Synthesis of constrained bicyclic dipeptide mimetics

Bicyclic Tripeptide Mimetics with Reverse Turn Inducing Properties

“…14,[19][20][21][22] BTD and the related 4,5-bicyclic, 5,5-bicyclic, 7,5-bicyclic, and 7,6-bicyclic core structures are most frequently synthesized by reaction sequences where ring closure by intramolecular N-acylation constitutes the last step. [23][24][25] While numerous investigations have been devoted to constrained bicyclic dipeptides, 24 studies of the corresponding bicyclic tripeptides are rare. Access to reliable methods that, on solid phase, allow for construction of well-defined constrained tripeptide units and that constitute a complement to the commonly used disulfide-based cyclization procedures is highly desirable.…”

“…Several cyclic and bicyclic dipeptide analogues intended to stabilize the peptide in a reverse turn have been reported. − Among these, the 5,5-bicyclic dipeptidomimetic 1 was designed as a type II β-turn mimetic and the 6,5-bicyclic dipeptidomimetic BTD 2 as a type II‘ β-turn mimetic (Chart ). BTD has been extensively studied and used for diverse biological applications. ,− BTD and the related 4,5-bicyclic, 5,5-bicyclic, 7,5-bicyclic, and 7,6-bicyclic core structures are most frequently synthesized by reaction sequences where ring closure by intramolecular N-acylation constitutes the last step. − While numerous investigations have been devoted to constrained bicyclic dipeptides, studies of the corresponding bicyclic tripeptides are rare. Access to reliable methods that, on solid phase, allow for construction of well-defined constrained tripeptide units and that constitute a complement to the commonly used disulfide-based cyclization procedures is highly desirable.…”

Vinyl Sulfide Cyclized Analogues of Angiotensin II with High Affinity and Full Agonist Activity at the AT1Receptor

“…ω-Formyl-R-amino acids have frequently been used for the construction of bicyclic thiazabicycloalkane dipeptide units. [56][57][58][59][60] The thiazabicycloalkanes are most often synthesized through reaction of the formyl function of the ω-formyl-R-amino acid with a neighboring nitrogen and sulfur atom, followed by intramolecular N-acylation to give bicyclization and to provide a thiazolidine in the final step. We previously reported a spontaneous bicyclization, which delivered tripeptide mimetic thiazabicycloalkanes upon deprotection of octapeptides encompassing masked ω-formyl-R-amino acids.…”

Design, synthesis, and application of azabicyclo[X.Y.0]alkanone amino acids as constrained dipeptide surrogates and peptide mimics

“…5‐Thiaindolizidinone amino esters 297 possessing a sulfur atom in the lactam ring have been synthesized by coupling L ‐glutamate γ‐dimethyl acetal 295 and D ‐ S ‐( tert ‐butyl)‐ N ‐(phthalimido) cysteine to give dipeptide 296 (Scheme ) 73. Both, (6 R )‐ and (6 S )‐thiaindolizidinone phthalimido esters 297 were obtained diastereoselectively (d.r.…”