21612-32-8Relevant articles and documents
Fine-tuning the balance between peptide thioester cyclization and racemization
Popovic, Stanimir,Wijsman, Linda,Landman, Iris R.,Sangster, Maaike F.,Pastoors, Dorien,Veldhorst, Berend B.,Hiemstra, Henk,Van Maarseveen, Jan H.
supporting information, p. 443 - 446 (2016/02/18)
Ring-closure towards seven-membered bislactams containing an α-amino acid and β-alanine is problematic. Such difficult lactamizations are accompanied by side-reactions such as hydrolysis, oligomerization and racemization. By starting from linear peptide 4-methoxythiophenol esters, dilution to 1 mM in combination with phosphate buffer (pH 6.8) intermolecular reactions and racemization could be largely suppressed. Thioesters with the chiral residue at the C-terminus gave the bislactams in yields up to 60 % and enantiomeric excess up to 99 %. Enantiopure bislactams were obtained exclusively from the reversed sequence bearing β-alanine at the C-terminus. Straightforward and efficient synthesis of enantiopure homodiketopiperazines was achieved from linear peptide thioesters in aqueous buffered medium by direct cyclization. This method is characterized by the simplicity of the synthetic procedure, the use of commercially available amino acids, and, finally, the fact that synthetically demanding auxiliaries are not required for this otherwise difficult cyclization.
