Iwan G. Jones

ASYMMETRIC ADDITION OF ORGANOLITHIUM REAGENTS TO IMINES FAVOURING (S)-AMINES

Abstract The praline derived chiral catalyst (5) catalyses the asymmetric addition of organolithium reagents to imines, producing (S)-amines in 37–96% yield and up to 21% enantiomeric excess.

A FACILE APPROACH FOR THE SYNTHESIS OF PSEUDO-PEPTIDES INCORPORATING A (2S, 3R)-2-AMINO-CYCLOPROPANE CARBOXYLIC ACID RESIDUE

Abstract The synthesis of a pseudo-tripeptide 9 and a pseudo-pentapeptide 1 incorporating the conformationally constrained β-amino acid (2S, 3R)-2-amino cyclopropane carboxylic acid is reported. The key steps of the synthesis are the desymmetrisation of cyclopropane 1,2-dicarboxylic anhydride using (S)-proline t-butyl ester followed by a Curtius rearrangement. Subsequent trapping of the isocyanate with (S)-proline t-butyl ester or HN-(S)-Pro-(S)-Phe-(S)-Phe-OMe gave the desired pseudo-peptides. The stereochemistry of the desymmetrisation reaction was determined by X-ray crystallography of the amido-acid.

Desymmetrisation of bicyclic, meso-anhydrides by proline esters

Abstract The desymmetrisation of cyclopropane and cyclopentane derived, bicyclic meso-anhydrides using proline esters provides a versatile approach to the synthesis of enantiomerically pure amido acids which can subsequently be converted into β-amino acid containing peptide analogues.

The use of norbornene derivatives in the synthesis of conformationally constrained peptides and pseudo-peptides

The desymmetrisation ofendo-norborn-5-ene-2,3-dicarboxylic anhydride by proline esters has been used to prepare conformationally constrained pseudo-peptides with two peptide chains parallel to one another. A Curtius rearrangement on the desymmetrication adduct produced the corresponding isocyanate which was used to prepare both a peptide incorporating anendo-2-amino-3-carboxy-norborn-5-ene unit, and a pseudo-peptide with two peptide chains parallel to one another but offset by the presence of a urea unit. The conformational analysis of the resulting peptides was carried out, and the norbornene unit was found to induce the formation of β-turns and parallel β-sheets.

THE SYNTHESIS OF CONFORMATIONALLY CONSTRAINED ANALOGUES OF THE ACE INHIBITOR IDRAPRIL

Abstract A conformationally constrained analogue 3 of the ACE inhibitor Idrapril has been prepared by a five-step synthesis. The key step in the synthesis is the desymmetrization of endo-norborn-5-ene-2,3-dicarboxylic anhydride 4 by reaction with t-butyl (S)-prolinate.

Synthesis and application of ligands for the asymmetric addition of organolithium reagents to imines

Amino acid derived ligands 4d,e are prepared from (S)-valine and (S)-proline respectively, and can be used as chiral ligands during the asymmetric addition of organolithium reagents to N-arylimines. Ligand 4e, which is prepared by two independent routes, is found to induce addition of organolithium reagents to the si-face of the imines, whilst ligand 4d in common with the previously reported catalysts 4a–c induces addition to the re-face of the imines.