ABSTRACT
The peptide coupling reactions allowing the incorporation of trifluoromethyl substituted oxazolidine-type pseudoprolines (CF3-ΨPro) into peptide chains have been studied. While standard protocols can be used for the peptide coupling reaction at the C-terminal position of the CF3-ΨPro, acid chloride activation has to be used for the peptide coupling reaction at the N-terminal position to overcome the decrease of nucleophilicity of the CF3-ΨPro. We demonstrate that the N-amidification of a diastereomeric mixture of CF3-ΨPro using Fmoc-protected amino acid chloride without base gave the corresponding dipeptides as a single diastereomer (6 examples). The ratio of the cis and trans amide bond conformers was determined by NMR study, highlighting the role of the Xaa side chains in the control of the peptide backbone conformation. Finally a tripeptide bearing a central CF3-ΨPro has been successfully synthesized.
Subject(s)
Amino Acids/chemistry , Fluorocarbons/chemistry , Peptides/chemistry , Proline/analogs & derivatives , Thiazoles/chemistry , Amides/chemistry , Magnetic Resonance Spectroscopy , Molecular Conformation , Proline/chemistryABSTRACT
An efficient iodocyclization reaction of a chiral Tfm-allylmorpholinone provides a straightforward route to alpha-Tfm-prolines and alpha-Tfm-dihydroxyprolines. The methodologies developed are particularly well adapted for gram-scale synthesis of enantiopure compounds.
Subject(s)
Fluorocarbons/chemistry , Morpholines/chemistry , Proline/analogs & derivatives , Proline/chemical synthesis , Crystallography, X-Ray , Cyclization , Models, Molecular , Molecular Conformation , Proline/chemistry , StereoisomerismABSTRACT
[reaction: see text] A general, efficient, and experimentally simple method for the generation of sulfenate salts has been developed using beta-sulfinylesters as substrates. The process is based on a retro-Michael reaction, initiated by deprotonation at low temperature. Upon treatment with alkyl halides, the liberated sulfenates are subsequently converted into sulfoxides in good to excellent yield. Extension of the methodology to an unprecedented access to nonracemic sulfoxides by introduction of an enantiopure ligand, (-)-sparteine, is also described.
