AMINO MONOTHIO ACIDS IN SOLID-PHASE SYNTHESIS OF PEPTIDE THIOAMIDES

Peptides containing backbone thioamides (endothiopeptides) have been s ynthesized utilizing thioacylation under solid-phase conditions. The t hioacylations were performed by activating N-protected amino monothio acids with the phosphorus-containing coupling reagent robenzotriazol-1 -yloxytris(pyrrolidino)phosphonium hexafluorophosphate (PyNOP). This m ethod avoids the use of P4S10-based O/S-exchange reagents, and it is t hus amendable to amino acids with side-chain amides. Synthesis of endo thio analogs of biologically active peptide such as pGlu-psi[CSNH]-His -Pro-NH2 (TRH) and Leu-Gln-psi[CSNH]-Leu-Lys demonstrated this feature . Proton and carbon NMR spectra of the TRH analog verified the sequent ial position of its thioamide function. Compatibility of endothiopepti des with allyl-protecting groups was studied, and 1,8-diazabicyclo[5.4 .0]undec-7-ene (DBU) was evaluated as a substitute for piperidine. (C) Munksgaard 1996.