, 94],... 

Schinkel, A.H., and Koomen, G.J. (2001) Inhibition of BCRP-mediated drug efflux by fumitremorgin-type indolyl diketopiperazines. Bioorganic Medicinal Chemistry Letters, 11, 29—32. 

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