Cyclic Peptides with a Diversely Substituted Guanidine Bridge: Solid‐Phase Synthesis and Structural Analysis

Abstract

The systems formed by palladium acetate [Pd(OAc)2] and hybrid silica materials prepared by sol‐gel from monosilylated imidazolium and disilylated dihydroimidazolium salts show catalytic activity in Suzuki–Miyaura cross‐couplings with challenging aryl bromides and chlorides. They are very efficient as recoverable catalysts with aryl bromides. Recycling is also possible with aryl chlorides, although with lower conversions. In situ formation of palladium nanoparticles has been observed in recycling experiments.

Cyclic Enkephalins with a Diversely Substituted Guanidine Bridge or a Thiourea Bridge: Synthesis, Biological and Structural Evaluations

“…Taken together, these results indicated that the most significant variations in binding affinity and selectivity were observed in the small cycle series, most likely because of their lower global conformational freedom, which resulted in a higher impact of guanidine bridge substitution on peptide conformation, as previously shown. 1 The smaller cycle size also afforded the more potent compounds.…”

“…1 One nitrogen of the guanidine group is extracyclic and can be non-, mono-, or disubstituted. A solid phase synthetic methodology was developed to prepare diversely substituted analogues of a single peptide sequence from a thiourea bridged intermediate via a S -methylation step.…”

Blood–brain transfer and antinociception of linear and cyclic N-methyl-guanidine and thiourea-enkephalins

“…The synthesis of the two cyclic enkephalin analogs, CycS and CycNMe, was performed on solid phase and is published in detail elsewhere [51,52]. Another solid phase synthetic strategy, according to the synthesis of N-mono-and di-alkylated-arginine containing compounds, was used for the synthesis of the two linear enkephalin analogs LinS and LinNMe [33].…”

“…Another solid phase synthetic strategy, according to the synthesis of N-mono-and di-alkylated-arginine containing compounds, was used for the synthesis of the two linear enkephalin analogs LinS and LinNMe [33]. The protected peptide Boc-Tyr(tBu)-D-Ala-Gly-Phe-Dap(Alloc) was first assembled by manual solid-phase synthesis on a Rink amide PS resin following Fmoc chemistry with HBTU/DIEA as coupling agents [51,52]. After peptide assembly, the Alloc group was removed by treatment of the resin with Pd[PPh 3 ] 4 (0.2 equiv.)…”

“…As such, peptide cyclization is a recognized and powerful tool of peptide chemistry for generating analogs with improved pharmacokinetic properties [37]. Recently, a structural study and synthesis of a new kind of cyclic peptides, which incorporated either a thiourea bridge or a Nalkyl substituted guanidine bridge, have been reported [52]. This approach has been applied for the first time to enkephalins, yielding analogs with nanomolar affinity and moderate selectivity towards the -opioid receptor [51].…”