A synthetic strategy for the preparation of cyclic peptide mimetics based on SET-promoted photocyclization processes.
A novel method for the synthesis of cyclic peptide analogues has been developed. The general approach relies on the use of SET-promoted photocyclization reactions of peptides that contain N-terminal phthalimides as light absorbing electron acceptor moieties and C-terminal alpha-amidosilane or alpha-amidocarboxylate centers. Prototypical substrates are prepared by coupling preformed peptides with the acid chloride of N-phthalimidoglycine. Irradiation of these substrates results in the generation of cyclic peptide analogues in modest to good yields. The chemical efficiencies of these processes are not significantly affected by (1) the lengths of the peptide chains separating the phthalimide and alpha-amidosilane or alpha-amidocarboxylate centers and (2) the nature of the penultimate cation radical alpha-heterolytic fragmentation process (i.e., desilylation vs decarboxylation). An evaluation of the effects of N-alkyl substitution on the amide residues in the peptide chain showed that N-alkyl substitution does not have a major impact on the efficiencies of the photocyclization reactions but that it profoundly increases the stability of the cyclic peptide.
Yoon
Ung Chan
UC
Department of Chemistry, College of Natural Sciences, Pusan National University, Pusan 609-735, Korea.
Jin
Ying Xue
YX
Oh
Sun Wha
SW
Park
Chan Hyo
CH
Park
Jong Hoon
JH
Campana
Charles F
CF
Cai
Xiaolu
X
Duesler
Eileen N
EN
Mariano
Patrick S
PS
D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D010777:Photochemistry; D010797:Phthalimides / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation
D010456:Peptides, Cyclic; D010797:Phthalimides