A new bicyclic dipeptide isostere with pyrrolizidinone skeleton.
The synthesis of a new conformationally constrained Gly-(s-cis)Pro Turn Mimetic (GPTM) in both racemic and enantiomerically pure forms and their incorporation into peptides 18, 21, and 24 are reported. The synthetic strategy adopted to assemble the bicyclic pyrrolizidinone skeleton is based on the 1,3-dipolar cycloaddition of the cyclic nitrone 4a derived from proline and acrylamide, followed by a reductive cleavage/cyclization domino process. The enantiomerically pure GPTMs are obtained by synthesis and separation of diastereomeric intermediates containing (1R)-1-phenylethylamine as chiral auxiliary. Analysis of pseudotripeptides 18, 21, and 22 by FT-IR and NMR shows that the amide proton of GPTM derivatives 21 is intramolecularly hydrogen bonded in CDCl(3), while DMSO was shown to disrupt this hydrogen bond.
Cordero
Franca M
FM
Dipartimento di Chimica Organica Ugo Schiff, Università degli Studi di Firenze, via della Lastruccia 13, I-50019 Sesto Fiorentino, Florence, Italy. franca.cordero@unifi.it
Pisaneschi
Federica
F
Meschini Batista
Karina
K
Valenza
Silvia
S
Machetti
Fabrizio
F
Brandi
Alberto
A
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D011758:Pyrroles / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004151:Dipeptides; D011758:Pyrroles