UPS on Weinreb resin: a facile solid-phase route to aldehyde and ketone derivatives of "unnatural" amino acids and peptides.
The solid-phase synthesis of "unnatural" amino aldehydes, amino ketones, peptide aldehydes, and peptide ketones was accomplished from commercially available resin in a series of room temperature reactions. The initial step involved addition of an "unnatural" side chain to the N-terminus of a benzophenone imine-activated Weinreb resin-bound amino acid or peptide derivative. The alkylated imine was hydrolyzed, and the amine was converted to the Boc-, Cbz-, or naphthoyl derivative. The resin-bound substrate was then cleaved with DIBAL-H or a Grignard reagent to give the amino aldehyde, amino ketone, peptide aldehyde, or peptide ketone products. Twenty-four reactions were carried out simultaneously using a "Billboard" reaction apparatus to give products in 27-87% (59% average) isolated yield.
O'Donnell
M J
MJ
Department of Chemistry, Indiana University-Purdue University at Indianapolis 46202, USA. odonnell@chem.iupui.edu
Drew
M D
MD
Pottorf
R S
RS
Scott
W L
WL
D000215:Acylation; D000447:Aldehydes / Q000138:chemical synthesis*; D000478:Alkylation; D000596:Amino Acids / Q000138:chemical synthesis*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D007202:Indicators and Reagents; D007659:Ketones / Q000138:chemical synthesis*; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis*
D000447:Aldehydes; D000596:Amino Acids; D003432:Cross-Linking Reagents; D007202:Indicators and Reagents; D007659:Ketones; D019151:Peptide Library; D010455:Peptides