Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India.
J Org Chem. 2021 Dec 17;86(24):17667-17672. doi: 10.1021/acs.joc.1c01906. Epub 2021 Nov 25.
Peptide drugs bradykinin, a leuprolide analogue, 2(PZ-128), and rapastinel are synthesized in 56-77% yield using heating-assisted liquid-phase peptide synthesis on a soluble polynorbornene support. These drugs of commercial utility and complex structures are obtained in 2-5.5 h with no epimerization and >95% purity using only 1.2 equivalents of amino acids and coupling reagents. The peptide yield and purity are comparable or superior to the reported methods.
多肽药物缓激肽、亮丙瑞林类似物 2(PZ-128)和拉帕司汀采用可溶聚降冰片烯支持物,通过加热辅助的液相肽合成,以 56-77%的产率合成。这些具有商业实用性和复杂结构的药物在 2-5.5 小时内得到,仅使用 1.2 当量的氨基酸和偶联试剂,无消旋化,且>95%的纯度。与报道的方法相比,该方法的多肽产率和纯度相当或更优。