Difficult macrocyclizations: new strategies for synthesizing highly strained cyclic tetrapeptides.
[reaction: see text] Cyclic tetrapeptides are an intriguing class of natural products. To synthesize highly strained cyclic tetrapeptides we developed a macrocyclization strategy that involves the inclusion of 2-hydroxy-6-nitrobenzyl (HnB) group at the N-terminus and in the "middle" of the sequence. The N-terminal auxiliary performs a ring closure/ring contraction role, and the backbone auxiliary promotes cis amide bonds to facilitate the otherwise difficult ring contraction. Following this route, the all-L cyclic tetrapeptide cyclo-[Tyr-Arg-Phe-Ala] was successfully prepared.
Meutermans
Wim D F
WD
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
Bourne
Gregory T
GT
Golding
Simon W
SW
Horton
Douglas A
DA
Campitelli
Marc R
MR
Craik
David
D
Scanlon
Martin
M
Smythe
Mark L
ML
D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D003500:Cyclization; D007536:Isomerism; D009578:Nitrobenzenes / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D010782:Photolysis; D011487:Protein Conformation
D000577:Amides; D009578:Nitrobenzenes; D009842:Oligopeptides; D010456:Peptides, Cyclic