The solid-phase synthesis of novel 14-membered macrocycles for high throughput screening.
A simple and efficient synthesis of novel 14-membered macrocycles from a resin-bound orthogonally protected lysine residue is described. Reductive alkylation of the lysine alpha-nitrogen introduces the first diversity element. Acylation of the resultant secondary amine with an Fmoc-amino acid introduces the second diversity element providing a resin-bound protected di-peptide precursor. Removal of the Fmoc-group is followed by acylation with a succinic anhydride to introduce the final diversity elements. Removal of the methyltrityl-group from the amino group followed by macrocyclization provides the desired macrocycles, after TFA cleavage, in excellent yield and purity.
Lanter
C L
CL
Hoechst Marion Roussel, Inc., Raritan, NJ 08869, USA.
Guiles
J W
JW
Rivero
R A
RA
D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D018629:Spectrometry, Mass, Secondary Ion; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D009841:Oligonucleotides; D010456:Peptides, Cyclic