Hoeg-Jensen T, Spatola A F, Holm A
Chemistry Department, Royal Veterinary and Agricultural University, Frederiksberg, Denmark.
Int J Pept Protein Res. 1996 Mar;47(3):190-200. doi: 10.1111/j.1399-3011.1996.tb01344.x.
Peptides containing backbone thioamides (endothiopeptides) have been synthesized utilizing thioacylation under solid-phase conditions. The thioacylations were performed by activating N-protected amino monothio acids with the phosphorus-containing coupling reagent 6-nitrobenzotriazol-l-yloxytris(pyrrolidino)phosphoniu m hexafluorophosphate (PyNOP). This method avoids the use of P4S10-based O/S-exchange reagents, and it is thus amendable to amino acids with side-chain amides. Synthesis of endothio analogs of biologically active peptide such a 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 sequential position of its thioamide function. Compatibility of endothiopeptides with allylprotecting groups was studied, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was evaluated as a substitute for piperidine.
含有主链硫代酰胺的肽（内硫肽）已通过在固相条件下进行硫酰化反应合成。硫酰化反应通过用含磷偶联剂6-硝基苯并三唑-1-氧基三（吡咯烷基）磷六氟磷酸盐（PyNOP）活化N-保护的氨基单硫代酸来进行。该方法避免了使用基于P4S10的氧/硫交换试剂，因此适用于带有侧链酰胺的氨基酸。生物活性肽如pGlu-psi[CSNH]-His-Pro-NH2（TRH）和Leu-Gln-psi[CSNH]-Leu-Lys的内硫类似物的合成证明了这一特性。TRH类似物的质子和碳核磁共振光谱证实了其硫代酰胺官能团的序列位置。研究了内硫肽与烯丙基保护基团的相容性，并评估了1,8-二氮杂双环[5.4.0]十一碳-7-烯（DBU）作为哌啶的替代品。
