Backbone amide linker (BAL) strategy for Nalpha-9-fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis of peptide aldehydes.
A rapid and efficient strategy has been developed for the general synthesis of complex peptide aldehydes. N(alpha)-Benzyloxycarbonylamino acids were converted to protected aldehyde building blocks for solid-phase synthesis in four steps and moderate overall yields. The aldehydes were protected as 1,3-dioxolanes except for one case where a dimethyl acetal was used. These protected amino aldehyde monomers were then incorporated onto 5-[(2 or 4)-formyl-3,5-dimethoxyphenoxy]butyryl-resin (BAL-PEG-PS) by reductive amination, following which the penultimate residue was introduced by HATU-mediated acylation. The resultant resin-bound dipeptide unit, anchored by a backbone amide linkage (BAL), was extended further by routine Fmoc chemistry procedures. Several model peptide aldehydes were prepared in good yields and purities. Some epimerization of the C-terminal residue occurred (10% to 25%), due to the intrinsic stereolability conferred by the aldehyde functional group, rather than any drawbacks to the synthesis procedure.
Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, USA.
Joseph C
JC
Kappel
George
G
Barany
D000447:Aldehydes / Q000138:chemical synthesis*; D000577:Amides / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005449:Fluorenes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000138:chemical synthesis*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000447:Aldehydes; D000577:Amides; D005449:Fluorenes; D010455:Peptides