Novel and facile solution-phase synthesis of 2,5-diketopiperazines and O-glycosylated analogs

Abstract

This work describes the synthesis in solution of a series of related diketopiperazines with potential biological activities: cyclo(l-Pro-l-Ser), cyclo(l-Phe-l-Ser), cyclo(d-Phe-l-Ser) and the corresponding glycosylated analogs of the latter, cyclo[d-Phe-l-Ser(αGlcNAc)] and cyclo[d-Phe-l-Ser(βGlcNAc)]. The synthetic approach involved coupling reactions of –OH or O-glycosylated serine benzyl esters with NFmoc-protected amino acids (Pro or Phe), followed by one-pot deprotection–cyclization reaction in the presence of 20% piperidine in DMF.