94111-76-9Relevant academic research and scientific papers
Synthesis of constrained tetracyclic peptides by consecutive CEPS, CLIPS, and oxime ligation
Streefkerk, Dieuwertje E.,Schmidt, Marcel,Ippel, Johannes H.,Hackeng, Tilman M.,Nuijens, Timo,Timmerman, Peter,Van Maarseveen, Jan H.
, p. 2095 - 2100 (2019/04/11)
In Nature, multicyclic peptides constitute a versatile molecule class with various biological functions. For their pharmaceutical exploitation, chemical methodologies that enable selective consecutive macrocyclizations are required. We disclose a combination of enzymatic macrocyclization, CLIPS alkylation, and oxime ligation to prepare tetracyclic peptides. Five new small molecular scaffolds and differently sized model peptides featuring noncanonical amino acids were synthesized. Enzymatic macrocyclization, followed by one-pot scaffold-assisted cyclizations, yielded 21 tetracyclic peptides in a facile and robust manner.
General and Facile Route to Isomerically Pure Tricyclic Peptides Based on Templated Tandem CLIPS/CuAAC Cyclizations
Richelle, Gaston J. J.,Ori, Sumeet,Hiemstra, Henk,van Maarseveen, Jan H.,Timmerman, Peter
, p. 501 - 505 (2017/12/26)
We report a one-pot ligation/cyclization technology for the rapid and clean conversion of linear peptides into tricyclic peptides that is based on using tetravalent scaffolds containing two benzyl bromide and two alkyne moieties. These react via CLIPS/CuAAC reactions with cysteines and azides in the peptide. Flexibility in the scaffolds is key to the formation of isomerically pure products as the flexible scaffolds T41 and T42 mostly promote the formation of single isomeric tricycles while the rigid scaffolds T43 and T44 do not yield clean products. There seems to be no limitation to the number and types of amino acids present as 18 canonical amino acids were successfully implemented. We also observed that azides at the peptide termini and cysteine residues in the center gave better results than compounds with the functional groups placed the other way round.
Synthesis and Characterization of Blocked and Ligand-Appended Hemes Derived from Atropisomeric meso-Diphenylporphyrins
Young, Richard,Chang, C. K.
, p. 898 - 909 (2007/10/02)
The synthesis of a series of sterically blocked and imidazole-appended meso-diphenyletioporphyrins is described.These hybrid porphyrins have good solubility and spectroscopic properties of β-substituted porphyrins as well as the orientation specificity of ortho-position-derivatized tetraphenylporphyrins.The effectiveness of the blocking groups is demonstrated by ferric hemin hydroxide formation in the doubly protected trans-5,15-bis-2,8,12,18-tetraethyl-3,7,13,17-tetramethylporphine, characterized by UV-visible, 1H NMR, and IR spectra and cyclic voltammetry.The advantage of the m-benzyl linkage in enforcing imidazole coordination to ferric hemes is demonstrated by 1H NMR studies on various type of imidazole-appended heme complexes.Several potential binucleating systems have also been prepared by incorporating nonheme chelating ligands to the hybrid porphyrins.
