Systematic study of the synthesis of macrocyclic dipeptide beta-turn mimics possessing 8-, 9-, and 10- membered rings by ring-closing metathesis.
[structures: see text] A systematic study was performed to establish general synthesis protocols for forming enantiomerically pure macrocyclic dipeptide lactams. Focusing on macrocycles of 8-, 9-, and 10-membered rings, effective syntheses were achieved by a sequence featuring peptide coupling of allyl- and homoallyl-glycine building blocks followed by ring-closing metathesis. The 8-membered lactam-possessing cis-amide and cis-olefin geometry as well as 9-membered [corrected] lactams having trans-amide and cis-olefin [corrected] configurations were effectively prepared by a general strategy employing the respective protected dipeptide, the first generation Grubbs' catalyst, and temporary protection of the central amide as a benzyl derivative. The 10-membered macrocycle was synthesized possessing cis- or trans-olefin geometry by employing similar metathesis conditions in the presence or absence of temporary benzyl amide protection, respectively [corrected]
Kaul
Ramesh
R
Département de Chimie, Université de Montréal, C.P. 6128, Succursale Centre Ville, Montréal, Québec, Canada H3C 3J7.
Surprenant
Simon
S
Lubell
William D
WD
D032701:Biomimetics; D003500:Cyclization; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
D004151:Dipeptides; D047029:Lactams, Macrocyclic; D010456:Peptides, Cyclic