Diastereoselective Pictet-Spengler approach for the synthesis of pyrrolo[3,2-e][1,4]diazepin-2-one peptide turn mimics.
Sixteen pyrrolo[3,2- e][1,4]diazepin-2-ones 1 were synthesized in 4-5 steps and 5-48% overall yields from 4-oxoproline 8 by a route featuring a diastereoselective Pictet-Spengler reaction to close the seven-membered diazepinone ring. Crystallographic analysis of pyrrolo[3,2- e][1,4]diazepin-2-one 1b by X-ray diffraction demonstrated that the alpha-amino acid residue adopted dihedral angle geometry similar to an ideal gamma-turn, illustrating the potential for employing these novel heterocycles as peptide turn mimics.
Département de chimie, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, Québec, Canada, H3C 3J7.
Philippe
P
Deaudelin
William D
WD
Lubell
D000475:Alkenes / Q000737:chemistry; D000577:Amides / Q000737:chemistry; D000586:Amination; D001381:Azepines / Q000737:chemistry*; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*; D013237:Stereoisomerism
D000475:Alkenes; D000577:Amides; D001381:Azepines; D010455:Peptides; D011758:Pyrroles