Bidirectional macrocyclization of peptides by double multicomponent reactions.
Increasing the diversity of peptide cyclization methods is an effective way of accessing new types of macrocyclic chemotypes featuring a wide variety of ring sizes and topologies. Multicomponent reactions (MCRs) are processes capable of generating great levels of molecular diversity and complexity at low synthetic cost. In an attempt to further exploit MCRs in the field of cyclopeptides, we describe a bidirectional multicomponent approach for the synthesis of N-alkylated macrocyclic peptides of varied sequences and cross-linking positions. The process relies on the execution of two Ugi reactions between peptide diacids and diisocyanides. Varying the amino component enabled the installation of exocyclic elements of diversity, while skeletal diversity was created through different side chain and backbone cyclizations. This procedure shows prospects for the rapid scanning of the chemical space of macrocyclic peptides for applications in chemical biology and drug discovery.
Center for Natural Products Research, Faculty of Chemistry, University of Havana, Zapata y G, 10400, La Habana, Cuba. dgr@fq.uh.cu.
Manuel G
MG
Ricardo
Fidel E
FE
Morales
Hilda
H
Garay
Osvaldo
O
Reyes
Dimitar
D
Vasilev
Ludger A
LA
Wessjohann
Daniel G
DG
Rivera
D047028:Macrocyclic Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D047028:Macrocyclic Compounds; D010456:Peptides, Cyclic